WO2018149857A1 - Compounds containing si atoms for optically active devices - Google Patents
Compounds containing si atoms for optically active devices Download PDFInfo
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- WO2018149857A1 WO2018149857A1 PCT/EP2018/053632 EP2018053632W WO2018149857A1 WO 2018149857 A1 WO2018149857 A1 WO 2018149857A1 EP 2018053632 W EP2018053632 W EP 2018053632W WO 2018149857 A1 WO2018149857 A1 WO 2018149857A1
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 107
- 239000000203 mixture Substances 0.000 claims abstract description 24
- -1 diethoxymethylsilyl Chemical group 0.000 claims description 79
- 125000004432 carbon atom Chemical group C* 0.000 claims description 78
- 229920000642 polymer Polymers 0.000 claims description 54
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 230000008569 process Effects 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 239000007943 implant Substances 0.000 claims description 7
- 230000003287 optical effect Effects 0.000 claims description 7
- 229910052710 silicon Inorganic materials 0.000 claims description 7
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
- 125000004001 thioalkyl group Chemical group 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 3
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical class C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 abstract description 10
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 376
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 198
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 196
- 125000005647 linker group Chemical group 0.000 description 33
- 125000001424 substituent group Chemical group 0.000 description 31
- 239000000178 monomer Substances 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 11
- 238000006116 polymerization reaction Methods 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
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- 230000015572 biosynthetic process Effects 0.000 description 9
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- 238000001356 surgical procedure Methods 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 8
- 239000000376 reactant Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
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- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 7
- 239000004926 polymethyl methacrylate Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
- 125000004430 oxygen atom Chemical group O* 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 239000006096 absorbing agent Substances 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 4
- 201000004569 Blindness Diseases 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000004809 Teflon Substances 0.000 description 4
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- 238000013461 design Methods 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 229920001296 polysiloxane Polymers 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 125000005369 trialkoxysilyl group Chemical group 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QWVIHBPMUGBFLE-UHFFFAOYSA-N (2-oxo-3-phenylchromen-7-yl) acetate Chemical class O=C1OC2=CC(OC(=O)C)=CC=C2C=C1C1=CC=CC=C1 QWVIHBPMUGBFLE-UHFFFAOYSA-N 0.000 description 3
- PBKONEOXTCPAFI-UHFFFAOYSA-N 1,2,4-trichlorobenzene Chemical compound ClC1=CC=C(Cl)C(Cl)=C1 PBKONEOXTCPAFI-UHFFFAOYSA-N 0.000 description 3
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 3
- RIPZCQZTVDNJHQ-UHFFFAOYSA-N 7-hydroxy-3-phenylchromen-2-one Chemical class O=C1OC2=CC(O)=CC=C2C=C1C1=CC=CC=C1 RIPZCQZTVDNJHQ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 229960001701 chloroform Drugs 0.000 description 3
- FRZDLTCXOSFHJC-UHFFFAOYSA-N chromene-2-thione Chemical compound C1=CC=C2OC(=S)C=CC2=C1 FRZDLTCXOSFHJC-UHFFFAOYSA-N 0.000 description 3
- 229960000956 coumarin Drugs 0.000 description 3
- 235000001671 coumarin Nutrition 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 238000005227 gel permeation chromatography Methods 0.000 description 3
- 230000009477 glass transition Effects 0.000 description 3
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 3
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 2
- KXZSVYHFYHTNBI-UHFFFAOYSA-N 1h-quinoline-2-thione Chemical group C1=CC=CC2=NC(S)=CC=C21 KXZSVYHFYHTNBI-UHFFFAOYSA-N 0.000 description 2
- IUNJCFABHJZSKB-UHFFFAOYSA-N 2,4-dihydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C(O)=C1 IUNJCFABHJZSKB-UHFFFAOYSA-N 0.000 description 2
- BKNIJDXBGKIPDJ-UHFFFAOYSA-N 3-(2-oxochromen-7-yl)oxypropyl 2-methylprop-2-enoate Chemical compound C1=CC(=O)OC2=CC(OCCCOC(=O)C(=C)C)=CC=C21 BKNIJDXBGKIPDJ-UHFFFAOYSA-N 0.000 description 2
- BBXCJCVRMOIRNE-UHFFFAOYSA-N 5-(2-oxochromen-7-yl)oxypentyl 2-methylprop-2-enoate Chemical compound C1=CC(=O)OC2=CC(OCCCCCOC(=O)C(=C)C)=CC=C21 BBXCJCVRMOIRNE-UHFFFAOYSA-N 0.000 description 2
- NHEQGOQGXSUKMK-UHFFFAOYSA-N 7-hex-5-enoxy-3-phenylchromen-2-one Chemical compound C(CCCC=C)OC1=CC=C2C=C(C(OC2=C1)=O)C1=CC=CC=C1 NHEQGOQGXSUKMK-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
- 239000004971 Cross linker Substances 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229920001400 block copolymer Polymers 0.000 description 2
- 238000005266 casting Methods 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 210000004087 cornea Anatomy 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
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- 230000035876 healing Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000006343 heptafluoro propyl group Chemical group 0.000 description 2
- UIZVMOZAXAMASY-UHFFFAOYSA-N hex-5-en-1-ol Chemical compound OCCCCC=C UIZVMOZAXAMASY-UHFFFAOYSA-N 0.000 description 2
- 238000006459 hydrosilylation reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 2
- 208000018769 loss of vision Diseases 0.000 description 2
- 231100000864 loss of vision Toxicity 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 238000003801 milling Methods 0.000 description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
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- 239000010703 silicon Substances 0.000 description 2
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- VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical group COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- MDYPJPPXVOPUNX-UHFFFAOYSA-N thiochromen-2-one Chemical compound C1=CC=C2SC(=O)C=CC2=C1 MDYPJPPXVOPUNX-UHFFFAOYSA-N 0.000 description 2
- ZOVFLKOKOZVLQC-UHFFFAOYSA-N thiochromene-2-thione Chemical compound C1=CC=C2SC(=S)C=CC2=C1 ZOVFLKOKOZVLQC-UHFFFAOYSA-N 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
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- 230000004393 visual impairment Effects 0.000 description 2
- FMQPBWHSNCRVQJ-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-yl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC(C(F)(F)F)C(F)(F)F FMQPBWHSNCRVQJ-UHFFFAOYSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- IVSQMSIRHKTHCB-UHFFFAOYSA-N 1,3,2,4-diazadisiletidine Chemical class N1[SiH2]N[SiH2]1 IVSQMSIRHKTHCB-UHFFFAOYSA-N 0.000 description 1
- QTKPMCIBUROOGY-UHFFFAOYSA-N 2,2,2-trifluoroethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCC(F)(F)F QTKPMCIBUROOGY-UHFFFAOYSA-N 0.000 description 1
- CLISWDZSTWQFNX-UHFFFAOYSA-N 2,2,3,3,3-pentafluoropropyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCC(F)(F)C(F)(F)F CLISWDZSTWQFNX-UHFFFAOYSA-N 0.000 description 1
- VIEHKBXCWMMOOU-UHFFFAOYSA-N 2,2,3,3,4,4,4-heptafluorobutyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCC(F)(F)C(F)(F)C(F)(F)F VIEHKBXCWMMOOU-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- FEYAPNFQAGLQFM-UHFFFAOYSA-N 3-[4-pentyl-2-(trifluoromethyl)phenyl]-7-(6-triethoxysilylhexoxy)chromen-2-one Chemical compound C(CCCC)C1=CC(=C(C=C1)C=1C(OC2=CC(=CC=C2C=1)OCCCCCC[Si](OCC)(OCC)OCC)=O)C(F)(F)F FEYAPNFQAGLQFM-UHFFFAOYSA-N 0.000 description 1
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- KVLREKCVKPSFCW-UHFFFAOYSA-N 7-(2-oxochromen-7-yl)oxyheptyl 2-methylprop-2-enoate Chemical compound C1=CC(=O)OC2=CC(OCCCCCCCOC(=O)C(=C)C)=CC=C21 KVLREKCVKPSFCW-UHFFFAOYSA-N 0.000 description 1
- WNOXVJLOQDKVHU-UHFFFAOYSA-N 7-(8-trimethoxysilyloctoxy)chromen-2-one Chemical compound C1=CC(=O)OC2=CC(OCCCCCCCC[Si](OC)(OC)OC)=CC=C21 WNOXVJLOQDKVHU-UHFFFAOYSA-N 0.000 description 1
- LTFDTWGHTJDAOH-UHFFFAOYSA-N 7-[6-[diethoxy(methyl)silyl]hexoxy]-3-[4-pentyl-2-(trifluoromethyl)phenyl]chromen-2-one Chemical compound C(C)O[Si](CCCCCCOC1=CC=C2C=C(C(OC2=C1)=O)C1=C(C=C(C=C1)CCCCC)C(F)(F)F)(C)OCC LTFDTWGHTJDAOH-UHFFFAOYSA-N 0.000 description 1
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- MGNZXYYWBUKAII-UHFFFAOYSA-N C1C=CC=CC1 Chemical compound C1C=CC=CC1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 1
- 101100448444 Caenorhabditis elegans gsp-3 gene Proteins 0.000 description 1
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- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
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- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- GAURFLBIDLSLQU-UHFFFAOYSA-N diethoxy(methyl)silicon Chemical compound CCO[Si](C)OCC GAURFLBIDLSLQU-UHFFFAOYSA-N 0.000 description 1
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- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000006606 n-butoxy group Chemical group 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003935 n-pentoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005246 nonafluorobutyl group Chemical group FC(F)(F)C(F)(F)C(F)(F)C(F)(F)* 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 150000002900 organolithium compounds Chemical class 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- 238000011907 photodimerization Methods 0.000 description 1
- 238000005498 polishing Methods 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 238000010526 radical polymerization reaction Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229920005604 random copolymer Polymers 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000013545 self-assembled monolayer Substances 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- LIVNPJMFVYWSIS-UHFFFAOYSA-N silicon monoxide Inorganic materials [Si-]#[O+] LIVNPJMFVYWSIS-UHFFFAOYSA-N 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000004528 spin coating Methods 0.000 description 1
- 229920006301 statistical copolymer Polymers 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical group FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 1
- DIOZFKOOIBATNZ-UHFFFAOYSA-N thiocoumarin Chemical compound C1=CC=C2C(OCCCN(C)C)=CC(=O)SC2=C1 DIOZFKOOIBATNZ-UHFFFAOYSA-N 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 1
- OFHCXWMZXQBQMH-UHFFFAOYSA-N trifluoro(trifluoromethylsulfanyl)methane Chemical compound FC(F)(F)SC(F)(F)F OFHCXWMZXQBQMH-UHFFFAOYSA-N 0.000 description 1
- KPZYAGQLBFUTMA-UHFFFAOYSA-K tripotassium;phosphate;trihydrate Chemical compound O.O.O.[K+].[K+].[K+].[O-]P([O-])([O-])=O KPZYAGQLBFUTMA-UHFFFAOYSA-K 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 238000005757 von Pechmann cycloaddition reaction Methods 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/12—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 3 and unsubstituted in position 7
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
- C08G77/04—Polysiloxanes
- C08G77/22—Polysiloxanes containing silicon bound to organic groups containing atoms other than carbon, hydrogen and oxygen
- C08G77/24—Polysiloxanes containing silicon bound to organic groups containing atoms other than carbon, hydrogen and oxygen halogen-containing groups
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
- C08G77/80—Siloxanes having aromatic substituents, e.g. phenyl side groups
-
- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
- G02B1/04—Optical elements characterised by the material of which they are made; Optical coatings for optical elements made of organic materials, e.g. plastics
-
- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
- G02B1/04—Optical elements characterised by the material of which they are made; Optical coatings for optical elements made of organic materials, e.g. plastics
- G02B1/041—Lenses
- G02B1/043—Contact lenses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/14—Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
- A61F2/16—Intraocular lenses
- A61F2/1613—Intraocular lenses having special lens configurations, e.g. multipart lenses; having particular optical properties, e.g. pseudo-accommodative lenses, lenses having aberration corrections, diffractive lenses, lenses for variably absorbing electromagnetic radiation, lenses having variable focus
- A61F2/1624—Intraocular lenses having special lens configurations, e.g. multipart lenses; having particular optical properties, e.g. pseudo-accommodative lenses, lenses having aberration corrections, diffractive lenses, lenses for variably absorbing electromagnetic radiation, lenses having variable focus having adjustable focus; power activated variable focus means, e.g. mechanically or electrically by the ciliary muscle or from the outside
- A61F2/1627—Intraocular lenses having special lens configurations, e.g. multipart lenses; having particular optical properties, e.g. pseudo-accommodative lenses, lenses having aberration corrections, diffractive lenses, lenses for variably absorbing electromagnetic radiation, lenses having variable focus having adjustable focus; power activated variable focus means, e.g. mechanically or electrically by the ciliary muscle or from the outside for changing index of refraction, e.g. by external means or by tilting
-
- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
- G02B1/04—Optical elements characterised by the material of which they are made; Optical coatings for optical elements made of organic materials, e.g. plastics
- G02B1/041—Lenses
Definitions
- hydrophobic fluorocarbon polymer is known from Jean-Marc technik, J Cataract Refract Surg. 1998, 24, 371 -379. Teflon AF ® (Dupont de
- Xo is O or S
- linker -[B]- are therefore selected from the group of formulae (B-1 ) to (B-34),
- the invention therefore relates additionally to compounds of formula (I), (I- 1 ) and/or (I-2) as described before wherein -[B]- corresponds to formula (1 ) and (2) and Xi, X3 and X 4 are CR' and R' has at each occurrence
- At least two substituents R' are different from H and are independently selected from the group consisting of F, a linear or branched, non-halogenated, partially or completely halogenated alkyl group having 1 to 10 C atoms, a linear or branched hydroxyalkyi group having 1 to 10 C atoms, a linear or branched, non-halogenated and a partially or completely halogenated alkoxy group having 1 to 10 C atoms.
- the invention is therefore additionally directed to compounds of formula (I) wherein n is 1 and m is 1 which can preferably be described according to formula ( ⁇ ),
- s is 1 .
- the total number of repeating units n is preferably > 30, very preferably > 100, most preferably > 200, and preferably up to 5000, very preferably up to 3000, most preferably up to 2000, including any combination of the aforementioned lower and upper limits of n.
- the polymers of the present invention include homopolymers, statistical copolymers, random co-polymers, alternating co-polymers and block copolymers, and combinations of the aforementioned.
- the polymerizable group Ri forms the regioregular, alternated, regiorandom, statistical, block or random homopolymer or co-polymer backbone or is part of the polymer backbone where Ri has a meaning as described or preferably described before.
- such oligomer or polymer comprises a constitutional unit M° of formulae (1 -p-1 ), (1 -p-2), (1 -p-
- the co-polymer may be an oligomer or polymer comprising one or more polymerized compounds of formula (I), (1-1 ), (I-2), ( ⁇ ), (I") or ( ⁇ ") or a constitutional unit M° of formulae (1 -p-1 ) to (1 -p-1 1 ), which may be the same or different from one another, and one or more constitutional units M 2 , which may be the same or different from one another.
- Said one or more constitutional units M 2 are chemically different from the units M°.
- said one or more constitutional units M 2 are derived by polymerization of one or more monomers selected from the group consisting of
- EE is used to denote ethyl acetate.
- THF is used to denote tetrahydrofuran.
- Co-polymer-properties can be investigated on blanks, prepared by bulk polymerization of the monomers. Co-monomers, cross-linkers and initiators therefore can be purchased from commercial sources. All chemicals are of highest purity available and can be used as received.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- General Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Materials For Medical Uses (AREA)
Abstract
The present invention relates to novel 2-oxo-2H-chromen compounds, particularly to compounds comprising a photoactive unit, said novel compounds being particularly suitable for compositions and ophthalmic devices as well as to compositions and ophthalmic devices comprising such compounds.
Description
Compounds containing Si atoms for optically active devices
Field of the Invention
The present invention relates to novel compounds, particularly to
compounds comprising a photoactive unit, said novel compounds being particularly suitable for compositions and ophthalmic devices as well as to compositions and ophthalmic devices comprising such compounds.
Background of the Invention
Cataract is a general term for an affection of the eye that leads to a loss of vision and in the extreme to blindness by clouding of the normally clear lens of the eye. It is the major cause of blindness in the world, affecting more than 100 million people. Due to the fact that its major cause is age and the population's average age is increasing, it is expected that the number of cataracts will continue to increase substantially in the future.
Effective treatment of cataract is only possible by surgical intervention, whereby the natural lens of the eye is removed through an incision in the cornea and replaced with an artificial lens, often also referred to as
"intraocular lens". In preparation of surgery current state-of-the-art surgical methods employ eye mapping so as to approximate the refractive power best suited to the respective patient.
Even though cataract surgery is one of the most widely used and safest surgical procedures it is not without specific post-surgery problems. It frequently happens that the refractive power of the implanted intraocular lens (IOL) is insufficient for restoring good vision. Such problems may, for example, be caused by changes in eye geometry as consequence of the surgery as well as irregular wound healing and positioning errors that result in the artificial lens not having the optimal optical properties. As a result the patient will still require corrective vision aids, e.g. glasses, to be able to see correctly. In some cases the resulting refractive power of the implanted
artificial lens is so far removed from the required refractive power that further surgery will be required. Particularly for aged persons this is not desirable because the body's capability for healing is reduced with increasing age. Furthermore, there is the risk of attracting endophthalmitis, an inflammation of the eye, which can even lead to a complete loss of vision or worse, loss of the eye.
There is therefore a need in the health sector for optically active devices, and particularly artificial intraocular lenses, that would allow for non- invasive adjustment of refractive power after implantation of the lens, thereby preferably further reducing the need for post-surgery vision aids.
Some developments in this sense have already been made, as for example evidenced by WO 2007/033831 A1 , WO 2009/074520 A2 or US
20100324165 A1 corresponding to WO 2009/074521 A1 .
WO 2009/074521 A1 describes ophthalmological compositions comprising coumarin acrylates or methacrylates. Suratwala et al, Journal of Sol-Gel Science and Technology 1997, 8, 973- 978 describe silylated coumarin dyes in polyceram hosts forming crack free, polishable monoliths.
WO 2006/078834 A1 describes heterocyclic benzo[c]chromene derivatives useful as modulators of the estrogen receptors.
J. Trager et al, describes polymers for in vivo tuning of refractive properties in intraocular lenses such as homopolymers comprising polymerized 7-(3- methacryloyloxypropoxy)coumarin (MAOC-C3) being slightly opaque and having a Tg of 76°C, homopolymers comprising polymerized 7-(5- methacryloyloxypentoxy)coumarin (MAOC-C5) being transparent and having a Tg of 52°C and homopolymers comprising polymerized 7-(7-
methacryloyloxyheptoxy)counnarin (MAOC-C7) being transparent and having a Tg of 45°C.
M. Schraub et al, European Polymer Journal 49 (2013), 1714-1721 describes high refractive index coumarin-based photorefractive
polysiloxanes.
M. Schraub et al, European Polymer Journal 51 (2014) 21 -27 describes the photochemistry of 3-phenyl-coumarin containing polymethacrylates.
Siegel et al., J. Am. Chem. Soc, (1998), 120, 9680-9681 describes the synthesis of bifunctional photorefractive polymers with net gain.
Qin et al., Polymer International 48, (1999), 491 -494 describes the synthesis and structural characterization of novel multifunctional polysiloxanes having photo-refractive properties.
Shashidhar et al, J. Mater. Chem. (2001 ), 1 1 , 2992-2995 describes the synthesis and photodimerization in self-assembled monolayers of 7-(8- trimethoxysilyloctyloxy)coumarin.
Poly(methyl methacrylate) (PMMA) intraocular lenses (lOLs) that were coated with Teflon AF®, an amorphous, transparent, and highly
hydrophobic fluorocarbon polymer is known from Jean-Marc Legeais, J Cataract Refract Surg. 1998, 24, 371 -379. Teflon AF® (Dupont de
Nemours) is a poly(tetra-fluoroethylene co-hexafluoro-propyl-2
cyclodethoxydifluoroethylene). Constituted entirely of high-energy bonds, it is stable at temperatures up to 260°C and chemically very resistant. The refractive index is 1 .32. It transmits light from 200 to 2000 nm with a constant light absorption below 5%. The contact angle with water is 129 degrees. The surface modification is described using a PMMA IOL (model 808A, Kabi Pharmacia Production B.V.) having an overall diameter of 12.0
mm and optic diameter of 6.5 mm which is coated by immersing the lense in a 5% solution of Teflon AF in a fluorocarbon solvent (CsFis) for 3 seconds and then placing it at a temperature of 37°C to evaporate the solvent. As a result, the surface of the PMMA IOL was completely coated with Teflon AF.
Eun-Ho Sohn et al describe surface properties of poly(methyl methacrylate) (PMMA) films using poly(perfluoromethyl methacrylate)s (PFMMAs) with short perfluorinated side chains. 2,2,2-Trifluoroethyl methacrylate,
1 ,1 ,1 ,3,3,3-hexafluoroisopropyl methacrylate, 2,2,3,3,3-pentafluoropropyl methacrylate, 2,2,3,3,4,4,4-heptafluorobutyl methacrylate were prepared by radical polymerization of the corresponding monomers. Film preparation is reported with PMMA, PFMMA and their blends. However, the compounds disclosed therein suffer from being too stiff and too brittle so that they can't be rolled or folded and are thus not fit to be implanted by state of the art cataract surgical methods, particularly by state of the art micro-incision cataract surgical methods. Consequently, it is an objective of the present application to provide for novel compounds suitable for ophthalmic devices.
It is also an objective of the present application to provide for compounds, the optical properties of which may be changed, preferably by non-invasive techniques.
It is a further objective of the present application to provide for novel compounds having advantages over currently known compounds, preferably in combination with being suitable for ophthalmic devices.
Advantages such as better flexibility and objectives of the compounds of the present application will be evident to the skilled person from the following detailed description as well as from the examples.
Summary of the Invention
The present inventors have found that the above objects may be attained either individually or in any combination by the compounds and ophthalmic devices of the present application. The invention relates to compounds of formula (I)
wherein
X is O, S or NRo,
Xo is O or S,
Y is O, S or a bond,
n is 0 or 1 ,
m is 0 or 1 ,
n+m is 1 or 2,
-[B]- is selected from the group consisting of formula (1 ) to formula (4),
Xi, X2, X3, X4 are each independently of each other CR' or N,
X5 is each independently O, S, C=O or NRo,
Χ6, X7 are each independently CR' or N,
R is at each occurrence independently selected from the group consisting of H, F, a linear or branched alkyl group having 1 to 4 C atoms or a linear or branched partially or fully fluorinated alkyl group having 1 to 4 C atoms,
R' is at each occurrence independently selected from the group consisting of H, F, a linear or branched, non- halogenated, partially or completely halogenated alkyl group having 1 to 20 C atoms, a linear or branched hydroxyalkyl group having 1 to 20 C atoms, a non- halogenated, partially or completely halogenated cycloalkyl group having 3 to 6 C atoms, a linear or branched, non-halogenated, partially or completely halogenated alkoxy group having 1 to 20 C atoms, a linear or branched, non-halogenated, partially or completely halogenated thioalkyl group having 1 to 20 C atoms,
Ro is at each occurrence independently selected from the group consisting of a linear or branched alkyl group having 1 to 10 C atoms or a cycloalkyl group having 3 to 6 C atoms,
Ri is a polymerizable group containing at least one Si atom,
-R2- is -(C(R)2)o-,
-(C(R)2)p-X8-(C(R)2)q-(X9)s-(C(R)2)^(Xio)t-(C(R)2)u- or
a cycloalkylene group having 5 or 6 C atoms which can be substituted with at least one R which is different from H,
o is selected from the group consisting of 1 to 20,
Xs, X9, X10 are at each occurrence independently O, S or NRo, s, t is O or l ,
p, q are at each occurrence independently selected from the group consisting of 1 to 10,
r, u are at each occurrence independently selected from the group consisting of 0 to 10, wherein the overall number of atoms for -(C(R)2)p-X8-(C(R)2)q-(X9)s-(C(R)2)^(Xio)t-
(C(R)2)u- is up to 20 atoms,
R3, R4, R5, R6 are at each occurrence independently R',
R7 is R' in case m is 0 and
R7 is Ri in case m is 1 .
Preferably, the substituent [Ri-R2-Y]n is bonded in position 7 or 6 of the heterocyclus. Particularly preferably, the substituent [Ri-R2-Y]n is bonded in position 7 of the heterocyclus. Such compounds are represented by formula (1-1 ) and (I-2)
wherein Ri, -R2-, Y, n, R3, R4, R5, R6, R7, X, Xo, m and [B] have a meaning as described before.
The invention relates further to compositions comprising at least one of said compounds of formula (I) and/or their polymerized forms as well as to articles comprising at least one polymerized compound of formula (I).
In addition, the invention relates to a process for forming such article, said process comprising the steps of
- providing a composition comprising at least one compound of formula (I) and/or an oligomer or polymer as described before;
subsequently forming the article of said composition.
Furthermore, the invention relates to a process for changing the optical properties of an article according to the invention, said process comprising the steps of
- providing an article comprising at least one polymerized compound of formula (I), and
- subsequently exposing said article to irradiation having a wavelength of at least 200 nm and at most 1500 nm. Detailed Description of the Invention
The compounds of formula (I) and all preferred embodiments of compounds of formula (I) according to the present invention include all stereoisomers or racemic mixtures.
The compounds of formula I provide several advantages over prior art materials
- by choosing a Si containing polymer backbone they show comparably lower glass transition points than polymers based on acrylate or
methacrylate thus becoming better foldable or bendable;
- by adding a linker -[B]- to the 1 -benzopyran-2-one, 1 -benzopyran-2- thione, thiochromene-2-one, thiochromene-2-thione, quinolin-2-one or
quinolin-2-thione ring system their refrective index will increase and UV stability is further enhanced;
- by incorporating at least one F atom or at least one partially or fully fluorinated alkyl group they develop a non-sticky behavior with
characteristic surfactant properties; through their non-stickiness the compounds also show a smoother behavior in a physiological environment.
Homopolymers comprising polymerized 7-(3- methacryloyloxypropoxy)coumarin are slightly opaque and have a Tg of 76°C; homopolymers comprising polymerized 7-(5- methacryloyloxypentoxy)coumarin are transparent and have a Tg of 52°C and homopolymers comprising polymerized 7-(7- methacryloyloxyheptoxy)coumarin are transparent and have a Tg of 45°C. In comparison to known acrylate and methacrylate polymer backbones, compounds according to the invention are more stable toward UV- irradiation due to higher stability of the Si-O or Si-N bond.
Polymers that are foldable at room temperature generally exhibit glass transition temperatures (Tg) lower than room temperature (ca. 21 °C). They are easily deformable at this temperature without causing physical damage to the polymer, for example by inducing creep, stress or fissures. For polymers in intraocular lenses, Tgs of less than or equal to 15 °C are preferred.
Polymers used in intraocular lens manufacturing have preferably relative high refractive indices, which enable the fabrication of thinner intraocular lenses. Preferably, the polymer used in an intraocular lens will have a refractive index greater than about 1 .5 and presently most preferably greater than about 1 .55.
In case an asterisk ("*") is used within the description of the present invention, it denotes a linkage to an adjacent unit or group or, in case of a polymer, to an adjacent repeating unit or any other group. A linear or branched alkyi group having 1 to 10 C atoms denotes an alkyi group having 1 , 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms, for example methyl, ethyl, /'so-propyl, n-propyl, /'so-butyl, n-butyl, terf-butyl, n-pentyl, 1 -, 2- or 3-methylbutyl, 1 ,1 -, 1 ,2- or 2,2-dimethylpropyl, 1 -ethylpropyl, n-hexyl, n- heptyl, n-octyl, ethylhexyl, n-nonyl or n-decyl. A linear or branched alkyi group having 1 to 20 C atoms include all examples for a linear or branched alkyi group having 1 to 10 C atoms including any alkyi group having 1 1 , 12, 13, 14, 15, 16, 17, 18, 19 and 20 C atoms such as n-undecyl, n-dodecyl, n- tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n-nonadecyl and n-eicosyl.
The term partially halogenated alkyi group denotes that at least one H atom of the alkyi group is replaced by F, CI, Br or I. Preferably, the alkyi group is partially fluorinated meaning that at least one H atom of the alkyi group is replaced by F.
The term completely halogenated alkyi group denotes that all H atoms of the alkyi group are replaced by F, CI, Br and/or I. Preferably, the alkyi group is completely fluorinated meaning that all H atoms of the alkyi group are replaced by F. A preferred completely fluorinated alkyi group is
trifluoromethyl.
The term halogenated or preferably fluorinated corresponds additionally to other groups such as a halogenated cycloalkyl group, a halogenated alkoxy group or a halogenated thioalkyl group.
A linear or branched hydroxyalkyi group having 1 to 20 C atoms denotes an alkyi group having 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18,
19 or 20 C atoms wherein at least one H atom is replaced by a hydroxyl group (-OH). The hydroxyl group is preferably replaced on the last C atom of the alkyl group, for example hydroxymethyl, 2-hydroxyethyl, 3-hydroxy- propyl, 4-hydroxy-butyl, 5-hydroxy-pentyl, 4-hydroxy-1 -, - 2- or -3-methylbutyl, 3-hydroxy-1 ,1 -, -1 ,2- or -2,2-dimethylpropyl, 3-hydroxy- 1 -ethylpropyl, 6-hydroxy-hexyl, 7-hydroxy-heptyl, 8-hydroxy-octyl, 6- hydroxy-1 -ethylhexyl, 9-hydroxy-nonyl, 10-hydroxy-decyl, 1 1 -hydroxy- undecyl, 12-hydroxy-dodecyl, 13-hydroxy-tridecyl, 14-hydroxy-tetradecyl, 15-hydroxy-pentadecyl, 16-hydroxy-hexadecyl, 17-hydroxy-heptadecyl, 18- hydroxy-octadecyl, 19-hydroxy-nonadecyl and 20-hydroxy-eicosyl.
Preferred hydroxyalkyl groups are hydroxymethyl and 3-hydroxy-propyl.
A cycloalkyl group having 3 to 6 C atoms includes cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl which may be partially or completely
halogenated or fluorinated as explained before.
A linear or branched alkoxy group having 1 to 20 C atoms denotes an
0- alkyl group having 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19 or 20 C atoms, for example methoxy, ethoxy, /so-propoxy, n- propoxy, /'so-butoxy, n-butoxy, terf-butoxy, n-pentyloxy, 1 -, 2- or
3-methylbutyloxy, 1 ,1 -, 1 ,2- or 2,2-dimethylpropoxy, 1 -ethyl propoxy, n- hexyloxy, n-heptyloxy, n-octyloxy, ethylhexyloxy, n-nonyloxy, n-decyloxy, n- undecyloxy, n-dodecyloxy, n-tridecyloxy, n-tetradecyloxy, n-pentadecyloxy, n-hexadecyloxy, n-heptadecyloxy, n-octadecyloxy, n-nonadecyloxy and n- eicosyloxy which may be partially or completely halogenated or preferably may be partially or completely fluorinated. A preferred completely
fluorinated alkoxy group is trifluoromethoxy.
A linear or branched thioalkyl group having 1 to 20 C atoms denotes a S-alkyl group having 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19 or 20 C atoms, for example thiomethyl, 1 -thioethyl, 1 -thio-/so-propyl,
1 - thio-n-propoyl, 1 -thio-/so-butyl, 1 -thio-n-butyl, 1 -th io-ierf-butyl , 1 -th io-n-
pentyl, 1 -thio-1 -, -2- or -3-methylbutyl, 1 -thio-1 ,1 -, -1 ,2- or -2,2- di methyl propyl, 1 -th io- 1 -ethyl propyl , 1 -thio-n-hexyl, 1 -thio-n-heptyl, 1 -thio-n- octyl, 1 -thio-ethylhexyl, 1 -thio-n-nonyl, 1 -thio-n-decyl, 1 -thio-n-undecyl, 1 - thio-n-dodecyl, 1 -thio-n-tridecyl, 1 -thio-n-tetradecyl, 1 -thio-n-pentadecyl, 1 - thio-n-hexadecyl, 1 -thio-n-heptadecyl, 1 -thio-n-octadecyl, 1 -thio-n- nonadecyl and 1 -thio-n-eicosyl which may be partially or completely halogenated or preferably may be partially or completely fluorinated. A preferred completely fluorinated thioether group is trifluoromethyl thioether. Preferred alkyl and alkoxy radicals have 1 , 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms.
A polymerisable group is a group which can be subject to or can undergo polymerization thus forming an oligomer or a polymer. The polymerizable group is generally not restricted within the invention but contains at least one Si atom.
Polymerization is the process of taking individual monomers and chaining them together to make longer units. These longer units are called polymers. The compounds of formula (I), (1-1 ) and/or (I-2) as described before and preferably described below are suitable monomers.
Within the gist of the invention, the polymerizable group Ri once
oligomerized or polymerized thus forms or is part of the backbone of the oligomer or polymer comprising polymerized compounds of formula (I), (1-1 ) and/or (I-2). The polymerizable groups Ri contain silicon thus forming polysiloxanes or polysilazanes and will be described further below.
The linker -[B]- is selected from the group of formulae (1 ) to (4), wherein Xi, X2, X3, X are each independently of each other CR' or N, X5 is each independently O, S, C=O or NRo and X6 and X7 are each independently CR'
or N, wherein R' and Ro have a meaning as described before or preferably described below.
Preferred examples for the linker -[B]- are therefore selected from the group of formulae (B-1 ) to (B-34),
wherein R' and Ro have a meaning as described before or preferably described below.
Compounds of fornnula (I), (1-1 ) and/or (I-2) as described before are preferred where the linker -[B]- corresponds to fornnula (1 ) or (2) and Χι, X2, X3 and X4 have a meaning as described before. Therefore, compounds of formula (I), (1-1 ) and/or (I-2) are preferred where the linker -[B]- corresponds to formulae (B-1 ) to (B-19).
The invention therefore relates additionally to compounds of formula (I), (I- 1 ) and/or (I-2) as described before wherein -[B]- corresponds to formula (1 ) and (2) and Xi, X2, X3 and X4 have a meaning as described before.
Compounds of formula (I), (1-1 ) and/or (I-2) as described before are particularly preferred where the linker -[B]- corresponds to formula (1 ) or (2) and Xi, X3 and X4 are CR' and R' has at each occurrence independently a meaning as described before or preferably described below. Therefore, compounds of formula (I), (1-1 ) and/or (I-2) are particularly preferred where the linker -[B]- corresponds to formulae (B-1 ), (B-3), (B-8) or (B-9).
The invention therefore relates additionally to compounds of formula (I), (I- 1 ) and/or (I-2) as described before wherein -[B]- corresponds to formula (1 ) and (2) and Xi, X3 and X4 are CR' and R' has at each occurrence
independently a meaning as described before or preferably described below. Compounds of formula (I), (1-1 ) and/or (I-2) as described or preferably described before are especially preferred where the linker -[B]- corresponds to formula (1 ) or (2) and X2 is CR' and R' has at each occurrence
independently a meaning as described before or preferably described below. Therefore, compounds of formula (I), (1-1 ) and/or (I-2) are especially preferred where the linker -[B]- corresponds to formulae (B-1 ), (B-2), (B-6), (B-7), (B-8), (B-10) or (B-1 1 ). Additionally, compounds of formula (I), (1-1 ) and/or (I-2) having a linker -[B]- which corresponds to formula (B-1 ) or (B-8)
are very particularly preferred and R' has at each occurrence independently a meaning as described before or preferably described below. Within this very particular preferred compounds of formula (I), (1-1 ) and/or (I-2), it is preferred to select the linker of formula (B-1 ) and R' has at each occurrence independently a meaning as described before or preferably described below.
The invention therefore relates additionally to compounds of formula (I), (I- 1 ) and/or (I-2) as described or preferably described before wherein -[B]- corresponds to formula (1 ) and (2) and X2 is CR' and R' has at each occurrence independently a meaning as described before or preferably described below.
R' is at each occurrence independently selected from the group consisting of H, F, a linear or branched, non-halogenated, partially or completely halogenated alkyl group having 1 to 20 C atoms, a linear or branched hydroxyalkyl group having 1 to 20 C atoms, a non-halogenated, partially or completely halogenated cycloalkyl group having 3 to 6 C atoms, a linear or branched, non-halogenated, partially or completely halogenated alkoxy group having 1 to 20 C atoms, a linear or branched, non-halogenated, partially or completely halogenated thioalkyi group having 1 to 20 C atoms. It is preferred that at least one R' in -[B] as described before or preferably described before is different from H and is selected from the group consisting of F, a linear or branched, non-halogenated, partially or completely halogenated alkyl group having 1 to 20 C atoms, a linear or branched hydroxyalkyl group having 1 to 20 C atoms, a non-halogenated, partially or completely halogenated cycloalkyl group having 3 to 6 C atoms, a linear or branched, non-halogenated, partially or completely halogenated alkoxy group having 1 to 20 C atoms, a linear or branched, non- halogenated, partially or completely halogenated thioalkyi group having 1 to 20 C atoms. It is particularly preferred that at least two substituents R' are different from H and are independently selected from the group consisting
of F, a linear or branched, non-halogenated, partially or completely halogenated alkyl group having 1 to 20 C atoms, a linear or branched hydroxyalkyi group having 1 to 20 C atoms, a non-halogenated, partially or completely halogenated cycloalkyl group having 3 to 6 C atoms, a linear or branched, non-halogenated, partially or completely halogenated alkoxy group having 1 to 20 C atoms, a linear or branched, non-halogenated, partially or completely halogenated thioalkyl group having 1 to 20 C atoms.
With regard to said substituent R', R' is at each occurrence independently preferably selected from the group consisting of H, F, a linear or branched, non-halogenated, partially or completely halogenated alkyl group having 1 to 10 C atoms, a linear or branched hydroxyalkyi group having 1 to 10 C atoms, a linear or branched, non-halogenated and a partially or completely halogenated alkoxy group having 1 to 10 C atoms.
It is preferred that at least one R' in -[B]- as described before or preferably described before is different from H and is selected from the group consisting of F, a linear or branched, non-halogenated, partially or completely halogenated alkyl group having 1 to 10 C atoms, a linear or branched hydroxyalkyi group having 1 to 10 C atoms, a linear or branched, non-halogenated and a partially or completely halogenated alkoxy group having 1 to 10 C atoms.
It is particularly preferred that at least two substituents R' are different from H and are independently selected from the group consisting of F, a linear or branched, non-halogenated, partially or completely halogenated alkyl group having 1 to 10 C atoms, a linear or branched hydroxyalkyi group having 1 to 10 C atoms, a linear or branched, non-halogenated and a partially or completely halogenated alkoxy group having 1 to 10 C atoms.
R' is at each occurrence independently particularly preferably selected from the group consisting of H, F, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n- hexyl, n-heptyl, n-octyl, trifluormethyl, pentafluorethyl, heptafluorpropyl,
methoxy, ethoxy, propoxy, trifluormethoxy, pentafluorethoxy, 2-hydroxy- ethyl, 3-hydroxy-propyl, 4-hydroxy-butyl and 5-hydroxy-pentyl.
R' is at each occurrence independently very particularly preferably selected from the group consisting of H, F, ethyl, n-pentyl, trifluoromethyl, methoxy and trifluoromethoxy.
Therefore, the invention is further directed to compounds of formula (I), (1-1 ) and/or (I-2) as described before where -[B]- corresponds to formulae (1 ) to (4) and wherein at least one R' within Xi, X2, X3. X4, ΧΘ or X7 is not H.
Therefore, the invention is further directed to compounds of formula (I), (1-1 ) and/or (I-2) as described before where -[B]- corresponds to formulae (B-1 ) to (B-29) or (B-31 ) to (B-34) or to preferred linkers as described before, wherein at least one R' is not H and Ro have a meaning as described before or preferably described below.
The substituent R' within Xi or X3 in formula (1 ) is particularly preferred not H and has a meaning as described before.
The substituent R' within X7 in formula (3) is particularly preferred not H and has a meaning as described before.
As described before, the substituents R3, R4, R5 and R6 are at each occurrence independently R' where R' has at each occurrence
independently a meaning or a preferred or particularly preferred meaning as described before.
R5 is preferably H or F. R5 is particularly preferably H.
As described before, the substituent R7 corresponds to R' in case m is 0 wherein R' has a meaning or a preferred or particularly preferred meaning as described before. Preferably in case m is 0, R7 corresponds to R' which is not H and has a meaning as described before.
In all cases when R' is preferably not H, it is selected from the preferred group consisting of F, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n- heptyl, n-octyl, trifluoromethyl, pentafluoroethyl, heptafluoropropyl, methoxy, ethoxy, propoxy, trifluoromethoxy, pentafluoroethoxy, 2-hydroxy- ethyl, 3-hydroxy-propyl, 4-hydroxy-butyl and 5-hydroxy-pentyl or from the particular preferred group consisting of F, ethyl, n-pentyl, trifluoromethyl, methoxy and trifluoromethoxy. Therefore, the invention is further directed to compounds of formula (I), (1-1 ) and/or (I-2) as described before where -[B]- corresponds to formulae (1 ) to (4) and wherein at least one R' within Xi, X2, X3. X4, ΧΘ or X7 is not H and R7 is not H in case m is 0. Therefore, the invention is further directed to compounds of formula (I), (1-1 ) and/or (I-2) as described before where -[B]- corresponds to formulae (B-1 ) to (B-29) or (B-31 ) to (B-34) or to preferred linkers as described before, wherein at least one R' is not H and R7 is not H in case m is 0 and Ro has a meaning as described before or as preferably described below.
As described before, the substituent R7 corresponds to Ri in case m is 1 wherein Ri has a meaning or a preferred meaning as described before or further below. Compounds of formula (I), (1-1 ) and/or (I-2) in which m is 1 are preferred having a linker -[B]- selected from the group consisting of formula (1 ) to (4) wherein at least one substituent R' within Xi, X2, X3, X4, ΧΘ or X7 is not H and in which at least one substituent R3, R4 or R6 is not H.
Therefore, the invention is further directed to compounds of formula (I), (1-1 ) and/or (I-2) as described before where -[B]- corresponds to formulae (1 ) to (4) and wherein at least one R' within Xi, X2, X3. X4, ΧΘ or X7 is not H, in which at least one substituent R3, R4 or R6 is not H and R7 corresponds to Ri in case m is 1 .
Therefore, the invention is further directed to compounds of formula (I), (1-1 ) and/or (I-2) as described before where -[B]- corresponds to formulae (B-1 ) to (B-29) or (B-31 ) to (B-34) or to preferred linkers as described before, wherein at least one R' is not H, in which at least one substituent R3, R4 or R6 is not H and R7 corresponds to Ri in case m is 1 wherein Ro and Ri has a meaning as described before or further below.
Compounds of formula (I), (1-1 ) and/or (I-2) with linkers -[B]- as defined before or preferably defined before with the described or preferred substitution pattern on the linker -[B]- and its substituents R3, R4, Rs and R6 as described before or preferably described before are based on a 1 - benzopyran-2-one ring system (coumarin or chromene-2-one) in case both X and Xo are O.
Compounds of formula (I), (1-1 ) and/or (I-2) with linkers -[B]- as defined before or preferably defined before with the described or preferred substitution pattern on the linker -[B]- and its substituents R3, R4, Rs and R6 as described before or preferably described before are based on a 1 - benzopyran-2-thione ring system (thiocoumarin or chromene-2-thione) in case X is O and Xo is S.
Compounds of formula (I), (1-1 ) and/or (I-2) with linkers -[B]- as defined before or preferably defined before with the described or preferred substitution pattern on the linker -[B]- and its substituents R3, R4, Rs and R6 as described before or preferably described before are based on a thiochromene-2-one ring system in case X is S and Xo is O.
Compounds of formula (I), (1-1 ) and/or (I-2) with linkers -[B]- as defined before or preferably defined before with the described or preferred substitution pattern on the linker -[B]- and its substituents R3, R4, Rs and R6
as described before or preferably described before are based on a thiochromene-2-thione ring in case both X and Xo are S.
Connpounds of formula (I), (1-1 ) and/or (I-2) with linkers -[B]- as defined before or preferably defined before with the described or preferred substitution pattern on the linker -[B]- and its substituents R3, R4, Rs and R6 as described before or preferably described before are based on a quinolin- 2-one ring system in case X is NRo and Xo is O and Ro is independently selected from the group consisting of a linear or branched alkyl group having 1 to 10 C atoms or a cycloalkyl group having 3 to 6 C atoms.
Compounds of formula (I), (1-1 ) and/or (I-2) with linkers -[B]- as defined before or preferably defined before with the described or preferred substitution pattern on the linker -[B]- and its substituents R3, R4, Rs and R6 as described before or preferably described before are based on a quinolin- 2-thione ring system in case X is NRo and Xo is S and Ro is independently selected from the group consisting of a linear or branched alkyl group having 1 to 10 C atoms or a cycloalkyl group having 3 to 6 C atoms. Ro is at each occurrence independently preferably methyl, ethyl, /'so-propyl, 2-methyl-propyl, n-butyl, n-pentyl, 4-methyl-pentyl or cyclopropyl.
In case X is NRo, Ro is particularly preferably ethyl, /'so-propyl, 2-methyl- propyl, n-pentyl or 4-methyl-pentyl.
In case Xs is NRo, Ro is particularly preferably methyl or n-butyl.
In case Xs, X9 or X10 is NRo, Ro is particularly preferably methyl.
Compounds of formula (I), (1-1 ) and/or (I-2) with linkers and substituents as described before or preferably described before or below are preferred when X is O or S.
Compounds of fornnula (I), (1-1 ) and/or (I-2) with linkers and substituents as described before or preferably described before or below are particularly preferred when Xo is O and X is O or S. Connpounds of fornnula (I), (1-1 ) and/or (I-2) with linkers and substituents as described before or preferably described before or below are very particularly preferred when X is O and Xo is O.
In one preferred embodiment of the invention, the compounds of formula (I), (1-1 ) and/or (I-2) as described before or preferably described before contain one polymerizable group Ri . This is the case for compounds of formula (I), (1-1 ) and/or (I-2) in which n is 1 or m is 1 and the sum of n and m is 1 . Such compounds can be preferably used as monomers for the preparation of a blank which may be transformed to an ophthalmic device such as an eye-implant or specifically an intraocular lens or to the ophthalmic device as such as described before.
The invention is therefore additionally directed to compounds of formula (I) wherein n is 1 and m is 0 which can preferably be described according to formula (l'),
wherein Ri, -R2-, Y, R3, R4, R5, R6, X, Xo, -[B]- and R7 have a meaning as described before or preferably described before or below.
The invention is therefore additionally directed to compounds of formula (I) wherein n is 0 and m is 1 which can preferably be described according to formula (I"),
wherein Ri, -R2-, Y, R3, R4, R5, R6, X, Xo, -[B]- and R7 have a meaning as described before or preferably described before or below.
In another preferred embodiment of the invention, the compounds of formula (I) as described before or preferably described before contain two polymerizable groups Ri . This is the case for compounds of formula (I) in which n is 1 and m is 1 and the sum of n and m is 2. Such compounds can be preferably used as cross-linking agent for the preparation of a blank which may be transformed to an ophthalmic device such as an eye-implant or specifically an intraocular lens or to the ophthalmic device as such as described before.
The invention is therefore additionally directed to compounds of formula (I) wherein n is 1 and m is 1 which can preferably be described according to formula (Π),
wherein Ri, -R2-, Y, R3, R4, R5, R6, X, Xo, -[B]- and R7 have a meaning as described before or preferably described before or below.
Compounds of formula (I), (1-1 ), (I-2) (Γ), (I") and (Γ) with linkers -[B]- and substituents as described before or preferably described before have a
polymerizable group as described before or preferably described before or below and have at least one linking element Y-R2-.
Y is at each occurrence independently O, S or a bond. Y is preferably O. The linking element -R2- is selected from the group consisting of -(C(R)2)o-, -(C(R)2)p-X8-(C(R)2)q-(X9)s-(C(R)2)^(Xio)t-(C(R)2)u- and a cycloalkylene group having 5 or 6 C atoms which is substituted with at least one R which is different from H and o is selected from the group consisting of 1 to 20, Xs, X9 and X10 are at each occurrence O, S or NRo, s and t are at each occurrence independently 0 or 1 , p and q are at each occurrence
independently selected from the group consisting of 1 to 10, r and u are at each occurrence independently selected from the group consisting of 0 to 10, wherein the overall number of atoms for -(C(R)2)P-X8-(C(R)2)q-(X9)s- (C(R)2)^(Xio)t-(C(R)2)u-, is up to 20 C atoms.
R is at each occurrence independently selected from the group consisting of H, F, a linear or branched alkyl group having 1 to 8 C atoms or a linear or branched partially or fully fluorinated alkyl group having 1 to 4 C atoms. R is preferably at each occurrence independently selected from the group consisting of H, F, methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl, isobutyl, ethylhexyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 2,2,3,3,3- pentafluoropropyl, trifluoromethyl, pentafluoroethyl, heptafluoropropyl and nonafluorobutyl. R is particularly preferably at each occurrence
independently H, F, methyl, 2,2,2-trifluoroethyl or trifluoromethyl. R is very particularly preferably at each occurrence independently H or F.
Preferably, o is selected from the group consisting of 6 to 12.
Preferably, s is 1 .
Preferably t is 0 or 1 .
Preferably, Xs, X9 and X10 are O.
Preferably, p and u are each independently 1 , 3, 3, 4, 5 or 6, particularly preferably 1 or 2.
Preferably, q and r are each independently 1 , 2 or 3, particularly preferably 1 .
Suitable examples for -R2- are
-(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH2)8-, -(CH2)9-, - (CH2)io-, -(CH2)ii-, -(CH2)i2-, -(CH2)i3-, -(CH2)i4-, -(CH2)is-, -(CH2)i6-, - (CH2)i7-, -(CH2)i8-, -(CH2)i9-, -(CH2)20-, -(CHCH3)3-, -(CHCH3)4-, -(CHCH3)5- , -(CHCH3)6-, -(CHCH3)7-, -(CHCH3)8-, -(CHCH3)9-, -(CHCH3)io-, - (CHCH3)ii-, -(CHCH3)i2-, -(CHCH3)i3-, -(CHCH3)i4-, -(CHCH3)i5-, - (CHCH3)i6-, -(CHCH3)i7-, -(CHCH3)i8-, -(CHCH3)i9-, -(CHCH3)20- , -(C(CH3)2)2-, -(C(CH3)2)3-, -(C(CH3)2)4-, -(C(CH3)2)5-, -(C(CH3)2)6- , -(C(CH3)2)7-, -(C(CH3)2)8-, -(C(CH3)2)9-, -(C(CH3)2)io-, -(C(CH3)2)n- , -(C(CH3)2)i2-, -(C(CH3)2)i3-, -(C(CH3)2)i4-, -(C(CH3)2)i5-, -(C(CH3)2)i6- , -(C(CH3)2)i7-, -(C(CH3)2)i8-, -(C(CH3)2)i9-, -(C(CH3)2)20-, -(CHC2H5)2-, - (CHC2H5)3-, -(CHC2H5)4-, -(CHC2H5)5-, -(CHC2H5)6-, -(CHC2H5)7-, - (CHC2H5)8-, -(CHC2H5)9-, -(CHC2H5)io-, -(CHC2H5)n-, -(CHC2H5)i2-, - (CHC2H5)i3-, -(CHC2H5)i4-, -(CHC2H5)i5-, -(CHC2H5)i6-, -(CHC2H5)i7-, - (CHC2H5)i8-, -(CHC2H5)i9-, -(CHC2H5)20-, -(CH2)-(CHCH3)-(CH2)-, -(CH2)- (CHCH3)-(CH2)2-, -(CH2)-(CHCH3)-(CH2)3-, -(CH2)-(CHCH3)-(CH2)n-, - (CH2)2-(CHCH3)-(CH2)-, -(CH2)3-(CHCH3)-(CH2)-, -(CH2)n-(CHCH3)-(CH2)-, -(CH2)2-O-(CH2)2-, -(CH2)3-O-(CH2)3-, -(CH2)2-O-(CH2)2-O-(CH2)2-, -(CH2)3- O-(CH2)3-O-(CH2)3-, -(CH2)2-O-(CH2)2-O-(CH2)6-, -(CH2)6-O-(CH2)2-O- (CH2)2-, -(CH2)2-O-(CH2)2-O-(CH2)8-, -(CH2)8-O-(CH2)2-O-(CH2)2-, -(CH2)2- S-(CH2)2-, -(CH2)3-S-(CH2)3-, -(CH2)2-S-(CH2)2-S-(CH2)2-, -(CH2)3-S-(CH2)3- S-(CH2)3-, -(CH2)2-S-(CH2)2-S-(CH2)6-, -(CH2)6-S-(CH2)2-S-(CH2)2-, -(CH2)2- S-(CH2)2-S-(CH2)8-, -(CH2)8-S-(CH2)2-S-(CH2)2-, -(CH2)2-(NCH3)-(CH2)2-, - (CH2)3-(NCH3)-(CH2)3-, -(CH2)2-(NCH3)-(CH2)2-(NCH3)-(CH2)2-, -(CH2)3- (NCH3)-(CH2)3-(NCH3)-(CH2)3-, -(CH2)2-(NCH3)-(CH2)2-(NCH3)-(CH2)6-, - (CH2)6-(NCH3)-(CH2)2-(NCH3)-(CH2)2-, -(CH2)2-(NCH3)-(CH2)2-(NCH3)- (CH2)8- and-(CH2)8-(NCH3)-(CH2)2-(NCH3)-(CH2)2-,
-(CH2)-(CF2)-, -(CH2)-(CF2)-(CH2)-, -(CH2)-(CF2)-(CH2)2-, -(CH2)-(CF2)- (CH2)3-, -(CH2)-(CF2)-(CH2)4-, -(CH2)-(CF2)-(CH2)5-, -(CH2)-(CF2)-(CH2)6-, - (CH2)-(CF2)-(CH2)7-, -(CH2)-(CF2)-(CH2)8-, -(CH2)-(CF2)-(CH2)9-, -(CH2)- (CF2)-(CH2)io-, -(CH2)2-(CF2)-(CH2)-, -(CH2)3-(CF2)-(CH2)-, -(CH2)4-(CF2)- (CH2)-, -(CH2)5-(CF2)-(CH2)-, -(CH2)6-(CF2)-(CH2)-, -(CH2)7-(CF2)-(CH2)-, - (CH2)8-(CF2)-(CH2)-, -(CH2)9-(CF2)-(CH2)-, -(CH2)io-(CF2)-(CH2)-, -(CH2)2- (CF2)-(CH2)2-, -(CH2)3-(CF2)-(CH2)3-, -(CH2)4-(CF2)-(CH2)4-, -(CH2)5-(CF2)- (CH2)5-, -(CH2)2-(CF2)-(CH2)-, -(CH2)2-(CF2)-(CH2)3-, -(CH2)2-(CF2)-(CH2)4-, -(CH2)2-(CF2)-(CH2)5-, -(CH2)2-(CF2)-(CH2)6-, -(CH2)2-(CF2)-(CH2)7-, -(CH2)2- (CF2)-(CH2)8-, -(CH2)2-(CF2)-(CH2)9-, -(CH2)3-(CF2)-(CH2)-, -(CH2)3-(CF2)-
(CH2)2-, -(CH2)3-(CF2)-(CH2)4-, -(CH2)3-(CF2)-(CH2)5-, -(CH2)3-(CF2)-(CH2)6-, -(CH2)3-(CF2)-(CH2)7-, -(CH2)3-(CF2)-(CH2)8-, -(CH2)4-(CF2)-(CH2)-, -(CH2)4- (CF2)-(CH2)2-, -(CH2)4-(CF2)-(CH2)3-, -(CH2)4-(CF2)-(CH2)5-, -(CH2)4-(CF2)- (CH2)6-, -(CH2)4-(CF2)-(CH2)7-, -(CH2)5-(CF2)-(CH2)-, -(CH2)5-(CF2)-(CH2)2-, -(CH2)5-(CF2)-(CH2)3-, -(CH2)5-(CF2)-(CH2)4-, -(CH2)5-(CF2)-(CH2)6-, -(CH2)6- (CF2)-(CH2)-, -(CH2)6-(CF2)-(CH2)2-, -(CH2)6-(CF2)-(CH2)3-, -(CH2)6-(CF2)- (CH2)4-, -(CH2)6-(CF2)-(CH2)5-,
-(CH2)-(CFH)-, -(CH2)-(CFH)-(CH2)-, -(CH2)-(CFH)-(CH2)2-, -(CH2)-(CFH)- (CH2)3-, -(CH2)-(CFH)-(CH2)4-, -(CH2)-(CFH)-(CH2)5-, -(CH2)-(CFH)-(CH2)6-, -(CH2)-(CFH)-(CH2)7-, -(CH2)-(CFH)-(CH2)8-, -(CH2)-(CFH)-(CH2)9-, -(CH2)- (CFH)-(CH2)io-, -(CH2)2-(CFH)-(CH2)-, -(CH2)3-(CFH)-(CH2)-, -(CH2)4- (CFH)-(CH2)-, -(CH2)5-(CFH)-(CH2)-, -(CH2)6-(CFH)-(CH2)-, -(CH2)7-(CFH)- (CH2)-, -(CH2)8-(CFH)-(CH2)-, -(CH2)9-(CFH)-(CH2)-, -(CH2)io-(CFH)-(CH2)-, -(CH2)2-(CFH)-(CH2)2-, -(CH2)3-(CFH)-(CH2)3-, -(CH2)4-(CFH)-(CH2)4- , -(CH2)5-(CFH)-(CH2)5-, -(CH2)2-(CFH)-(CH2)-, -(CH2)2-(CFH)-(CH2)3-, - (CH2)2-(CFH)-(CH2)4-, -(CH2)2-(CFH)-(CH2)5-, -(CH2)2-(CFH)-(CH2)6-, - (CH2)2-(CFH)-(CH2)7-, -(CH2)2-(CFH)-(CH2)8-, -(CH2)2-(CFH)-(CH2)9-, - (CH2)3-(CFH)-(CH2)-, -(CH2)3-(CFH)-(CH2)2-, -(CH2)3-(CFH)-(CH2)4-, - (CH2)3-(CFH)-(CH2)5-, -(CH2)3-(CFH)-(CH2)6-, -(CH2)3-(CFH)-(CH2)7-, - (CH2)3-(CFH)-(CH2)8-, -(CH2)4-(CFH)-(CH2)-, -(CH2)4-(CFH)-(CH2)2-, - (CH2)4-(CFH)-(CH2)3-, -(CH2)4-(CFH)-(CH2)5-, -(CH2)4-(CFH)-(CH2)6-, - (CH2)4-(CFH)-(CH2)7-, -(CH2)5-(CFH)-(CH2)-, -(CH2)5-(CFH)-(CH2)2-, -
(CH2)5-(CFH)-(CH2)3-, -(CH2)5-(CFH)-(CH2)4-, -(CH2)5-(CFH)-(CH2)6-, - (CH2)6-(CFH)-(CH2)-, -(CH2)6-(CFH)-(CH2)2-, -(CH2)6-(CFH)-(CH2)3-, - (CH2)6-(CFH)-(CH2)4-, -(CH2)6-(CFH)-(CH2)5-,
-(CH2)-(CF2)2-, -(CH2)-(CF2)2-(CH2)-, -(CH2)-(CF2)2-(CH2)2-, -(CH2)-(CF2)2- (CH2)3-, -(CH2)-(CF2)2-(CH2)4-, -(CH2)-(CF2)2-(CH2)5-, -(CH2)-(CF2)2-(CH2)6- -(CH2)-(CF2)2-(CH2)7-, -(CH2)-(CF2)2-(CH2)8-, -(CH2)-(CF2)2-(CH2)9-, -(CH2)2 (CF2)2-(CH2)-, -(CH2)3-(CF2)2-(CH2)-, -(CH2)4-(CF2)2-(CH2)-, -(CH2)5-(CF2)2- (CH2)-, -(CH2)6-(CF2)2-(CH2)-, -(CH2)7-(CF2)2-(CH2)-, -(CH2)8-(CF2)2-(CH2)-, -(CH2)9-(CF2)2-(CH2)-, -(CH2)2-(CF2)2-(CH2)2-, -(CH2)3-(CF2)2-(CH2)3-, - (CH2)4-(CF2)2-(CH2)4-, -(CH2)5-(CF2)2-(CH2)5-, -(CH2)2-(CF2)2-(CH2)-,-(CH2) (CF2)2-(CH2)3-, -(CH2)2-(CF2)2-(CH2)4-, -(CH2)2-(CF2)2-(CH2)5-, -(CH2)2- (CF2)2-(CH2)6-, -(CH2)2-(CF2)2-(CH2)7-, -(CH2)2-(CF2)2-(CH2)8-, -(CH2)3- (CF2)2-(CH2)-, -(CH2)3-(CF2)2-(CH2)2-, -(CH2)3-(CF2)2-(CH2)4-, -(CH2)3- (CF2)2-(CH2)5-, -(CH2)3-(CF2)2-(CH2)6-, -(CH2)3-(CF2)2-(CH2)7-, -(CH2)4- (CF2)2-(CH2)-, -(CH2)4-(CF2)2-(CH2)2-, -(CH2)4-(CF2)2-(CH2)3-, -(CH2)4- (CF2)2-(CH2)5-, -(CH2)4-(CF2)2-(CH2)6-, -(CH2)5-(CF2)2-(CH2)-, -(CH2)5- (CF2)2-(CH2)2-, -(CH2)5-(CF2)2-(CH2)3-, -(CH2)5-(CF2)2-(CH2)4-, -(CH2)6- (CF2)2-(CH2)-, -(CH2)6-(CF2)2-(CH2)2-, -(CH2)6-(CF2)2-(CH2)3-, -(CH2)6- (CF2)2-(CH2)4-,
-(CH2)-(CFH)2-, -(CH2)-(CFH)2-(CH2)-, - (CH2)-(CFH)2-(CH2)2-, - (CH2)-
(CFH)2- (CH2)3-, -(CH2)-(CFH)2-(CH2)4-, -(CH2)-(CFH)2-(CH2)5-, -(CH2)-
(CFH)2- (CH2)6-, -(CH2)-(CFH)2-(CH2)7-, -(CH2)-(CFH)2-(CH2)8-, -(CH2)-
(CFH)2- (CH2)9-, -(CH2)2-(CFH)2-(CH2)-, -(CH2)3-(CFH)2-(CH2)-, -(CH2)4-
(CFH)2- (CH2)-, -(CH2)5-(CFH)2-(CH2)-, -(CH2)6-(CFH)2-(CH2)-, - (CH2)7-
(CFH)2- (CH2)-, -(CH2)8-(CFH)2-(CH2)-, -(CH2)9-(CFH)2-(CH2)-, - (CH2)2-
(CFH)2- (CH2)2-, -(CH2)3-(CFH)2-(CH2)3- , -(CH2)4-(CFH)2-(CH2)4 -, -(CH2)5-
(CFH)2- (CH2)5-, -(CH2)2-(CFH)2-(CH2)-, -(CH2)2-(CFH)2-(CH2)3-, -(CH2)2-
(CFH)2- (CH2)4- -(CH2)2-(CFH)2-(CH2)5- , -(CH2)2-(CFH)2-(CH2)6 -, -(CH2)2-
(CFH)2- (CH2)7- -(CH2)2-(CFH)2-(CH2)8- , -(CH2)3-(CFH)2-(CH2)- , -(CH2)3-
(CFH)2- (CH2)2- -(CH2)3-(CFH)2-(CH2)4- , -(CH2)3-(CFH)2-(CH2)5 -, -(CH2)3-
(CFH)2- (CH2)6- -(CH2)3-(CFH)2-(CH2)7- , -(CH2)4-(CFH)2-(CH2)- , -(CH2)4-
(CFH)2- (CH2)2- -(CH2)4-(CFH)2-(CH2)3- , -(CH2)4-(CFH)2-(CH2)5 -, -(CH2)4-
(CFH)2-(CH2)6-, -(CH2)5-(CFH)2-(CH2)-, -(CH2)5-(CFH)2-(CH2)2-, -(CH2)5- (CFH)2-(CH2)3-, -(CH2)5-(CFH)2-(CH2)4-, -(CH2)6-(CFH)2-(CH2)-, -(CH2)6- (CFH)2-(CH2)2-, -(CH2)6-(CFH)2-(CH2)3-, -(CH2)6-(CFH)2-(CH2)4-,
-(CH2)-(CF2)3-, -(CH2)-(CF2)3-(CH2)-, -(CH2)-(CF2)3-(CH2)2-, -(CH2)-(CF2)3- (CH2)3-, -(CH2)-(CF2)3-(CH2)4-, -(CH2)-(CF2)3-(CH2)5-, -(CH2)-(CF2)3-(CH2)6 -(CH2)-(CF2)3-(CH2)7-, -(CH2)-(CF2)3-(CH2)8-, -(CH2)2-(CF2)3-(CH2)-, -(CH2) (CF2)3-(CH2)-, -(CH2)4-(CF2)3-(CH2)-, -(CH2)5-(CF2)3-(CH2)-, -(CH2)6-(CF2)3 (CH2)-, -(CH2)7-(CF2)3-(CH2)-, -(CH2)8-(CF2)3-(CH2)-, -(CH2)2-(CF2)3-(CH2)2 -(CH2)3-(CF2)3-(CH2)3-, -(CH2)4-(CF2)3-(CH2)4-, -(CH2)2-(CF2)3-(CH2)-,- (CH2)2-(CF2)3-(CH2)3-, -(CH2)2-(CF2)3-(CH2)4-, -(CH2)2-(CF2)3-(CH2)5-, - (CH2)2-(CF2)3-(CH2)6-, -(CH2)2-(CF2)3-(CH2)7-, -(CH2)3-(CF2)3-(CH2)-, - (CH2)3-(CF2)3-(CH2)2-, -(CH2)3-(CF2)3-(CH2)4-, -(CH2)3-(CF2)3-(CH2)5-, - (CH2)3-(CF2)3-(CH2)6-, -(CH2)4-(CF2)3-(CH2)-, -(CH2)4-(CF2)3-(CH2)2-, - (CH2)4-(CF2)3-(CH2)3-, -(CH2)4-(CF2)3-(CH2)5-, -(CH2)5-(CF2)3-(CH2)-, - (CH2)5-(CF2)3-(CH2)2-, -(CH2)5-(CF2)3-(CH2)3-, -(CH2)5-(CF2)3-(CH2)4-, (CH2)6-(CF2)3-(CH2)-, -(CH2)6-(CF2)3-(CH2)2-, -(CH2)6-(CF2)3-(CH2)3-, -(CH2)-(CF2)4-, -(CH2)-(CF2)4-(CH2)-, -(CH2)-(CF2)4-(CH2)2-, -(CH2)-(CF2)4- (CH2)3-, -(CH2)-(CF2)4-(CH2)4-, -(CH2)-(CF2)4-(CH2)5-, -(CH2)-(CF2)4-(CH2)6 -(CH2)-(CF2)4-(CH2)7-, -(CH2)-(CF2)4-(CH2)8-, -(CH2)-(CF2)4-(CH2)9-, -(CH2) (CF2)4-(CH2)io-, -(CH2)2-(CF2)4-(CH2)-, -(CH2)3-(CF2)4-(CH2)-, -(CH2)4- (CF2)4-(CH2)-, -(CH2)5-(CF2)4-(CH2)-, -(CH2)6-(CF2)4-(CH2)-, -(CH2)7-(CF2)4 (CH2)-, -(CH2)2-(CF2)4-(CH2)2-, -(CH2)3-(CF2)4-(CH2)3-, -(CH2)4-(CF2)4- (CH2)4-, -(CH2)5-(CF2)4-(CH2)5-, -(CH2)2-(CF2)4-(CH2)3-, -(CH2)2-(CF2)4- (CH2)4-, -(CH2)2-(CF2)4-(CH2)5-, -(CH2)2-(CF2)4-(CH2)6-, -(CH2)3-(CF2)4- (CH2)2-, -(CH2)3-(CF2)4-(CH2)4-, -(CH2)4-(CF2)4-(CH2)2-, -(CH2)4-(CF2)4- (CH2)3-, -(CH2)5-(CF2)4-(CH2)2-, -(CH2)5-(CF2)4-(CH2)3-, -(CH2)6-(CF2)4- (CH2)2-,
-(CH2)-(CF2)5-, -(CH2)-(CF2)5-(CH2)-, -(CH2)-(CF2)5-(CH2)2-, -(CH2)-(CF2)5- (CH2)3-, -(CH2)-(CF2)5-(CH2)4-, -(CH2)-(CF2)5-(CH2)5-, -(CH2)-(CF2)5-(CH2)6 -(CH2)2-(CF2)5-(CH2)-, -(CH2)3-(CF2)5-(CH2)-, -(CH2)4-(CF2)5-(CH2)-, -(CH2) (CF2)5-(CH2)-, -(CH2)6-(CF2)5-(CH2)-, -(CH2)2-(CF2)5-(CH2)2-, -(CH2)3-(CF2) (CH2)3-, -(CH2)4-(CF2)5-(CH2)4-, -(CH2)2-(CF2)5-(CH2)3-, -(CH2)2-(CF2)5-
(CH2)4-, -(CH2)2-(CF2)5-(CH2)5-, -(CH2)2-(CF2)5-(CH2)6-, -(CH2)3-(CF2)5- (CH2)2-, -(CH2)3-(CF2)5-(CH2)4-, -(CH2)4-(CF2)5-(CH2)2-, -(CH2)4-(CF2)5- (CH2)3-, -(CH2)5-(CF2)5-(CH2)2-,
-(CH2)-(CHCF3)-, -(CH2)-(CHCF3)-(CH2)-, -(CH2)-(CHCF3)-(CH2)2-, -(CH2)- (CHCF3)-(CH2)3-, -(CH2)-(CHCF3)-(CH2)4-, -(CH2)-(CHCF3)-(CH2)5-, -(CH2)- (CHCF3)-(CH2)6-, -(CH2)-(CHCF3)-(CH2)7-, -(CH2)-(CHCF3)-(CH2)8-, -(CH2)- (CHCF3)-(CH2)9-, -(CH2)-(CHCF3)-(CH2)io-, -(CH2)2-(CHCF3)-(CH2)-, - (CH2)3-(CHCF3)-(CH2)-, -(CH2)4-(CHCF3)-(CH2)-, -(CH2)5-(CHCF3)-(CH2)-, - (CH2)6-(CHCF3)-(CH2)-, -(CH2)7-(CHCF3)-(CH2)-, -(CH2)8-(CHCF3)-(CH2)-, - (CH2)9-(CHCF3)-(CH2)-, -(CH2)io-(CHCF3)-(CH2)-, -(CH2)2-(CHCF3)-(CH2)2- -(CH2)3-(CHCF3)-(CH2)3-, -(CH2)4-(CHCF3)-(CH2)4-, -(CH2)5-(CHCF3)- (CH2)5-, -(CH2)2-(CHCF3)-(CH2)3-, -(CH2)2-(CHCF3)-(CH2)4-, -(CH2)2- (CHCF3)-(CH2)5-, -(CH2)2-(CHCF3)-(CH2)6-, -(CH2)2-(CHCF3)-(CH2)7-, - (CH2)2-(CHCF3)-(CH2)8-, -(CH2)2-(CHCF3)-(CH2)9-, -(CH2)3-(CHCF3)-(CH2)2 , -(CH2)3-(CHCF3)-(CH2)4-, -(CH2)3-(CHCF3)-(CH2)5-, -(CH2)3-(CHCF3)- (CH2)6-, -(CH2)3-(CHCF3)-(CH2)7-, -(CH2)3-(CHCF3)-(CH2)8-, -(CH2)4- (CHCF3)-(CH2)2-, -(CH2)4-(CHCF3)-(CH2)3-, -(CH2)4-(CHCF3)-(CH2)5-, - (CH2)4-(CHCF3)-(CH2)6-, -(CH2)4-(CHCF3)-(CH2)7-, -(CH2)5-(CHCF3)-(CH2)2 , -(CH2)5-(CHCF3)-(CH2)3-, -(CH2)5-(CHCF3)-(CH2)4-, -(CH2)5-(CHCF3)- (CH2)6-, -(CH2)6-(CHCF3)-(CH2)2-, -(CH2)6-(CHCF3)-(CH2)3-, -(CH2)6- (CHCF3)-(CH2)4-, -(CH2)6-(CHCF3)-(CH2)5-,
-(CH2)-(CHCF3)2-, -(CH2)-(CHCF3)2-(CH2)-, -(CH2)-(CHCF3)2-(CH2)2-, - (CH2)-(CHCF3)2-(CH2)3-, -(CH2)-(CHCF3)2-(CH2)4-, -(CH2)-(CHCF3)2-(CH2)5 , -(CH2)-(CHCF3)2-(CH2)6-, -(CH2)-(CHCF3)2-(CH2)7-, -(CH2)-(CHCF3)2- (CH2)8-, -(CH2)-(CHCF3)2-(CH2)9-, -(CH2)2-(CHCF3)2-(CH2)-, -(CH2)3- (CHCF3)2-(CH2)-, -(CH2)4-(CHCF3)2-(CH2)-, -(CH2)5-(CHCF3)2-(CH2)-, - (CH2)6-(CHCF3)2-(CH2)-, -(CH2)7-(CHCF3)2-(CH2)-, -(CH2)8-(CHCF3)2-(CH2) , -(CH2)9-(CHCF3)2-(CH2)-, -(CH2)2-(CHCF3)2-(CH2)2-, -(CH2)3-(CHCF3)2- (CH2)3-, -(CH2)4-(CHCF3)2-(CH2)4-, -(CH2)5-(CHCF3)2-(CH2)5-, -(CH2)2- (CHCF3)2-(CH2)3-, -(CH2)2-(CHCF3)2-(CH2)4-, -(CH2)2-(CHCF3)2-(CH2)5-, - (CH2)2-(CHCF3)2-(CH2)6-, -(CH2)2-(CHCF3)2-(CH2)7-, -(CH2)2-(CHCF3)2- (CH2)8-, -(CH2)3-(CHCF3)2-(CH2)2-, -(CH2)3-(CHCF3)2-(CH2)4-, -(CH2)3-
(CHCF3)2-(CH2)5-, -(CH2)3-(CHCF3)2-(CH2)6-, -(CH2)3-(CHCF3)2-(CH2)7-, - (CH2)4-(CHCF3)2-(CH2)2-, -(CH2)4-(CHCF3)2-(CH2)3-, -(CH2)4-(CHCF3)2- (CH2)5-, -(CH2)4-(CHCF3)2-(CH2)6-, -(CH2)5-(CHCF3)2-(CH2)2-, -(CH2)5- (CHCF3)2-(CH2)3-, -(CH2)5-(CHCF3)2-(CH2)4-, -(CH2)6-(CHCF3)2-(CH2)2-, - (CH2)6-(CHCF3)2-(CH2)3-, -(CH2)6-(CHCF3)2-(CH2)4-,
-(CH2)-(CHCF3)3-, -(CH2)-(CHCF3)3-(CH2)-, -(CH2)-(CHCF3)3-(CH2)2-, - (CH2)-(CHCF3)3-(CH2)3-, -(CH2)-(CHCF3)3-(CH2)4-, -(CH2)-(CHCF3)3-(CH2)5- , -(CH2)-(CHCF3)3-(CH2)6-, -(CH2)-(CHCF3)3-(CH2)7-, -(CH2)-(CHCF3)3- (CH2)8-, -(CH2)2-(CHCF3)3-(CH2)-, -(CH2)3-(CHCF3)3-(CH2)-, -(CH2)4- (CHCF3)3-(CH2)-, -(CH2)5-(CHCF3)3-(CH2)-, -(CH2)6-(CHCF3)3-(CH2)-, - (CH2)7-(CHCF3)3-(CH2)-, -(CH2)8-(CHCF3)3-(CH2)-, -(CH2)2-(CHCF3)3- (CH2)2-, -(CH2)3-(CHCF3)3-(CH2)3-, -(CH2)4-(CHCF3)3-(CH2)4-, -(CH2)2- (CHCF3)3-(CH2)3-, -(CH2)2-(CHCF3)3-(CH2)4-, -(CH2)2-(CHCF3)3-(CH2)5-, - (CH2)2-(CHCF3)3-(CH2)6-, -(CH2)2-(CHCF3)3-(CH2)7-, -(CH2)3-(CHCF3)3- (CH2)2-, -(CH2)3-(CHCF3)3-(CH2)4-, -(CH2)3-(CHCF3)3-(CH2)5-, -(CH2)3-
(CHCF3)3-(CH2)6-, -(CH2)4-(CHCF3)3-(CH2)2-, -(CH2)4-(CHCF3)3-(CH2)3-, - (CH2)4-(CHCF3)3-(CH2)5-, -(CH2)5-(CHCF3)3-(CH2)2-, -(CH2)5-(CHCF3)3- (CH2)3-, -(CH2)5-(CHCF3)3-(CH2)4-, -(CH2)6-(CHCF3)3-(CH2)2-, -(CH2)6- (CHCF3)3-(CH2)3-,
-(CH2)-(CHCF3)4-, -(CH2)-(CHCF3)4-(CH2)-, -(CH2)-(CHCF3)4-(CH2)2-, -
(CH2)-(CHCF3)4-(CH2)3-, -(CH2)-(CHCF3)4-(CH2)4-, -(CH2)-(CHCF3)4-(CH2)5- , -(CH2)-(CHCF3)4-(CH2)6-, -(CH2)-(CHCF3)4-(CH2)7-, -(CH2)-(CHCF3)4- (CH2)8-, -(CH2)-(CHCF3)4-(CH2)9-, -(CH2)-(CHCF3)4-(CH2)io-, -(CH2)2- (CHCF3)4-(CH2)-, -(CH2)3-(CHCF3)4-(CH2)-, -(CH2)4-(CHCF3)4-(CH2)-, - (CH2)5-(CHCF3)4-(CH2)-, -(CH2)6-(CHCF3)4-(CH2)-, -(CH2)7-(CHCF3)4-(CH2)- , -(CH2)2-(CHCF3)4-(CH2)2-, -(CH2)3-(CHCF3)4-(CH2)3-, -(CH2)4-(CHCF3)4- (CH2)4-, -(CH2)5-(CHCF3)4-(CH2)5-, -(CH2)2-(CHCF3)4-(CH2)3-, -(CH2)2- (CHCF3)4-(CH2)4-, -(CH2)2-(CHCF3)4-(CH2)5-, -(CH2)2-(CHCF3)4-(CH2)6-, - (CH2)3-(CHCF3)4-(CH2)2-, -(CH2)3-(CHCF3)4-(CH2)4-, -(CH2)4-(CHCF3)4- (CH2)2-, -(CH2)4-(CHCF3)4-(CH2)3-, -(CH2)5-(CHCF3)4-(CH2)2-, -(CH2)5- (CHCF3)4-(CH2)3-, -(CH2)6-(CHCF3)4-(CH2)2-,
-(CH2)-(CHCF3)5-, -(CH2)-(CHCF3)5-(CH2)-, -(CH2)-(CHCF3)5-(CH2)2-, - (CH2)-(CHCF3)5-(CH2)3-, -(CH2)-(CHCF3)5-(CH2)4-, -(CH2)-(CHCF3)5-(CH2)5- , -(CH2)-(CHCF3)5-(CH2)6-, -(CH2)2-(CHCF3)5-(CH2)-, -(CH2)3-(CHCF3)5- (CH2)-, -(CH2)4-(CHCF3)5-(CH2)-, -(CH2)5-(CHCF3)5-(CH2)-, -(CH2)6- (CHCF3)5-(CH2)-, -(CH2)2-(CHCF3)5-(CH2)2-, -(CH2)3-(CHCF3)5-(CH2)3-, - (CH2)4-(CHCF3)5-(CH2)4-, -(CH2)2-(CHCF3)5-(CH2)3-, -(CH2)2-(CHCF3)5- (CH2)4-, -(CH2)2-(CHCF3)5-(CH2)5-, -(CH2)2-(CHCF3)5-(CH2)6-, -(CH2)3- (CHCF3)5-(CH2)2-, -(CH2)3-(CHCF3)5-(CH2)4-, -(CH2)4-(CHCF3)5-(CH2)2-, - (CH2)4-(CHCF3)5-(CH2)3-, -(CH2)5-(CHCF3)5-(CH2)2-,
-(CH2)-[C(CH3)CF3]-, -(CH2)-[C(CH3)CF3]-(CH2)-, -(CH2)-[C(CH3)CF3]-
(CH2)2-, -(CH2)-[C(CH3)CF3]-(CH2)3-, -(CH2)-[C(CH3)CF3]-(CH2)4-, -(CH2)- [C(CH3)CF3]-(CH2)5-, -(CH2)-[C(CH3)CF3]-(CH2)6-, -(CH2)-[C(CH3)CF3]- (CH2)7-, -(CH2)-[C(CH3)CF3]-(CH2)8-, -(CH2)-[C(CH3)CF3]-(CH2)9-, -(CH2)- [C(CH3)CF3]-(CH2)io-, -(CH2)2-[C(CH3)CF3]-(CH2)-, -(CH2)3-[C(CH3)CF3]- (CH2)-, -(CH2)4-[C(CH3)CF3]-(CH2)-, -(CH2)5-[C(CH3)CF3]-(CH2)-, -(CH2)6- [C(CH3)CF3]-(CH2)-, -(CH2)7-[C(CH3)CF3]-(CH2)-, -(CH2)8-[C(CH3)CF3]- (CH2)-, -(CH2)9-[C(CH3)CF3]-(CH2)-, -(CH2)io-[C(CH3)CF3]-(CH2)-, -(CH2)2- [C(CH3)CF3]-(CH2)2-, -(CH2)3-[C(CH3)CF3]-(CH2)3-, -(CH2)4-[C(CH3)CF3]- (CH2)4-, -(CH2)5-[C(CH3)CF3]-(CH2)5-, -(CH2)2-[C(CH3)CF3]-(CH2)3-, -(CH2)2- [C(CH3)CF3]-(CH2)4-, -(CH2)2-[C(CH3)CF3]-(CH2)5-, -(CH2)2-[C(CH3)CF3]-
(CH2)6-, -(CH2)2-[C(CH3)CF3]-(CH2)7-, -(CH2)2-[C(CH3)CF3]-(CH2)8-, -(CH2)2- [C(CH3)CF3]-(CH2)9-, -(CH2)3-[C(CH3)CF3]-(CH2)2-, -(CH2)3-[C(CH3)CF3]- (CH2)4-, -(CH2)3-[C(CH3)CF3]-(CH2)5-, -(CH2)3-[C(CH3)CF3]-(CH2)6-, -(CH2)3- [C(CH3)CF3]-(CH2)7-, -(CH2)3-[C(CH3)CF3]-(CH2)8-, -(CH2)4-[C(CH3)CF3]- (CH2)2-, -(CH2)4-[C(CH3)CF3]-(CH2)3-, -(CH2)4-[C(CH3)CF3]-(CH2)5-, -(CH2)4- [C(CH3)CF3]-(CH2)6-, -(CH2)4-[C(CH3)CF3]-(CH2)7-, -(CH2)5-[C(CH3)CF3]- (CH2)2-, -(CH2)5-[C(CH3)CF3]-(CH2)3-, -(CH2)5-[C(CH3)CF3]-(CH2)4-, -(CH2)5- [C(CH3)CF3]-(CH2)6-, -(CH2)6-[C(CH3)CF3]-(CH2)2-, -(CH2)6-[C(CH3)CF3]- (CH2)3-, -(CH2)6-[C(CH3)CF3]-(CH2)4-, -(CH2)6-[C(CH3)CF3]-(CH2)5-,
-(CH2)-[C(CH3)CF3]2-, -(CH2)-[C(CH3)CF3]2-(CH2)-, -(CH2)-[C(CH3)CF3]2-
(CH2)2-, -(CH2)-[C(CH3)CF3]2-(CH2)3-, -(CH2)-[C(CH3)CF3]2-(CH2)4-, -(CH2)- [C(CH3)CF3]2-(CH2)5-, -(CH2)-[C(CH3)CF3]2-(CH2)6-, -(CH2)-[C(CH3)CF3]2-
(CH2)7-, -(CH2)-[C(CH3)CF3]2-(CH2)8-, -(CH2)-[C(CH3)CF3]2-(CH2)9-, -(CH2)2 [C(CH3)CF3]2-(CH2)-, -(CH2)3-[C(CH3)CF3]2-(CH2)-, -(CH2)4-[C(CH3)CF3]2- (CH2)-, -(CH2)5-[C(CH3)CF3]2-(CH2)-, -(CH2)6-[C(CH3)CF3]2-(CH2)-, -(CH2)7- [C(CH3)CF3]2-(CH2)-, -(CH2)8-[C(CH3)CF3]2-(CH2)-, -(CH2)9-[C(CH3)CF3]2- (CH2)-, -(CH2)2-[C(CH3)CF3]2-(CH2)2-, -(CH2)3-[C(CH3)CF3]2-(CH2)3-, - (CH2)4-[C(CH3)CF3]2-(CH2)4-, -(CH2)5-[C(CH3)CF3]2-(CH2)5-, -(CH2)2- [C(CH3)CF3]2-(CH2)3-, -(CH2)2-[C(CH3)CF3]2-(CH2)4-, -(CH2)2-[C(CH3)CF3]2- (CH2)5-, -(CH2)2-[C(CH3)CF3]2-(CH2)6-, -(CH2)2-[C(CH3)CF3]2-(CH2)7-, - (CH2)2-[C(CH3)CF3]2-(CH2)8-, -(CH2)3-[C(CH3)CF3]2-(CH2)2-, -(CH2)3- [C(CH3)CF3]2-(CH2)4-, -(CH2)3-[C(CH3)CF3]2-(CH2)5-, -(CH2)3-[C(CH3)CF3]2- (CH2)6-, -(CH2)3-[C(CH3)CF3]2-(CH2)7-, -(CH2)4-[C(CH3)CF3]2-(CH2)2-, - (CH2)4-[C(CH3)CF3]2-(CH2)3-, -(CH2)4-[C(CH3)CF3]2-(CH2)5-, -(CH2)4- [C(CH3)CF3]2-(CH2)6-, -(CH2)5-[C(CH3)CF3]2-(CH2)2-, -(CH2)5-[C(CH3)CF3]2- (CH2)3-, -(CH2)5-[C(CH3)CF3]2-(CH2)4-, -(CH2)6-[C(CH3)CF3]2-(CH2)2-, - (CH2)6-[C(CH3)CF3]2-(CH2)3-, -(CH2)6-[C(CH3)CF3]2-(CH2)4-,
-(CH2)-[C(CH3)CF3]3-, -(CH2)-[C(CH3)CF3]3-(CH2)-, -(CH2)-[C(CH3)CF3]3- (CH2)2-, -(CH2)-[C(CH3)CF3]3-(CH2)3-, -(CH2)-[C(CH3)CF3]3-(CH2)4-, -(CH2)- [C(CH3)CF3]3-(CH2)5-, -(CH2)-[C(CH3)CF3]3-(CH2)6-, -(CH2)-[C(CH3)CF3]3- (CH2)7-, -(CH2)-[C(CH3)CF3]3-(CH2)8-, -(CH2)2-[C(CH3)CF3]3-(CH2)-, -(CH2)3 [C(CH3)CF3]3-(CH2)-, -(CH2)4-[C(CH3)CF3]3-(CH2)-, -(CH2)5-[C(CH3)CF3]3- (CH2)-, -(CH2)6-[C(CH3)CF3]3-(CH2)-, -(CH2)7-[C(CH3)CF3]3-(CH2)-, -(CH2)8- [C(CH3)CF3]3-(CH2)-, -(CH2)2-[C(CH3)CF3]3-(CH2)2-, -(CH2)3-[C(CH3)CF3]3- (CH2)3-, -(CH2)4-[C(CH3)CF3]3-(CH2)4-, -(CH2)2-[C(CH3)CF3]3-(CH2)3-, - (CH2)2-[C(CH3)CF3]3-(CH2)4-, -(CH2)2-[C(CH3)CF3]3-(CH2)5-, -(CH2)2- [C(CH3)CF3]3-(CH2)6-, -(CH2)2-[C(CH3)CF3]3-(CH2)7-, -(CH2)3-[C(CH3)CF3]3- (CH2)2-, -(CH2)3-[C(CH3)CF3]3-(CH2)4-, -(CH2)3-[C(CH3)CF3]3-(CH2)5-, - (CH2)3-[C(CH3)CF3]3-(CH2)6-, -(CH2)4-[C(CH3)CF3]3-(CH2)2-, -(CH2)4- [C(CH3)CF3]3-(CH2)3-, -(CH2)4-[C(CH3)CF3]3-(CH2)5-, -(CH2)5-[C(CH3)CF3]3- (CH2)2-, -(CH2)5-[C(CH3)CF3]3-(CH2)3-, -(CH2)5-[C(CH3)CF3]3-(CH2)4-, - (CH2)6-[C(CH3)CF3]3-(CH2)2-, -(CH2)6-[C(CH3)CF3]3-(CH2)3-,
-(CH2)-[C(CH3)CF3]4-, -(CH2)-[C(CH3)CF3]4-(CH2)-, -(CH2)-[C(CH3)CF3]4- (CH2)2-, -(CH2)-[C(CH3)CF3]4-(CH2)3-, -(CH2)-[C(CH3)CF3]4-(CH2)4-, -(CH2)-
[C(CH3)CF3]4-(CH2)5-, -(CH2)-[C(CH3)CF3]4-(CH2)6-, -(CH2)-[C(CH3)CF3]4- (CH2)7-, -(CH2)-[C(CH3)CF3]4-(CH2)8-, -(CH2)-[C(CH3)CF3]4-(CH2)9-, -(CH2)- [C(CH3)CF3]4-(CH2)io-, -(CH2)2-[C(CH3)CF3]4-(CH2)-, -(CH2)3-[C(CH3)CF3]4- (CH2)-, -(CH2)4-[C(CH3)CF3]4-(CH2)-, -(CH2)5-[C(CH3)CF3]4-(CH2)-, -(CH2)6- [C(CH3)CF3]4-(CH2)-, -(CH2)7-[C(CH3)CF3]4-(CH2)-, -(CH2)2-[C(CH3)CF3]4- (CH2)2-, -(CH2)3-[C(CH3)CF3]4-(CH2)3-, -(CH2)4-[C(CH3)CF3]4-(CH2)4- , -(CH2)5-[C(CH3)CF3]4-(CH2)5-, -(CH2)2-[C(CH3)CF3]4-(CH2)3-, -(CH2)2- [C(CH3)CF3]4-(CH2)4-, -(CH2)2-[C(CH3)CF3]4-(CH2)5-, -(CH2)2-[C(CH3)CF3]4- (CH2)6-, -(CH2)3-[C(CH3)CF3]4-(CH2)2-, -(CH2)3-[C(CH3)CF3]4-(CH2)4-, - (CH2)4-[C(CH3)CF3]4-(CH2)2-, -(CH2)4-[C(CH3)CF3]4-(CH2)3-, -(CH2)5-
[C(CH3)CF3]4-(CH2)2-, -(CH2)5-[C(CH3)CF3]4-(CH2)3-, -(CH2)6-[C(CH3)CF3]4- (CH2)2-,
-(CH2)-[C(CH3)CF3]5-, -(CH2)-[C(CH3)CF3]5-(CH2)-, -(CH2)-[C(CH3)CF3]5- (CH2)2-, -(CH2)-[C(CH3)CF3]5-(CH2)3-, -(CH2)-[C(CH3)CF3]5-(CH2)4-, -(CH2)- [C(CH3)CF3]5-(CH2)5-, -(CH2)-[C(CH3)CF3]5-(CH2)6-, -(CH2)2-[C(CH3)CF3]5- (CH2)-, -(CH2)3-[C(CH3)CF3]5-(CH2)-, -(CH2)4-[C(CH3)CF3]5-(CH2)-, -(CH2)5- [C(CH3)CF3]5-(CH2)-, -(CH2)6-[C(CH3)CF3]5-(CH2)-, -(CH2)2-[C(CH3)CF3]5- (CH2)2-, -(CH2)3-[C(CH3)CF3]5-(CH2)3-, -(CH2)4-[C(CH3)CF3]5-(CH2)4-, - (CH2)2-[C(CH3)CF3]5-(CH2)3-, -(CH2)2-[C(CH3)CF3]5-(CH2)4-, -(CH2)2- [C(CH3)CF3]5-(CH2)5-, -(CH2)2-[C(CH3)CF3]5-(CH2)6-, -(CH2)3-[C(CH3)CF3]5- (CH2)2-, -(CH2)3-[C(CH3)CF3]5-(CH2)4-, -(CH2)4-[C(CH3)CF3]5-(CH2)2-, - (CH2)4-[C(CH3)CF3]5-(CH2)3-, -(CH2)5-[C(CH3)CF3]5-(CH2)2-,
-(CH2)-[CH(CH2CF3)]-, -(CH2)-[CH(CH2CF3)]-(CH2)-, -(CH2)-[CH(CH2CF3)]- (CH2)2-, -(CH2)-[CH(CH2CF3)] -(CH2)3-, -(CH2)-[CH(CH2CF3)]-(CH2)4-, - (CH2)-[CH(CH2CF3)]-(CH2)5-, -(CH2)-[CH(CH2CF3)]-(CH2)6-, -(CH2)-
[CH(CH2CF3)]-(CH2)7-, -(CH2)-[CH(CH2CF3)]-(CH2)8-, -(CH2)-[CH(CH2CF3)]- (CH2)9-, -(CH2)-[CH(CH2CF3)]-(CH2)io-, -(CH2)2-[CH(CH2CF3)]-(CH2)-, - (CH2)3-[CH(CH2CF3)]-(CH2)-, -(CH2)4-[CH(CH2CF3)]-(CH2)-, -(CH2)5- [CH(CH2CF3)]-(CH2)-, -(CH2)6-[CH(CH2CF3)]-(CH2)-, -(CH2)7-[CH(CH2CF3)]- (CH2)-, -(CH2)8-[CH(CH2CF3)]-(CH2)-, -(CH2)9-[CH(CH2CF3)]-(CH2)-, - (CH2)io-[CH(CH2CF3)]-(CH2)-, -(CH2)2-[CH(CH2CF3)]-(CH2)2-, -(CH2)3- [CH(CH2CF3)]-(CH2)3-, -(CH2)4-[CH(CH2CF3)]-(CH2)4-, -(CH2)5-
[CH(CH2CF3)]-( CH2)5-, -(CH2)2- [CH(CH2CF3)]-(CH2)3-, -(CH2)2-
[CH(CH2CF3)]-| ,CH2)4-, -(CH2)2- [CH(CH2CF3)]-(CH2)5-, -(CH2)2-
[CH(CH2CF3)]-| LCH2)6-, -(CH2)2- [CH(CH2CF3)]-(CH2)7-, -(CH2)2-
[CH(CH2CF3)]-| LCH2)8-, -(CH2)2- [CH(CH2CF3)]-(CH2)9-, -(CH2)3-
[CH(CH2CF3)]-| KCH2)2-, -(CH2)3- [CH(CH2CF3)]-(CH2)4-, -(CH2)3-
[CH(CH2CF3)]-| KCH2)5-, -(CH2)3- [CH(CH2CF3)]-(CH2)6-, -(CH2)3-
[CH(CH2CF3)]- [CH2)7-, -(CH2)3- [CH(CH2CF3)]-(CH2)8-, -(CH2)4-
[CH(CH2CF3)]- ;cH2)2-, -(CH2)4- [CH(CH2CF3)]-(CH2)3-, -(CH2)4-
[CH(CH2CF3)]- ;cH2)5-, -(CH2)4- [CH(CH2CF3)]-(CH2)6-, -(CH2)4-
[CH(CH2CF3)]- [CH2)7-, -(CH2)5- [CH(CH2CF3)]-(CH2)2-, -(CH2)5-
[CH(CH2CF3)1- ;CH2)3-, -(CH2)5- [CH(CH2CF3)]-(CH2)4-, -(CH2)5-
[CH(CH2CF3)]- CH2)6-, -(CH2)6- [CH(CH2CF3)]-(CH2)2-, -(CH2)6-
[CH(CH2CF3)]- (CH2)3-, -(CH2)6- [CH(CH2CF3)]-(CH2)4-, -(CH2)6-
[CH(CH2CF3)]- (CH2)5-,
-(CH2)-[CH(CH2CF3)]2- -(CH2)- [CH(CH2CF3)]2-(CH2)-, -(CH2)-
[CH(CH2CF3)]2 -(CH2)2- . -(CH2)- [CH(CH2CF3)]2-(CH2)3-, -(CH2)-
[CH(CH2CF3)]2 -(CH2)4- . -(CH2)- [CH(CH2CF3)]2-(CH2)5-, -(CH2)-
[CH(CH2CF3)]2 -(CH2)6- , -(CH2)- [CH(CH2CF3)]2-(CH2)7-, -(CH2)-
[CH(CH2CF3)]2 -(CH2)8- , -(CH2)- [CH(CH2CF3)]2-(CH2)9-, -(CH2)2
[CH(CH2CF3)]2 -(CH2)-, -(CH2)3- [CH(CH2CF3)]2-(CH2)-, -(CH2)4-
[CH(CH2CF3)]2 -(CH2)-, -(CH2)5- [CH(CH2CF3)]2-(CH2)-, -(CH2)6-
[CH(CH2CF3)]2 -(CH2)-, -(CH2)7- [CH(CH2CF3)]2-(CH2)-, -(CH2)e-
[CH(CH2CF3)]2 -(CH2)-, -(CH2)9- [CH(CH2CF3)]2-(CH2)-, -(CH2)2-
[CH(CH2CF3)]2 -(CH2)2- , -(CH2)3 -[CH(CH2CF3)]2-(CH2)3-
[CH(CH2CF3)]2 -(CH2)4- , -(CH2)5 -[CH(CH2CF3)]2-(CH2)5- ; -(CH2)
[CH(CH2CF3)]2 -(CH2)3- , -(CH2)2 -[CH(CH2CF3)]2-(CH2)4- -(CH2)
[CH(CH2CF3)]2 -(CH2)5- , -(CH2)2 -[CH(CH2CF3)]2-(CH2)6- -, -(CH2)
[CH(CH2CF3)]2 -(CH2)7- , -(CH2)2 -[CH(CH2CF3)]2-(CH2)8- -(CH2)
[CH(CH2CF3)]2 -(CH2)2- , -(CH2)3 -[CH(CH2CF3)]2-(CH2)4- -(CH2)
[CH(CH2CF3)]2 -(CH2)5- , -(CH2)3 -[CH(CH2CF3)]2-(CH2)6 -, -(CH2)
[CH(CH2CF3)]2 -(CH2)7- , -(CH2)4 -[CH(CH2CF3)]2-(CH2)2 -, -(CH2)
[CH(CH2CF3)]2 -(CH2)3- , -(CH2)4 -[CH(CH2CF3)]2-(CH2)5 -, -(CH2)
[CH(CH2CF3)]2-(CH2)6-, -(CH2)5-[CH(CH2CF3)]2-(CH2)2-, -(CH2)5 [CH(CH2CF3)]2-(CH2)3-, -(CH2)5-[CH(CH2CF3)]2-(CH2)4-, -(CH2)6 [CH(CH2CF3)]2-(CH2)2-, -(CH2)6-[CH(CH2CF3)]2-(CH2)3-) -(CH2)6 [CH(CH2CF3)]2-(CH2)4-,
-(CH2)-[CH(CH2CF3)]3-, -(CH2)-[CH(CH2CF3)]3-(CH2)-, -(CH2)- [CH(CH2CF3)]3-(CH2)2-, -(CH2)-[CH(CH2CF3)]3-(CH2)3-, -(CH2)- [CH(CH2CF3)]3-(CH2)4-, -(CH2)-[CH(CH2CF3)]3-(CH2)5-, -(CH2)- [CH(CH2CF3)]3-(CH2)6-, -(CH2)-[CH(CH2CF3)]3-(CH2)7-, -(CH2)- [CH(CH2CF3)]3-(CH2)8-, -(CH2)2-[CH(CH2CF3)]3-(CH2)-, -(CH2)3- [CH(CH2CF3)]3-(CH2)-, -(CH2)4-[CH(CH2CF3)]3-(CH2)-, -(CH2)5- [CH(CH2CF3)]3-(CH2)-, -(CH2)6-[CH(CH2CF3)]3-(CH2)-, -(CH2)7- [CH(CH2CF3)]3-(CH2)-, -(CH2)8-[CH(CH2CF3)]3-(CH2)-, -(CH2)2- [CH(CH2CF3)]3-(CH2)2-, -(CH2)3-[CH(CH2CF3)]3-(CH2)3-, -(CH2)4 [CH(CH2CF3)]3-(CH2)4-, -(CH2)2-[CH(CH2CF3)]3-(CH2)3-) -(CH2) [CH(CH2CF3)]3-(CH2)4-, -(CH2)2-[CH(CH2CF3)]3-(CH2)5-) -(CH2) [CH(CH2CF3)]3-(CH2)6-, -(CH2)2-[CH(CH2CF3)]3-(CH2)7-, -(CH2) [CH(CH2CF3)]3-(CH2)2-, -(CH2)3-[CH(CH2CF3)]3-(CH2)4-, -(CH2) [CH(CH2CF3)]3-(CH2)5-, -(CH2)3-[CH(CH2CF3)]3-(CH2)6-, -(CH2)4 [CH(CH2CF3)]3-(CH2)2-, -(CH2)4-[CH(CH2CF3)]3-(CH2)3-) -(CH2) [CH(CH2CF3)]3-(CH2)5-, -(CH2)5-[CH(CH2CF3)]3-(CH2)2-) -(CH2) [CH(CH2CF3)]3-(CH2)3-, -(CH2)5-[CH(CH2CF3)]3-(CH2)4-, -(CH2) [CH(CH2CF3)]3-(CH2)2-, -(CH2)6-[CH(CH2CF3)]3-(CH2)3-, -(CH2)-[CH(CH2CF3)]4-, -(CH2)-[CH(CH2CF3)]4-(CH2)-, -(CH2)- [CH(CH2CF3)]4-(CH2)2-, -(CH2)-[CH(CH2CF3)]4-(CH2)3-, -(CH2)- [CH(CH2CF3)]4-(CH2)4-, -(CH2)-[CH(CH2CF3)]4-(CH2)5-, -(CH2)- [CH(CH2CF3)]4-(CH2)6-, -(CH2)-[CH(CH2CF3)]4-(CH2)7-, -(CH2)- [CH(CH2CF3)]4-(CH2)8-, -(CH2)-[CH(CH2CF3)]4-(CH2)9-, -(CH2)- [CH(CH2CF3)]4-(CH2)io-, -(CH2)2-[CH(CH2CF3)]4-(CH2)-, -(CH2) [CH(CH2CF3)]4-(CH2)-, -(CH2)4-[CH(CH2CF3)]4-(CH2)-, -(CH2)5- [CH(CH2CF3)]4-(CH2)-, -(CH2)6-[CH(CH2CF3)]4-(CH2)-, -(CH2)7- [CH(CH2CF3)]4-(CH2)-, -(CH2)2-[CH(CH2CF3)]4-(CH2)2-, -(CH2)3 [CH(CH2CF3)]4-(CH2)3-, -(CH2)4-[CH(CH2CF3)]4-(CH2)4-, -(CH2)
[CH(CH2CF3)]4-(CH2)5-, -(CH2)2-[CH(CH2CF3)]4-(CH2)3-, -(CH2)2- [CH(CH2CF3)]4-(CH2)4-, -(CH2)2-[CH(CH2CF3)]4-(CH2)5-, -(CH2)2- [CH(CH2CF3)]4-(CH2)6-, -(CH2)3-[CH(CH2CF3)]4-(CH2)2-, -(CH2)3- [CH(CH2CF3)]4-(CH2)4-, -(CH2)4-[CH(CH2CF3)]4-(CH2)2-, -(CH2)4- [CH(CH2CF3)]4-(CH2)3-, -(CH2)5-[CH(CH2CF3)]4-(CH2)2-, -(CH2)5- [CH(CH2CF3)]4-(CH2)3-, -(CH2)6-[CH(CH2CF3)]4-(CH2)2-,
-(CH2)-[CH(CH2CF3)5-, -(CH2)-[CH(CH2CF3)]5-(CH2)-, -(CH2)- [CH(CH2CF3)]5-(CH2)2-, -(CH2)-[CH(CH2CF3)]5-(CH2)3-, -(CH2)- [CH(CH2CF3)]5-(CH2)4-, -(CH2)-[CH(CH2CF3)]5-(CH2)5-, -(CH2)- [CH(CH2CF3)]5-(CH2)6-, -(CH2)2-[CH(CH2CF3)]5-(CH2)-, -(CH2)3- [CH(CH2CF3)]5-(CH2)-, -(CH2)4-[CH(CH2CF3)]5-(CH2)-, -(CH2)5- [CH(CH2CF3)]5-(CH2)-, -(CH2)6-[CH(CH2CF3)]5-(CH2)-, -(CH2)2- [CH(CH2CF3)]5-(CH2)2-, -(CH2)3-[CH(CH2CF3)]5-(CH2)3-, -(CH2)4- [CH(CH2CF3)]5-(CH2)4-, -(CH2)2-[CH(CH2CF3)]5-(CH2)3-, -(CH2)2- [CH(CH2CF3)]5-(CH2)4-, -(CH2)2-[CH(CH2CF3)]5-(CH2)5-, -(CH2)2- [CH(CH2CF3)]5-(CH2)6-, -(CH2)3-[CH(CH2CF3)]5-(CH2)2-, -(CH2)3- [CH(CH2CF3)]5-(CH2)4-, -(CH2)4-[CH(CH2CF3)]5-(CH2)2-, -(CH2)4- [CH(CH2CF3)]5-(CH2)3-, -(CH2)5-[CH(CH2CF3)]5-(CH2)2-,
-(CH2)-[C(CH3)(CH2CF3)]-, -(CH2)-[C(CH3)(CH2CF3)]-(CH2)-, -(CH2)- [C(CH3)(CH2CF3)]-(CH2)2-, -(CH2)-[C(CH3)(CH2CF3)]-(CH2)3-, -(CH2)- [C(CH3)(CH2CF3)]-(CH2)4-, -(CH2)-[C(CH3)(CH2CF3)]-(CH2)5-, -(CH2)- [C(CH3)(CH2CF3)]-(CH2)6-, -(CH2)-[C(CH3)(CH2CF3)]-(CH2)7-, -(CH2)- [C(CH3)(CH2CF3)]-(CH2)8-, -(CH2)-[C(CH3)(CH2CF3)]-(CH2)9-, -(CH2)- [C(CH3)(CH2CF3)]-(CH2)10-, -(CH2)2-[C(CH3)(CH2CF3)]-(CH2)-, -(CH2) [C(CH3)(CH2CF3)]-(CH2)-, -(CH2)4-[C(CH3)(CH2CF3)]-(CH2)-, -(CH2)5- [C(CH3)(CH2CF3)]-(CH2)-, -(CH2)6-[C(CH3)(CH2CF3)]-(CH2)-, -(CH2)7- [C(CH3)(CH2CF3)]-(CH2)-, -(CH2)8-[C(CH3)(CH2CF3)]-(CH2)-, -(CH2)9- [C(CH3)(CH2CF3)]-(CH2)-, -(CH2)io-[C(CH3)(CH2CF3)]-(CH2)-, -(CH2)2 [C(CH3)(CH2CF3)]-(CH2)2-, -(CH2)3-[C(CH3)(CH2CF3)]-(CH2)3-, -(CH2) [C(CH3)(CH2CF3)]-(CH2)4-, -(CH2)5-[C(CH3)(CH2CF3)]-(CH2)5-, -(CH2) [C(CH3)(CH2CF3)]-(CH2)3-, -(CH2)2-[C(CH3)(CH2CF3)]-(CH2)4-, -(CH2) [C(CH3)(CH2CF3)]-(CH2)5-, -(CH2)2-[C(CH3)(CH2CF3)]-(CH2)6-, -(CH2)
[C(CH3) (CH2CF3) ]-(CH2)7-, -(CH2)2- [C(CH3)(CH2CF3)]-(CH2)8-, -(CH2)2-
[C(CH3) (CH2CF3) ]-(CH2)9-, -(CH2)3- [C(CH3)(CH2CF3)]-(CH2)2-, -(CH2)3-
[C(CH3) (CH2CF3) ]-(CH2)4-, -(CH2)3- [C(CH3)(CH2CF3)]-(CH2)5-, -(CH2)3-
[C(CH3) (CH2CF3) ]-(CH2)6-, -(CH2)3- [C(CH3)(CH2CF3)]-(CH2)7-, -(CH2)3-
[C(CH3) (CH2CF3) ]-(CH2)8-, -(CH2)4- [C(CH3)(CH2CF3)]-(CH2)2-, -(CH2)4-
[C(CH3) (CH2CF3) ]-(CH2)3-, -(CH2)4- [C(CH3)(CH2CF3)]-(CH2)5-, -(CH2)4-
[C(CH3) (CH2CF3) ]-(CH2)6-, -(CH2)4- [C(CH3)(CH2CF3)]-(CH2)7-, -(CH2)5-
[C(CH3) (CH2CF3) ]-(CH2)2-, -(CH2)5- [C(CH3)(CH2CF3)]-(CH2)3-, -(CH2)5-
[C(CH3) (CH2CF3) ]-(CH2)4-, -(CH2)5- [C(CH3)(CH2CF3)]-(CH2)6-, -(CH2)6-
[C(CH3) (CH2CF3) ]-(CH2)2-, -(CH2)6- [C(CH3)(CH2CF3)]-(CH2)3-, -(CH2)6-
[C(CH3) (CH2CF3) ]-(CH2)4-, -(CH2)6- [C(CH3)(CH2CF3)]-(CH2)5-,
-(CH2)-[ C(CH3)(CH2CF3)]2- -(CH2)- [C(CH3)(CH2CF3)]2-(CH2)-, -(CH2)-
[C(CH3) (CH2CF3) ]2-(CH2)2- -(CH2)- [C(CH3)(CH2CF3)]2-(CH2)3-, -(CH2)-
[C(CH3) (CH2CF3) ]2-(CH2)4- -(CH2)- [C(CH3)(CH2CF3)]2-(CH2)5-, -(CH2)-
[C(CH3) (CH2CF3) ]2-(CH2)6- -(CH2)- [C(CH3)(CH2CF3)]2-(CH2)7-, -(CH2)-
[C(CH3) (CH2CF3) ]2-(CH2)8- -(CH2)- [C(CH3)(CH2CF3)]2-(CH2)9-, -(CH2)2-
[C(CH3) (CH2CF3) ]2-(CH2)-, -(CH2)3- [C(CH3)(CH2CF3)]2-(CH2)-, -(CH2)4-
[C(CH3) (CH2CF3) ]2-(CH2)-, -(CH2)5- [C(CH3)(CH2CF3)]2-(CH2)-, -(CH2)6-
[C(CH3) (CH2CF3) ]2-(CH2)-, -(CH2)7- [C(CH3)(CH2CF3)]2-(CH2)-, -(CH2)e-
[C(CH3) (CH2CF3) ]2-(CH2)-, -(CH2)9- [C(CH3)(CH2CF3)]2-(CH2)-, -(CH2)2-
[C(CH3) (CH2CF3) ]2-(CH2)2- -(CH2)3 -[C(CH3)(CH2CF3)]2-(CH2)3- , -(CH2)4-
[C(CH3) (CH2CF3) ]2-(CH2)4- -(CH2)5 -[C(CH3)(CH2CF3)]2-(CH2)5- , -(CH2)2-
[C(CH3) (CH2CF3) ]2-(CH2)3- -(CH2)2 -[C(CH3)(CH2CF3)]2-(CH2)4- , -(CH2)2-
[C(CH3) (CH2CF3) ]2-(CH2)5- -(CH2)2 -[C(CH3)(CH2CF3)]2-(CH2)6- , -(CH2)2-
[C(CH3) (CH2CF3) ]2-(CH2)7- -(CH2)2 -[C(CH3)(CH2CF3)]2-(CH2)8- , -(CH2)3-
[C(CH3) (CH2CF3) ]2-(CH2)2- -(CH2)3 -[C(CH3)(CH2CF3)]2-(CH2)4- , -(CH2)3-
[C(CH3) (CH2CF3) ]2-(CH2)5- -(CH2)3 -[C(CH3)(CH2CF3)]2-(CH2)6- , -(CH2)3-
[C(CH3) (CH2CF3) ]2-(CH2)7- -(CH2)4 -[C(CH3)(CH2CF3)]2-(CH2)2- , -(CH2)4-
[C(CH3) (CH2CF3) ]2-(CH2)3- -(CH2)4 -[C(CH3)(CH2CF3)]2-(CH2)5- , -(CH2)4-
[C(CH3) (CH2CF3) ]2-(CH2)6- -(CH2)5 -[C(CH3)(CH2CF3)]2-(CH2)2- , -(CH2)5-
[C(CH3) (CH2CF3) ]2-(CH2)3- -(CH2)5 -[C(CH3)(CH2CF3)]2-(CH2)4- , -(CH2)6-
[C(CH3) (CH2CF3)]2-■(CH2)2-, -(CH2)6-[C(CH3)(CH2CF3)]2-(CH2)3- , -(CH2)6-
[C(CH3) (CH2CF3)]2- ■(CH2)4-,
-(CH2)-[ C(CH3)(CH2CF3)]3-, -(CH2)- [C(CH3)(CH2CF3)]3-(CH2)-, -(CH2)-
[C(CH3) (CH2CF3)]3- ■(CH2)2-, -(CH2)-[C(CH3)(CH2CF3)]3-(CH2)3-, -(CH2)-
[C(CH3) (CH2CF3)]3- ■(CH2)4-, -(CH2)-[C(CH3)(CH2CF3)]3-(CH2)5-, -(CH2)-
[C(CH3) (CH2CF3)]3- ■(CH2)6-, -(CH2)-[C(CH3)(CH2CF3)]3-(CH2)7-, -(CH2)-
[C(CH3) (CH2CF3)]3- ■(CH2)8-, -(CH2)2-[C(CH3)(CH2CF3)]3-(CH2)-, -(CH2)3-
[C(CH3) (CH2CF3)]3- ■(CH2)-, -(CH2)4-[C(CH3)(CH2CF3)]3-(CH2)-, - ■(CH2)5-
[C(CH3) (CH2CF3)]3- ■(CH2)-, -(CH2)6-[C(CH3)(CH2CF3)]3-(CH2)-, - ■(CH2)7-
[C(CH3) (CH2CF3)]3- ■(CH2)-, -(CH2)8-[C(CH3)(CH2CF3)]3-(CH2)-, - ■(CH2)2-
[C(CH3) (CH2CF3)]3- ■(CH2)2-, -(CH2)3-[C(CH3)(CH2CF3)]3-(CH2)3- , -(CH2)4-
[C(CH3) (CH2CF3)]3- ■(CH2)4-, -(CH2)2-[C(CH3)(CH2CF3)]3-(CH2)3- , -(CH2)2-
[C(CH3) (CH2CF3)]3- ■(CH2)4-, -(CH2)2-[C(CH3)(CH2CF3)]3-(CH2)5- , -(CH2)2-
[C(CH3) (CH2CF3)]3- ■(CH2)6-, -(CH2)2-[C(CH3)(CH2CF3)]3-(CH2)7- , -(CH2)3-
[C(CH3) (CH2CF3)]3- ■(CH2)2-, -(CH2)3-[C(CH3)(CH2CF3)]3-(CH2)4- , -(CH2)3-
[C(CH3) (CH2CF3)]3- ■(CH2)5-, -(CH2)3-[C(CH3)(CH2CF3)]3-(CH2)6- , -(CH2)4-
[C(CH3) (CH2CF3)]3- ■(CH2)2-, -(CH2)4-[C(CH3)(CH2CF3)]3-(CH2)3- , -(CH2)4-
[C(CH3) (CH2CF3)]3- -(CH2)5-, -(CH2)5-[C(CH3)(CH2CF3)]3-(CH2)2- , -(CH2)5-
[C(CH3) (CH2CF3)]3- ■(CH2)3-, -(CH2)5-[C(CH3)(CH2CF3)]3-(CH2)4- , -(CH2)6-
[C(CH3) (CH2CF3)]3- ■(CH2)2-, -(CH2)6-[C(CH3)(CH2CF3)]3-(CH2)3-
-(CH2)-[ C(CH3)(CH2CF3)]4-, -(CH2)-[C(CH3)(CH2CF3)]4-(CH2)-, - (CH2)-
[C(CH3) (CH2CF3)]4- ■(CH2)2-, -(CH2)-[C(CH3)(CH2CF3)]4-(CH2)3-, -(CH2)-
[C(CH3) (CH2CF3)]4- ■(CH2)4-, -(CH2)-[C(CH3)(CH2CF3)]4-(CH2)5-, -(CH2)-
[C(CH3) (CH2CF3)]4- ■(CH2)6-, -(CH2)-[C(CH3)(CH2CF3)]4-(CH2)7-, -(CH2)-
[C(CH3) (CH2CF3)]4- ■(CH2)8-, -(CH2)-[C(CH3)(CH2CF3)]4-(CH2)9-, -(CH2)-
[C(CH3) (CH2CF3)]4- ■(CH2)io- , -(CH2)2-[C(CH3)(CH2CF3)]4-(CH2)- , -(CH2)3-
[C(CH3) (CH2CF3)]4- ■(CH2)-, -(CH2)4-[C(CH3)(CH2CF3)]4-(CH2)-, - ■(CH2)5-
[C(CH3) (CH2CF3)]4- ■(CH2)-, -(CH2)6-[C(CH3)(CH2CF3)]4-(CH2)-, - ■(CH2)7-
[C(CH3) (CH2CF3)]4- ■(CH2)-, -(CH2)2-[C(CH3)(CH2CF3)]4-(CH2)2-, -(CH2)3-
[C(CH3) (CH2CF3)]4- ■(CH2)3-, -(CH2)4-[C(CH3)(CH2CF3)]4-(CH2)4- , -(CH2)5-
[C(CH3) (CH2CF3)]4- ■(CH2)5-, -(CH2)2-[C(CH3)(CH2CF3)]4-(CH2)3- , -(CH2)2-
[C(CH3) (CH2CF3)]4- ■(CH2)4-, -(CH2)2-[C(CH3)(CH2CF3)]4-(CH2)5- , -(CH2)2-
[C(CH3)(CH2CF3)]4-(CH2)6-, -(CH2)3-[C(CH3)(CH2CF3)]4-(CH2)2-, -(CH2)3- [C(CH3)(CH2CF3)]4-(CH2)4-, -(CH2)4-[C(CH3)(CH2CF3)]4-(CH2)2-, -(CH2)4- [C(CH3)(CH2CF3)]4-(CH2)3-, -(CH2)5-[C(CH3)(CH2CF3)]4-(CH2)2-, -(CH2)5- [C(CH3)(CH2CF3)]4-(CH2)3-, -(CH2)6-[C(CH3)(CH2CF3)]4-(CH2)2-,
-(CH2)-[C(CH3)(CH2CF3)]5-, -(CH2)-[C(CH3)(CH2CF3)]5-(CH2)-, -(CH2)- [C(CH3)(CH2CF3)]5-(CH2)2-, -(CH2)-[C(CH3)(CH2CF3)]5-(CH2)3-, -(CH2)- [C(CH3)(CH2CF3)]5-(CH2)4-, -(CH2)-[C(CH3)(CH2CF3)]5-(CH2)5-, -(CH2)- [C(CH3)(CH2CF3)]5-(CH2)6-, -(CH2)2-[C(CH3)(CH2CF3)]5-(CH2)-, -(CH2)3- [C(CH3)(CH2CF3)]5-(CH2)-, -(CH2)4-[C(CH3)(CH2CF3)]5-(CH2)-, -(CH2)5- [C(CH3)(CH2CF3)]5-(CH2)-, -(CH2)6-[C(CH3)(CH2CF3)]5-(CH2)-, -(CH2)2- [C(CH3)(CH2CF3)]5-(CH2)2-, -(CH2)3-[C(CH3)(CH2CF3)]5-(CH2)3-, -(CH2)4- [C(CH3)(CH2CF3)]5-(CH2)4-, -(CH2)2-[C(CH3)(CH2CF3)]5-(CH2)3-, -(CH2)2- [C(CH3)(CH2CF3)]5-(CH2)4-, -(CH2)2-[C(CH3)(CH2CF3)]5-(CH2)5-, -(CH2)2- [C(CH3)(CH2CF3)]5-(CH2)6-, -(CH2)3-[C(CH3)(CH2CF3)]5-(CH2)2-, -(CH2)3- [C(CH3)(CH2CF3)]5-(CH2)4-, -(CH2)4-[C(CH3)(CH2CF3)]5-(CH2)2-, -(CH2)4- [C(CH3)(CH2CF3)]5-(CH2)3-, -(CH2)5-[C(CH3)(CH2CF3)]5-(CH2)2-,
-(CH2)-(CF2)-O-(CF2)-O-(CF2)-(CH2)-, -(CH2)2-(CF2)-O-(CF2)-O-(CF2)- (CH2)2-, -(CH2)3-(CF2)-O-(CF2)-O-(CF2)-(CH2)3-, -(CH2)4-(CF2)-O-(CF2)-O- (CF2)-(CH2)4-, -(CH2)-(CF2)-O-(CF2)-O-(CF2)-(CH2)2-, -(CH2)-(CF2)-O-(CF2)- O-(CF2)-(CH2)3-, -(CH2)-(CF2)-O-(CF2)-O-(CF2)-(CH2)4-, -(CH2)-(CF2)-O-
(CF2)-O-(CF2)-(CH2)5-, -(CH2)-(CF2)-O-(CF2)-O-(CF2)-(CH2)6-, -(CH2)-(CF2)- O-(CF2)-O-(CF2)-(CH2)7-, -(CH2)2-(CF2)-O-(CF2)-O-(CF2)-(CH2)-, -(CH2)3- (CF2)-O-(CF2)-O-(CF2)-(CH2)-, -(CH2)4-(CF2)-O-(CF2)-O-(CF2)-(CH2)- , -(CH2)5-(CF2)-O-(CF2)-O-(CF2)-(CH2)-, -(CH2)6-(CF2)-O-(CF2)-O-(CF2)- (CH2)-, -(CH2)7-(CF2)-O-(CF2)-O-(CF2)-(CH2)-, -(CH2)2-(CF2)-O-(CF2)-O- (CF2)-(CH2)3-, -(CH2)2-(CF2)-O-(CF2)-O-(CF2)-(CH2)4-, -(CH2)2-(CF2)-O- (CF2)-O-(CF2)-(CH2)5-, -(CH2)2-(CF2)-O-(CF2)-O-(CF2)-(CH2)6-, -(CH2)3- (CF2)-O-(CF2)-O-(CF2)-(CH2)2-, -(CH2)4-(CF2)-O-(CF2)-O-(CF2)-(CH2)2- , -(CH2)5-(CF2)-O-(CF2)-O-(CF2)-(CH2)2-, -(CH2)6-(CF2)-O-(CF2)-O-(CF2)- (CH2)2-, -(CH2)3-(CF2)-O-(CF2)-O-(CF2)-(CH2)4-, -(CH2)4-(CF2)-O-(CF2)-O- (CF2)-(CH2)3-, -(CH2)3-(CF2)-O-(CF2)-O-(CF2)-(CH2)5-, -(CH2)5-(CF2)-O- (CF2)-O-(CF2)-(CH2)3-,
-(CH2)-(CF2)-0-(CF2)2-0-(CF2)-(CH2)-> -(CH2)2-(CF2)-0-(CF2)2-0-(CF2)- (CH2)2-, -(CH2)3-(CF2)-0-(CF2)2-0-(CF2)-(CH2)3-> -(CH2)4-(CF2)-O-(CF2)2-O- (CF2)-(CH2)4-, -(CH2)-(CF2)-0-(CF2)2-0-(CF2)-(CH2)2-> -(CH2)-(CF2)-O- (CF2)2-O-(CF2)-(CH2)3-, -(CH2)-(CF2)-O-(CF2)2-O-(CF2)-(CH2)4-, -(CH2)- (CF2)-O-(CF2)2-O-(CF2)-(CH2)5-, -(CH2)-(CF2)-O-(CF2)2-O-(CF2)-(CH2)6- > -(CH2)-(CF2)-0-(CF2)2-0-(CF2)-(CH2)7-> -(CH2)2-(CF2)-0-(CF2)2-0-(CF2)- (CH2)-, -(CH2)3-(CF2)-O-(CF2)2-O-(CF2)-(CH2)-, -(CH2)4-(CF2)-O-(CF2)2-O- (CF2)-(CH2)-, -(CH2)5-(CF2)-O-(CF2)2-O-(CF2)-(CH2)-, -(CH2)6-(CF2)-0- (CF2)2-O-(CF2)-(CH2)-, -(CH2)7-(CF2)-O-(CF2)2-O-(CF2)-(CH2)-, -(CH2)2- (CF2)-0-(CF2)2-0-(CF2)-(CH2)3-> -(CH2)2-(CF2)-O-(CF2)2-O-(CF2)-(CH2)4- > -(CH2)2-(CF2)-0-(CF2)2-0-(CF2)-(CH2)5-> -(CH2)2-(CF2)-O-(CF2)2-O-(CF2)- (CH2)6-, -(CH2)3-(CF2)-0-(CF2)2-0-(CF2)-(CH2)2-> -(CH2)4-(CF2)-O-(CF2)2-O- (CF2)-(CH2)2-, -(CH2)5-(CF2)-0-(CF2)2-0-(CF2)-(CH2)2-> -(CH2)6-(CF2)-0- (CF2)2-0-(CF2)-(CH2)2-> -(CH2)3-(CF2)-O-(CF2)2-O-(CF2)-(CH2)4-, -(CH2)4- (CF2)-0-(CF2)2-0-(CF2)-(CH2)3-> -(CH2)3-(CF2)-O-(CF2)2-O-(CF2)-(CH2)5- > -(CH2)5-(CF2)-0-(CF2)2-0-(CF2)-(CH2)3->
-(CH2)-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)-, -(CH2)2-(CF2)2-O-(CF2)2-O-(CF2)2-
(CH2)2-, -(CH2)3-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)3-, -(CH2)4-(CF2)2-O-(CF2)2- O-(CF2)2-(CH2)4-, -(CH2)-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)2-, -(CH2)-(CF2)2- O-(CF2)2-O-(CF2)2-(CH2)3-, -(CH2)-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)3-
, -(ΟΗ2)-(ΟΡ2)2-Ο-(ΟΡ2)2-Ο-(ΟΡ2)2-(ΟΗ2)4-, -(CH2)-(CF2)2-O-(CF2)2-O-(CF2)2-
(CH2)5-, -(CH2)-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)6-, -(CH2)-(CF2)2-O-(CF2)2- O-(CF2)2-(CH2)7-, -(CH2)2-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)-, -(CH2)3-(CF2)2- O-(CF2)2-O-(CF2)2-(CH2)-, -(CH2)4-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)- , -(CH2)5-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)-, -(CH2)6-(CF2)2-O-(CF2)2-O-
(CF2)2-(CH2)-, -(CH2)7-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)-, -(CH2)2-(CF2)2-O-
(CF2)2-O-(CF2)2-(CH2)3-, -(CH2)2-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)4-, -(CH2)2- (CF2)2-O-(CF2)2-O-(CF2)2-(CH2)5-, -(CH2)2-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)6- , -(CH2)3-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)2-, -(CH2)4-(CF2)2-O-(CF2)2-O- (CF2)2-(CH2)2-, -(CH2)5-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)2-, -(CH2)6-(CF2)2-O-
(CF2)2-O-(CF2)2-(CH2)2-, -(CH2)3-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)4-, -(CH2)4-
(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)3-, -(CH2)3-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)5- , -(CH2)5-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)3-,
-(CH2)-(CF2)-0-(CF2)-0-(CF2)-0-(CF2)-(CH2)-> -(CH2)2-(CF2)-0-(CF2)-0- (CF2)-O-(CF2)-(CH2)2-, -(CH2)3-(CF2)-O-(CF2)-O-(CF2)-O-(CF2)-(CH2)3- , -(CH2)4-(CF2)-O-(CF2)-O-(CF2)-O-(CF2)-(CH2)4-, -(CH2)-(CF2)-O-(CF2)-O- (CF2)-O-(CF2)-(CH2)2-, -(CH2)-(CF2)-0-(CF2)-0-(CF2)-0-(CF2)-(CH2)3- > -(CH2)-(CF2)-0-(CF2)-0-(CF2)-0-(CF2)-(CH2)4-> -(CH2)-(CF2)-O-(CF2)-O- (CF2)-O-(CF2)-(CH2)5-, -(CH2)-(CF2)-0-(CF2)-0-(CF2)-0-(CF2)-(CH2)6- > -(CH2)-(CF2)-0-(CF2)-0-(CF2)-0-(CF2)-(CH2)7-> -(CH2)2-(CF2)-0-(CF2)-0- (CF2)-0-(CF2)-(CH2)-> -(CH2)3-(CF2)-0-(CF2)-0-(CF2)-0-(CF2)-(CH2)-
, -(ΟΗ2)4-(ΟΡ2)-Ο-(ΟΡ2)-Ο-(ΟΡ2)-Ο-(ΟΡ2)-(ΟΗ2)-, -(CH2)5-(CF2)-0-(CF2)-0- (CF2)-O-(CF2)-(CH2)-, -(CH2)6-(CF2)-0-(CF2)-0-(CF2)-0-(CF2)-(CH2)- , -(ΟΗ2)7-(ΟΡ2)-Ο-(ΟΡ2)-Ο-(ΟΡ2)-Ο-(ΟΡ2)-(ΟΗ2)-, -(CH2)2-(CF2)-0-(CF2)-0- (CF2)-O-(CF2)-(CH2)3-, -(CH2)2-(CF2)-O-(CF2)-O-(CF2)-O-(CF2)-(CH2)4- , -(CH2)2-(CF2)-0-(CF2)-0-(CF2)-0-(CF2)-(CH2)5-> -(CH2)2-(CF2)-0-(CF2)-0- (CF2)-O-(CF2)-(CH2)6-, -(CH2)3-(CF2)-O-(CF2)-O-(CF2)-O-(CF2)-(CH2)2- > -(CH2)4-(CF2)-0-(CF2)-0-(CF2)-0-(CF2)-(CH2)2-> -(CH2)5-(CF2)-0-(CF2)-0- (CF2)-O-(CF2)-(CH2)2-, -(CH2)6-(CF2)-O-(CF2)-O-(CF2)-O-(CF2)-(CH2)2- , -(CH2)3-(CF2)-O-(CF2)-O-(CF2)-O-(CF2)-(CH2)4-, -(CH2)4-(CF2)-O-(CF2)-O- (CF2)-O-(CF2)-(CH2)3-, -(CH2)3-(CF2)-O-(CF2)-O-(CF2)-O-(CF2)-(CH2)5- > -(CH2)5-(CF2)-0-(CF2)-0-(CF2)-0-(CF2)-(CH2)3->
-(CH2)-(CF2)2-O-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)-, -(CH2)2-(CF2)2-O-(CF2)2- O-(CF2)2-O-(CF2)2-(CH2)2-, -(CH2)3-(CF2)2-O-(CF2)2-O-(CF2)2-O-(CF2)2- (CH2)3-, -(CH2)4-(CF2)2-O-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)4-, -(CH2)-(CF2)2- O-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)2-, -(CH2)-(CF2)2-O-(CF2)2-O-(CF2)2-O- (CF2)2-(CH2)3-, -(CH2)-(CF2)2-O-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)4-, -(CH2)- (CF2)2-O-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)5-, -(CH2)-(CF2)2-O-(CF2)2-O-
(CF2)2-O-(CF2)2-(CH2)6-, -(CH2)-(CF2)2-O-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)7-
, -(CH2)2-(CF2)2-O-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)-, -(CH2)3-(CF2)2-O- (CF2)2-O-(CF2)2-O-(CF2)2-(CH2)-, -(CH2)4-(CF2)2-O-(CF2)2-O-(CF2)2-O-
(CF2)2-(CH2)-, -(CH2)5-(CF2)2-O-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)-, -(CH2)6- (CF2)2-O-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)-, -(CH2)7-(CF2)2-O-(CF2)2-O-
(CF2)2-O-(CF2)2-(CH2)-, -(CH2)2-(CF2)2-O-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)3- , -(CH2)2-(CF2)2-O-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)4-, -(CH2)2-(CF2)2-O-
(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)5-, -(CH2)2-(CF2)2-O-(CF2)2-O-(CF2)2-O-
(CF2)2-(CH2)6-, -(CH2)3-(CF2)2-O-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)2-, -(CH2)4- (CF2)2-O-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)2-, -(CH2)5-(CF2)2-O-(CF2)2-O-
(CF2)2-O-(CF2)2-(CH2)2-, -(CH2)6-(CF2)2-O-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)2- , -(CH2)3-(CF2)2-O-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)4-, -(CH2)4-(CF2)2-O-
(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)3-, -(CH2)3-(CF2)2-O-(CF2)2-O-(CF2)2-O- -(CH2)5-, -(CH2)5-(CF2)2-O-(CF2)2-O-(CF2)2-O-(CF2)2-(CH2)3-,
Preferred examples for -R2- are -(CH2)6-, -(CH2)8-, -(CH2)i2-, -(CH2)3-(CF2)- (CH2)3-, -(CH2)2-(CFH)2-(CH2)2-, -(CH2)-(CF2)3-(CH2)-, -(CH2)2-(CF2)4- (CH2)2-, -(CH2)-[CH(CF3)]-(CH2)-, -(CH2)-[C(CH3)CF3]-(CH2)-, -(CH2)- [CH(CH2CF3)]-(CH2)-, -(CH2)-[C(CH3)(CH2CF3)]-(CH2)-, -(CH2)2-(CF2)-O- (CF2)-O-(CF2)-(CH2)2-, -(CH2)-(CF2)-O-(CF2)-O-(CF2)-O-(CF2)-(CH2)-,
Particularly preferred examples for -R2- are -(CH2)6-, -(CH2)8-, -(CH2)i2-, - (CH2)3-(CF2)-(CH2)3-, -(CH2)2-(CFH)2-(CH2)2- and -(CH2)2-(CF2)4-(CH2)2-.
Compounds of formula (I), (1-1 ), (I-2), (Γ), (I") and (P) with linkers -[B]- and substituents as described before or preferably described before having a polymerizable group as described before or preferably described before or below are preferred in case the substituent -F¾- within the at least one linking element Y-R2- corresponds to -(C(R)2)o- wherein R is at each occurrence independently H or F and o has a meaning as described before.
The invention therefore relates to compounds of formula (I), (1-1 ), (I-2), (Γ), (I") and (P) as described before or preferably described before wherein - R2- is at each occurrence independently -(C(R)2)o- wherein R is at each occurrence independently H or F and o has a meaning as described before.
The substituent Y-R2-R1 is particularly preferably selected from the group consisting of O-R2-R1, -R2-R1 and S-R2-R1 wherein -R2- has a meaning as described before or preferably or particularly preferably described before and wherein Ri is a polymerizable group or has a preferred meaning as described below. The substituent Y-R2-R1 is preferably O-R2-R1 and -R2- is selected from the group consisting of -(CH2)6-, -(CH2)8-, -(CH2)i2-, -(CH2)3-(CF2)-(CH2)3-, - (CH2)2-(CFH)2-(CH2)2-, -(CH2)-(CF2)3-(CH2)-> -(CH2)2-(CF2)4-(CH2)2-> -(CH2)- [CH(CF3)]-(CH2)-, -(CH2)-[C(CH3)CF3]-(CH2)-, -(CH2)-[CH(CH2CF3)]-(CH2)-, -(CH2)-[C(CH3)(CH2CF3)]-(CH2)-, -(CH2)2-(CF2)-0-(CF2)-0-(CF2)-(CH2)2-, - (CH2 -(CF2)-0-(CF2)-0-(CF2)-0-(CF2)-(CH2)-,
and wherein Ri is a polymerizable group which contains a Si atom or has a preferred meaning as described below.
The substituent Y-R2-R1 is preferably O-R2-R1 and -R2- is selected from the group consisting of -(CH2)6-, -(CH2)8-, -(CH2)i2-, -(CH2)3-(CF2)-(CH2)3-, - (CH2)2-(CFH)2-(CH2)2- and -(CH2)2-(CF2)4-(CH2)2-,
and wherein Ri is a polymerizable group which contains at least one Si atom.
Preferably, Ri is selected from the group consisting of a trialkoxysilyl group, a dialkoxyalkylsilyl group and silyl groups of formula (5), (6) and (7),
where alkyl means at each occurrence independently of each other a linear or branched alkyl group having 1 to 6 C atoms, alkoxy means at each occurrence independently of each other a linear or branched alkoxy group having 1 to 6 C atoms and the asterisk "*"denotes at each occurrence independently of each other a linkage to the linker [-R2-Y]n and/or [Y-R2-]m as described before or preferably described before.
Particularly preferably, Ri is selected from the group consisting of trialkoxysilyl or dialkoxyalkylsilyl, where alkyl means at each occurrence independently of each other a linear or branched alkyl group having 1 to 6 C atoms and alkoxy means at each occurrence independently of each other a linear or branched alkoxy group having 1 to 6 C atoms.
The preferred groups Ri are preferably combined with preferred groups of the linking element -R2- and/or the linking element Y-R2-. Combinations are excluded where two O atoms, two N atoms, one O atom and one S atom or one O atom and one N atom are directly bonded to each other as known for a skilled artisan in the field of organic chemistry.
The substituent Y-R2-R1 is therefore particularly preferably selected from the group consisting of
O-R2-R1 and -R2- is selected from the group consisting of -(CH2)6-, -(Chkje- -(CH2)i2-, -(CH2)3-(CF2)-(CH2)3-, -(CH2)2-(CFH)2-(CH2)2-, -(CH2)-(CF2)3- (CH2)-, -(CH2)2-(CF2)4-(CH2)2-, -(CH2)-[CH(CF3)]-(CH2)-, -(CH2)- [C(CH3)CF3]-(CH2)-, -(CH2)-[CH(CH2CF3)]-(CH2)-> -(CH2)- [C(CH3)(CH2CF3)]-(CH2)-, -(CH2)2-(CF2)-0-(CF2)-0-(CF2)-(CH2)2-> -(CH2)- (CF2 -0-(CF2)-0-(CF2 -0-(CF2)-(CH2)->
d ial koxyal kylsilyl , where alkyl means a linear or branched alkyl group having 1 to 6 C atoms and alkoxy means at each occurrence independently of each other a linear or branched alkoxy group having 1 to 6 C atoms.
The substituent Y-R2-R1 is therefore very particularly preferably selected from the group consisting of
O-R2-R1 and -R2- is selected from the group consisting of -(CH2)6-, -(Ch js-, -(CH2)i2-, -(CH2)3-(CF2)-(CH2)3-, -(CH2)2-(CFH)2-(CH2)2- and -(CH2)2-(CF2)4- (CH2)2-, wherein Ri is trialkoxysilyl or dialkoxyalkylsilyl, where alkyl means a linear or branched alkyl group having 1 to 6 C atoms and alkoxy means at each occurrence independently of each other a linear or branched alkoxy group having 1 to 6 C atoms.
Very particularly preferably, Ri is triethoxysilyl or diethoxymethylsilyl.
The invention therefore relates further to compounds of formula (I), (1-1 ), (I- 2), (Γ), (I") and/or (Γ) as described before or preferably described before wherein Ri is at each occurrence independently a triethoxysilyl group or a diethoxymethylsilyl group.
Examples for compounds of formula (I), (1-1 ), (I-2), (Γ), (I") and/or (Γ) are the following compounds Si-001 to Si-094:
30
10
15
20
25
30
The compounds of the present application may be synthesized by methods well known to the skilled person. Preferably, all syntheses are carried out under an inert atmosphere using dried solvents.
An exemplary reaction sequence is shown in Scheme 1 for the compound
Si-001 .
Scheme 1 :
The first type of reaction is a classic Pechmann condensation in acetic anhydride.
The second type of reaction is an ester hydrolysis.
The third type is a Mitsunobu reaction.
The fourth type is a hydrosilylation reaction with Karstedt's catalyst.
All these types of reaction and their reaction conditions are well known to a skilled person and can be easily optimized for the specific starting materials forming the compounds of formula (I). More details can be found in the experimental section.
As described before, the compounds of formula (I), (1-1 ), (I-2), (Γ), (I") and/or (Γ) as described before or preferably described before contain a polymerizable group and are predestinated as monomers for an
oligomerization or a polymerization.
The invention is therefore further directed to an oligomer or polymer comprising polymerized compounds of formula (I), (l-1 ),(l-2), (Γ), (I") and/or (Γ) as described before or preferably described before.
The term "polymer" generally means a molecule of high relative molecular mass, the structure of which essentially comprises the multiple repetition of units derived, actually or conceptually, from molecules of low relative molecular mass (PAC, 1996, 68, 2291 ). The term "polymer" includes homopolymers and co-polymers. The term "oligomer" generally means a molecule of intermediate relative molecular mass, the structure of which essentially comprises a small plurality of units derived, actually or conceptually, from molecules of lower relative molecular mass (PAC, 1996, 68, 2291 ). In a preferred sense according to the present invention a polymer means a compound having > 30 repeating units, and an oligomer means a compound with > 1 and < 30 repeating units. Above and below, in formulae showing a polymer, an oligomer, a
compound of formula (I), (1-1 ) or (I-2) or a monomeric unit formed from a compound of formula (I), (1-1 ) or (I-2), an asterisk ("*") denotes a linkage to
the adjacent repeating unit in the polymer chain or oligomer chain or to a terminal end group.
Suitable terminal end groups are known to the skilled artisan and depend on the polymerization method used.
The terms "repeating unit" and "monomeric unit" mean the constitutional repeating unit (CRU), which is the smallest constitutional unit the repetition of which constitutes a regular macronnolecule, a regular oligomer molecule, a regular block or a regular chain (PAC, 1996, 68, 2291 ).
Unless stated otherwise, the molecular weight is given as the number average molecular weight Mn or weight average molecular weight Mw, which is determined by gel permeation chromatography (GPC) against polystyrene standards in eluent solvents such as tetrahydrofuran, trichloromethane (TCM, chloroform), chlorobenzene or 1 ,2,4-trichloro- benzene. Unless stated otherwise, tetrahydrofurane is used as solvent. The degree of polymerization (n) means the number average degree of polymerization given as n = Mn/Mu, wherein Mu is the molecular weight of the single repeating unit as described in J. M. G. Cowie, Polymers:
Chemistry & Physics of Modern Materials, Blackie, Glasgow, 1991 .
The polydispersity (PDI) means the ratio of weight average molecular weight Mw, divided by the number average molecular weight Mn and is described with the letter D. The value of D is dimensionless and describes the broadness of the molecular weight distribution. The value of D can be calculated from the obtained values (Mw, Mn) from the GPC analysis.
In the polymers according to the the present invention, the total number of repeating units n is preferably > 30, very preferably > 100, most preferably > 200, and preferably up to 5000, very preferably up to 3000, most preferably up to 2000, including any combination of the aforementioned lower and upper limits of n.
The polymers of the present invention include homopolymers, statistical copolymers, random co-polymers, alternating co-polymers and block copolymers, and combinations of the aforementioned.
Throughout the description and claims of this specification, the words "comprise" and "contain" and variations of the words, for example
"comprising" and "comprises", mean "including but not limited to", and are not intended to (and do not) exclude other components
Preferably the polymerizable group Ri forms the regioregular, alternated, regiorandom, statistical, block or random homopolymer or co-polymer backbone or is part of the polymer backbone where Ri has a meaning as described or preferably described before. Preferably, such oligomer or polymer comprises a constitutional unit M° of formulae (1 -p-1 ), (1 -p-2), (1 -p-
3), (1 -p-4), (1 -p-5), (1 -p-6), (1 -p-7), (1 -p-8), (1 -p-9), (1 -p-10) and (1 -p-1 1 ),
wherein
-R2-, Y, R3, R4, R5, R6, X, Xo, -[B]-, R7 and "alkyl" have a meaning or a preferred meaning as described or preferably described before.
Combinations are excluded where two O atoms, two N atoms, an O atom and a S atom or an O atom and a N atom are directly linked to each other as known for a skilled artisan in the field of organic chemistry.
The co-polymer may be an oligomer or polymer comprising one or more polymerized compounds of formula (I), (1-1 ), (I-2), (Γ), (I") or (Γ") or a constitutional unit M° of formulae (1 -p-1 ) to (1 -p-1 1 ), which may be the same or different from one another, and one or more constitutional units M2, which may be the same or different from one another. Said one or more constitutional units M2 are chemically different from the units M°. Preferably, said one or more constitutional units M2 are derived by polymerization of one or more monomers selected from the group consisting of
trialkoxyalkenylsilane, dialkoxyalkylalkenylsilane or a silane of formula (8) and (9),
where the alkyl and alkoxy groups are at each occurrence independently of each other linear or branched having 1 to 6 C atoms and where the alkenyl group is at each occurrence independently linear having 2 to 4 C atoms.
Preferably, the alkenyl group is vinyl.
Particularly preferably, said one or more constitutional units M2 are derived by polymerization of one or more monomers selected from the group consisting of trialkoxyalkenylsilane and dialkoxyalkylalkenylsilane, where the alkyl and alkoxy groups are each independently linear or branched having 1 to 6 C atoms and where the alkenyl group is at each occurrence independently linear having 2 to 4 C atoms with inventive monomers as described before or preferably described before.
Alternatively the oligomer or polymer according to the invention is a homopolymer, i.e. an oligomer or polymer comprising one or more constitutional unit M° of formula of formulae (1 -p-1 ) to (1 -p-1 1 ), wherein all constitutional units M° are the same.
Exemplary polymeric compounds may be selected from the following formulae (P-001 ) to (P-094):
The letter n gives the degree of polymerization as explained before.
Preferably a co-polymer according to the invention as described before or preferably described before comprises the one or more constitutional units M° in a molar ratio ml and the one or more constitutional units M2 in a molar ratio m2, wherein the ratio ml : m2 is at least 0.01 and at most 100.
The oligomers or polymers according to the invention as described before or preferably described may be cross-linked depending on the monomer of formula (I) used.
The oligomers and polymers of the present invention may be made by any suitable method. It is, however, preferred that the present oligomers and polymers are made by reaction with sulfuric acid in case of the synthesis of polysiloxanes or by reaction with organo lithium compounds with
cyclodisilazanes according to compounds of formula (I) containing polymerizable groups of formulae (5) to (7) in toluene/THF at room temperature for the synthesis of polysilazanes.
The present invention is also directed to a composition comprising at least one compound of formula (I), (1-1 ), (I-2), (Γ), (I") or (I'") as described or preferably described before and/or an oligomer or polymer as described before or preferably described before.
A composition comprising at least one compound of formula (I), (1-1 ), (I-2), (Γ), (I") or (P) as described or preferably described before and an oligomer or polymer as described before is primarily used for the synthesis of block co-polymers with the condition that the oligomer or polymer has at least one reactive group left which may react with the monomers. Depending upon the intended use such composition may comprise further different components. Such further components may, for example, be selected from the group of UV absorbers.
The compositions may include or comprise, essentially consist of or consist of the said requisite or optional constituents. All compounds or components which can be used in the compositions are either known and commercially available or can by synthesized by known processes.
The UV absorber that may be used in the present composition is not particularly limited and can easily be selected from those generally known to the skilled person. Generally suitable UV absorbers are characterized by being unsaturated compounds, preferably compounds comprising one or more selected from group consisting of olefinic groups, aryl groups and heteroaryl groups; these groups may be present in any combination.
Suitable UV-absorbers for use in the present composition may, for example, be selected from those comprising a group selected from benzotriazole, benzophenone and triazine. Suitable UV-absorbers are, for example, disclosed in U.S. Pat. Nos. 5,290,892; 5,331 ,073 and 5,693,095.
The compounds of formula (I) according to the invention and their oligomers or polymers as described before or preferably described before are particularly well suited for use in optically active devices.
Hence the present invention is also directed to articles e.g. blanks which may be transformed into optically active devices comprising at least one compound of formula (I) as described before or preferably described before or at least one oligomer or polymer as described before or preferably described before.
Preferred articles are blanks which may be transformed into optically active devices or the optically active devices as such. Preferred optically active devices are ophthalmic devices. Examples of such ophthalmic devices include lenses, keratoprostheses, and cornea inlays or rings. More preferably, said article is a blank which may be transformed into an eye- implant or the eye-implant as such. More preferably, said eye-implant is a lens. Most preferably, such article is a blank which may be transformed into an intraocular lens or the intraocular lens as such, which may, for example,
be a posterior chamber intraocular lens or an anterior chamber intraocular lens.
A blank of this invention may be produced as a step in the manufacturing process used to create an intraocular lens. For example, without limitation, a manufacturing process may include the steps of polymer synthesis, polymer sheet casting, blank cutting, optic lathe cutting, optic milling, haptic milling or attachment, polishing, solvent extraction, sterilization and packaging.
The present articles according to the invention as described before or preferably described before may be formed by a process comprising the steps of
- providing a composition comprising at least one compound of formula (I) as described herein or preferably described herein and/or an oligomer or polymer as described herein or preferably described herein; and
- subsequently forming the article of said composition.
Intraocular lenses in accordance with the present invention are believed to show particularly advantageous properties in that they are flexible enough so as to be rolled or folded and consequently requiring a much smaller incision for them to be inserted into the eye. It is believed that this will allow for improved healing of the eye, particularly in respect to the time for the eye to heal.
The type of intraocular lens is not limited in any way. It may, for example, comprise one or more optic and one or more haptic components, wherein the one or more optic components serve as lens and the one or more haptic components are attached to the one or more optic components and hold the one or more optic components in place in the eye. The present intraocular lens may be of a one-piece design or of multi-piece design, depending on whether the one or more optic components and the one or
more haptic components are formed from a single piece of material (one- piece design) or are made separately and then combined (multi-piece design). The present intraocular lens is also designed in such a way that it allows to be, for example, rolled up or folded small enough so that it fits through an incision in the eye, said incision being as small as possible, for example, at most 3 mm in length.
Additionally, intraocular lenses in accordance with the present invention allow for the non-invasive adjustment of the optical properties, particularly the refractive power, after implantation of the lens into the eye, thus reducing the need for post-surgery vision aids or reducing or totally avoiding follow-up surgery.
In order to change the optical properties and particularly the refractive power of the intraocular lens it is exposed to irradiation having a
wavelength of at least 200 nm and of at most 1500 nm. Hence, the present invention is also directed to a process of changing the optical properties of an article as defined or preferably defined herein, said process comprising the steps of
- providing an article as defined herein; and
- subsequently exposing said article to irradiation having a wavelength of at least 200 nm and at most 1500 nm.
Preferably, said irradiation has a wavelength of at least 250 nm or 300 nm, more preferably of at least 350 nm, even more preferably of at least 400 nm, still even more preferably of at least 450 nm, and most preferably of at least 500 nm. Preferably, said irradiation has a wavelength of at most 1400 nm or 1300 nm or 1200 nm or 1 100 nm or 1000 nm, more preferably of at most 950 nm or 900 nm, even more preferably of at most 850 nm, still even more preferably of at most 800 nm and most preferably of at most 750 nm.
Examples
The following examples are intended to show the advantages of the present compounds in a non-limiting way.
Unless indicated otherwise, all syntheses can be or are carried out under an inert atmosphere using dried (i.e. water-free) solvents. Solvents and reagents are purchased or can be purchased from commercial suppliers.
DCM is used to denote dichloromethane. DMF is used to denote
dimethylformamide. EE is used to denote ethyl acetate. THF is used to denote tetrahydrofuran.
Co-polymer-properties can be investigated on blanks, prepared by bulk polymerization of the monomers. Co-monomers, cross-linkers and initiators therefore can be purchased from commercial sources. All chemicals are of highest purity available and can be used as received.
Synthesis of precursor materials:
General remarks & general synthetic procedures (GSP 1) for the synthesis of acetic acid 3-phenyl-coumarin-7-yl ester derivative:
30 g (0.213 mmol) 2,4-Dihydroxy-benzaldehyde and 29.273 g (0213 mmol) phenyl-acetic acid are dissolved in 67.47 ml acetic anhydride and 65.485 ml pyridine. The batch is stirred at 135 °C for 72 h and is then cooled to room temperature. The solid which has precipitated out is filtered off with suction and rinsed neutral with water. The residue is dried at 40 °C in vacuo. The yield of 2-oxo-3-phenyl-2/-/-chromen-7-yl acetate is 59.7 g (0.18 mmol) (87% of theory).
Analogously, other derivatives are prepared in the same manner: R1 means reactant 1 , R2 means reactant 2, [P] means product
1H NMR (500 MHz, CDCI3) δ 7.77 (d, 2H, J = 2.1 Hz), 7.63 (s, 1 H), 7.60 (dd, 1 H, J = 8.2 Hz, J = 2.2 Hz), 7.53 (d, 1 H, J = 8.4 Hz), 7.36 (d, 1 H, J = 8.2 Hz), 7.19 (d, 1 H, J = 2.1 Hz), 7.10 (dd, 1 H, J = 8.5 Hz, J = 2.2 Hz), 2.36 (s, 3H).
1H NMR (500 MHz, CDCIs) δ 8.21 (s, 1 H), 7.84 (d, 1 H, J = 8.5 Hz), 7.79- 7.72 (m, 2H), 7.58 (d, 1 H, J = 8.7 Hz), 7.37 (d, 1 H, J = 2.1 Hz), 7.22 (dd, 1 H, J = 8.4 Hz, J = 2.2 Hz), 2.33 (s, 3H).
1H NMR (500 MHz, CDCIs) δ 7.74 (s, 1 H), 7.54 (d, 1 H, J = 8.5 Hz), 7.51 (dd, 1 H, J = 7.8 Hz, J = 1 .7 Hz), 7.49-7.44 (m, 1 H), 7.40-7.35 (m, 3H), 7.18
(d, 1 H, J = 2.1 Hz), 7.38 (d, J = 2.1 Hz), 7.09 (dd, J = 8.4 Hz, J = 2.2 Hz), 2.36 (s, 3H).
1H NMR (500 MHz, CDCI3) δ 8.31 (m, 2H), 7.47 (dd, 1 H, J = 8.2 Hz, J = 1 .8 Hz), 7.43 (d, 1 H, J = 8.3 Hz), 7.29 (d, 1 H, J = 8.2 Hz), 6.89 (d, 2H, J = 8.4 Hz), 3.90 (s, 3H).
Example 2:
General remarks & general synthetic procedures (GSP 2) for the deprotection of the acetate derivative to the phenol derivative:
7.0 mmol acetic acid 3-phenyl-coumarin-7-yl ester are suspended in a mixture of 14 ml ethanol and 10 ml sulfuric acid (20%, aq.) and refluxed for 2 h. The batch is then cooled to room temperature, and the precipitated solid is filtered off with suction and rinsed neutral with water. The yield is 6.8 mmol, 97% of theory.
1H NMR (500 MHz, DMSO-d6) δ 10.59 (s, 1 H), 8.16 (s, 1 H), 7.70 (dd, 2H, J = 7.3 Hz, J = 1 .7 Hz), 7.61 (d, 1 H, J = 8.5 Hz), 7.45 (t, 2H, J = 7.5 Hz), 7.39 (t, 1 H, J = 7.3 Hz), 6.83 (dd, 1 H, J = 8.5 Hz, J = 2.2 Hz), 6.77 (d, 1 H, J = 2.2 Hz).
Analogously, other 7-hydroxy-3-phenyl-coumarin derivatives are prepared in the same manner:
1H NMR (500 MHz, DMSO-d6) δ 10.68 (s, 1 H), 8.04 (s, 1 H), 7.61 (d, J = 8.5 Hz, 1 H), 7.57 (td, J = 7.4 Hz, 1 .7 Hz, 1 H), 7.49 (dd, J = 7.2 , 1 .3 Hz, 1 H), 7.46 (d, J = 7.6 Hz, 1 H), 6.85 (dd, J = 8.5 Hz, 2.3 Hz, 1 H), 6.80 (d, J = 2.1 Hz, 1 H).
Example 3:
General remarks & general synthetic procedures (GSP 3) for the Suzuki coupling of halogenated 2-oxo-3-phenyl-2H-chromen-7-yl acetate derivatives:
3.0 g (8.4 mmol) of acetic acid 3-(4-bromophenyl)-coumarin-7-yl ester, 0.65 g (8.8 mmol) of ethylboronic acid and 3.7 g (17.5 mmol) of tri- potassium phosphate trihydrate are dissolved in 80 ml of toluene and degassed. 171 mg (0.4 mmol) of 2-dicyclohexylphoshino-2',6'-dimethoxy- 1 ,1 '-biphenyl [S-Phos] and 47 mg (0.2 mmol) of palladium(ll) acetate are added. The reaction mixture is subsequently stirred at 1 10 °C for 24 h under a protective-gas atmosphere. The cooled solution is diluted with ethyl acetate and washed with water, dried and evaporated. The product is purified by column chromatography on silica gel (heptane/ethyl acetate). Yield: 2.12 g (6.88 mmol), 82% of theory.
Under the basic conditions, deprotection of the acetate group to the corresponding phenol is observed during several Suzuki coupling reactions. To complete the deprotection step, the crude organic phase after workup is refluxed with a 1 :2 mixture sulfuric acid (~20%):ethanol until completion.
Then column chromatography of the obtained residue, as described above, is done.
1H NMR (500 MHz, DMSO-d6) δ 8.23 (s, 1 H), 7.81 (d, 1 H, J = 8.4 Hz), 7.64 (d, 2H, J = 8.2 Hz), 7.34-7.25 (m, 3H), 7.18 (dd, 1 H, J = 8.4 Hz, J = 2.2 Hz), 7.20 (dd, 1 H, J = 8.4 Hz, J = 2.1 Hz), 2.62 (t, 2H, J = 7.6 Hz), 2.32 (s, 3H), 2.72 (q, 2H), 1 .18 (t, 3H, J = 7.2 Hz).
Analogously, other Suzuki derivatives are prepared in the same manner: R1 means reactant 1 , R2 means reactant 2, [P] means product
1H NMR (500 MHz, CDCI3) δ 7.69 (d, 1 H, J = 9.9 Hz), 7.40 (d, 2H, J = 8.0 Hz), 7.18-7.15 (m, 2H), 6.96 (d, 1 H, J = 2.2 Hz), 6.83 (dd, 1 H, J = 8.5 Hz, J = 2.3 Hz), 5.98 (d, 1 H, J = 9.2 Hz), 2.71 -2.61 (m, 2H), 1 .69-1 .60 (m, 2H), 1 .37-1 .34 (m, 4H), 0.91 (t, 3H, J = 6.9 Hz).
Example 4:
General remarks & general synthetic procedures (GSP 4) for the reaction of the corresponding (fluorinated) monoalcohol with 7-hydroxy-3-phenyl-2H-chromen-2-one derivatives (Mitsunobu alkylation type reaction):
To an ice-cooled solution of 7-hydroxy-3-phenyl-2H-chromen-2-one (9.02 g, 36.94 mmol), 5-hexen-1 -ol (4.24ml, 36.94 mmol, 1 .0 equiv.), and
triphenylphosphine (9.787 g, 1 .00 equiv.) in 100ml THF, diisopropyl azodicarboxylate (7.42ml, 1 .00 equiv.) is added dropwise. After stirring at room temperature overnight, the reaction mixture is evaporated. The crude product is purified by column chromatography (cyclohexane / DCM).
9.045 g (28.23 mmol, 76% of theory) of 7-Hex-5-enyloxy-3-phenyl-2H- chromen-2-on is isolated.
Analogously, other derivatives are prepared in the same manner: R1 means reactant 1 , R2 means reactant 2, [P] means product
J = 10.2 Hz, J = 6.7 Hz), 5.06 (dd, 1 H, J = 17.2 Hz, J = 1 .8 Hz), 5.02-4.97 (m, 1 H), 4.04 (t, 2H, J = 6.5 Hz), 2.15 (q, 2H, J = 7.2 Hz), 1 .89-1 .81 (m, 2H), 1 .64-1 .55 (m, 2H). 7-(hex-5-en-1 -yloxy)-3-(4-pentyl-2-(trifluoromethyl)phenyl)-2H- chromen-2-one:
1 H NMR (500 MHz, DMSO-de) δ 7.96 (s, 1 H), 7.68 - 7.64 (m, 2H), 7.58 (d, J = 8.0 Hz, 1 H), 7.44 (d, J = 7.9 Hz, 1 H), 7.07 (d, J = 2.3 Hz, 1 H), 7.00 (dd, J = 8.6, 2.4 Hz, 1 H), 5.85 (ddt, J = 16.9, 10.2, 6.6 Hz, 1 H), 5.09 - 4.96 (m, 2H), 4.12 (t, J = 6.5 Hz, 2H), 2.76 - 2.70 (m, 2H), 2.12 (q, J = 7.2 Hz, 2H), 1 .81 - 1 .74 (m, 2H), 1 .64 (p, J = 7.5 Hz, 2H), 1 .54 (p, J = 7.6 Hz, 2H), 1 .37 - 1 .28 (m, 4H), 0.89 (t, J = 7.0 Hz, 3H).
Example 5:
General remarks & general synthetic procedures (GSP 5) for the hydrosilylation of the corresponding alkene with the Karstedt catalyst:
7-Hex-5-enyloxy-3-phenyl-2H-chromen-2-one (1 .09 g, 3.4 mmol) is dissolved in 10 ml dry DCM. The solution is saturated with an syringe in the DCM solution. Then 167 μΙ (16.7 μιτιοΙ, 0.005 equiv.) of a solution of platinum-divinyltetramethyldisiloxane complex (0.1 mol/l, in
poly(dimethylsiloxane) vinyl terminated) is added. Finally,
methyldiethoxysilane (1 .7 ml, 10.21 mmol, 3.0 equivs.) is added. The solution is stirred at room temperature until completion of the starting
material, observed by TLC analysis. The crude reaction mixture is concentrated in vacuo and purified via column chromatography using cyclohexane / ethyl acetate as eluent. 0.815 g of 7-[6-(Diethoxy-methyl- silanyl)-hexyloxy]-3-phenyl-2/-/-chromen-2-on is isolated (53% of theory).
Analogously, other derivatives are prepared in the same manner:
R1 means reactant 1 , R2 means reactant 2, [P] means product
1H NMR (500 MHz, acetone-de) δ δ 8.07 (s, 1 H), 7.81 -7.70 (m, 2H), 7.66 (d, 1 H, J = 8.6 Hz), 7.44 (t, 2H, J = 7.3 Hz), 7.38 (t, 1 H, J = 7.3 Hz), 6.96 (dd, 1 H, J = 8.5 Hz, J = 2.4 Hz), 6.93 (d, 2H, J = 2.2 Hz), 4.16 (t, 2H,
J = 6.4 Hz), 3.84-3.75 (m, 6H), 1 .83 (dt, 2H, J = 8.8 Hz, J = 6.4 Hz), 1 .54- 1 .45 (m, 6H), 1 .23-1 .12 (m, 8H), 0.64-0.61 (m, 2H).
7-((6-(diethoxy(methyl)silyl)hexyl)oxy)-3-(4-pentyl-2- (trifluoromethyl)phenyl)-2H-chromen-2-one:
1 H NMR (500 MHz, Chloroform-d) δ 7.56 (d, J = 5.1 Hz, 2H), 7.39 (dd, J = 12.1 , 8.9 Hz, 2H), 7.31 (d, J = 7.8 Hz, 1 H), 6.86 (d, J = 7.3 Hz, 2H), 4.03 (t, J = 6.5 Hz, 2H), 3.77 (q, J = 7.0 Hz, 4H), 2.72 - 2.67 (m, 2H), 1 .82 (p, J = 6.6 Hz, 2H), 1 .66 (p, J = 7.5 Hz, 2H), 1 .52 - 1 .45 (m, 2H), 1 .45 - 1 .40 (m, 4H), 1 .40 - 1 .33 (m, 4H), 1 .22 (t, J = 7.0 Hz, 6H), 0.96 - 0.88 (m, 3H), 0.64 (t, J = 7.9 Hz, 2H), 0.12 (s, 3H).
3-(4-pentyl-2-(trifluoromethyl)phenyl)-7-((6-(triethoxysilyl)hexyl)oxy)- 2H-chromen-2-one:
1 H NMR (500 MHz, CDCIs) δ 7.56 (d, J = 5.2 Hz, 2H), 7.39 (dd, J = 1 1 .9, 8.6 Hz, 2H), 7.31 (d, J = 7.8 Hz, 1 H), 6.86 (d, J = 7.3 Hz, 2H), 4.03 (t, J = 6.5 Hz, 2H), 3.82 (q, J = 7.0 Hz, 6H), 2.71 - 2.65 (m, 2H), 1 .82 (p, J = 6.8 Hz, 2H),
1 .66 (p, J = 7.5 Hz, 2H), 1 .51 - 1 .40 (m, 6H), 1 .39 - 1 .31 (m, 4H), 1 .23 (t, J = 6.9 Hz, 9H), 0.92 (t, J = 6.9 Hz, 3H), 0.69 - 0.62 (m, 2H).
Example 6:
General remarks & general synthetic procedures (GSP 6) for the solvent polymerization of the monomers:
To 7-((6-(diethoxy(methyl)silyl)hexyl)oxy)-3-phenyl-2/-/-chromen-2-one (0.15 g, 0.33 mmol, 1 .0 equiv.) concentrated sulfuric aceid (1 μΙ, cat.) is added. The reaction mixture is stirred for 72 h at 60 °C. The product is precipitated in methanol and is finally dried in vacuo at 60 °C for at minimum 5 days.
Examples of polymers within this invention are given in the following table:
Examples directed to the properties of the compounds
Example 7 - photoinduced refractive index change and glass
transition temperature
The phase transition temperatures are determined with a TA Instruments Q2000 differential scanning calorimeter during heating in the second heating run with 20 K/min from -100 °C to 200 °C in a hermetic aluminium pans.
Irradiations of the blanks are performed with a Coherent Avia 355-7000 UV- Laser.
Common photoactive polymers that undergo refractive index change upon irradiation with UV-light exhibit glass transition temperatures as low as 34°C.
Polymer films for refractive index measurements are prepared by spin coating or drop casting from 1 -8 wt% solutions of the polymers in
chloroform onto silicon wafers or quartz plates. For production of bulk polymer blanks, the monomers are melted under vacuum. Appropriate amounts of a radical initiator and cross-linker are mixed in and quickly filled into a heated polymerization chamber. Cross-linked polymer plates are obtained.
Refractive index change is induced by irradiation at 340 - 365 nm. The refractive indices (n) of the polymer films and blanks at 590 nm are measured on Schmidt+Haensch AR12 before and after irradiation. The following table shows the refractive indices before and after irradiation as well as the change in refractive index (max. Δη).
Expected values for the cited polymers are given in the following table:
Values for the cited polymer P-005 is given in the following table:
Claims
Patent claims 1. Compounds of formula (I)
wherein
X is O, S or NRo,
Xo is O or S,
Y is O, S or a bond,
n is 0 or 1 ,
m is 0 or 1 ,
n+m is 1 or 2,
-[B]- is selected from the group consisting of formula (1 ) to formula (4),
Xi, X2, X3, X4 are each independently of each other CR' or N, X5 is each independently O, S, C=O or NRo,
Χ6, X7 are each independently CR' or N,
R is at each occurrence independently selected from the group consisting of H, F, a linear or branched alkyl group having 1 to 4 C atoms or a linear or branched partially or fully fluorinated alkyl group having 1 to 4 C atoms,
R' is at each occurrence independently selected from the group consisting of H, F, a linear or branched, non- halogenated, partially or completely halogenated alkyl group having 1 to 20 C atoms, a linear or branched hydroxyalkyl group having 1 to 20 C atoms, a non- halogenated, partially or completely halogenated cycloalkyl group having 3 to 6 C atoms, a linear or branched, non-halogenated, partially or completely halogenated alkoxy group having 1 to 20 C atoms, a linear or branched, non-halogenated, partially or completely halogenated thioalkyl group having 1 to 20 C atoms,
Ro is at each occurrence independently selected from the group consisting of a linear or branched alkyl group having 1 to 10 C atoms or a cycloalkyl group having 3 to
6 C atoms,
Ri is a polymerizable group containing at least one Si atom,
-R2- is -(C(R)2)o-,
-(C(R)2)p-X8-(C(R)2)q-(X9)s-(C(R)2)^(Xio)t-(C(R)2)u- or a cycloalkylene group having 5 or 6 C atoms which can be substituted with at least one R which is different from
H,
o is selected from the group consisting of 1 to 20,
X8, X9, X10 are at each occurrence independently O, S or NRo, s, t is O or l ,
p, q are at each occurrence independently selected from the group consisting of 1 to 10,
r, u are at each occurrence independently selected from the group consisting of 0 to 10, wherein the overall number of atoms for -(C(R)2)p-X8-(C(R)2)q-(X9)s-(C(R)2)^(Xio)t- (C(R)2)u- is up to 20 atoms,
R3, R4, R5, R6 are at each occurrence independently R',
R7 is R' in case m is 0 and
R7 is Ri in case m is 1 .
2. Compounds according to claim 1 wherein -[B]- corresponds to formula (1 ) or formula (2).
3. Compounds according to claim 1 or 2 wherein Xi, X3 and X4 in formulae (1 ) or (2) are CR' and R' has at each occurrence independently a meaning as indicated in claim 1 .
4. Compounds according to one or more of claims 1 to 3 wherein X2 is CR' and R' has a meaning as indicated in claim 1 .
5. Compounds according to one or more of claims 1 to 4 wherein at least one R' within Xi, X2, X3, X4, ΧΘ or X7 in formulae (1 ) to (4) is not H.
6. Compounds according to one or more of claims 1 to 5 wherein n is 1 and m is 0 said compounds being of formula (Γ)
wherein Ri, -R2-, Y, R3, R4, R5, R6, X, Xo, -[B]- and R7 have a meaning as indicated in one of claims 1 to 5.
7. Compounds according to one or more of claims 1 to 5 wherein n is 0 and m is 1 s id compounds being of formula (I")
wherein Ri, -R2-, Y, R3, R4, R5, R6, X, Xo, -[B]- and R7 have a meaning as indicated in one of claims 1 to 5.
8. Compounds according to one or more of claims 1 to 5 wherein n is 1 and m is 1 said compounds being of formula (Γ")
wherein Ri, -R2-, Y, R3, R4, R5, R6, X, Xo, -[B]- and R7 have a meaning as indicated in one of claims 1 to 5.
9. Compounds according to one or more of claims 1 to 8 wherein -R2- is at each occurrence independently -(C(R)2)o- wherein R is at each occurrence independently H or F and o has a meaning as indicated in claim 1 .
10. Compounds according to one or more of claims 1 to 9 wherein Ri is at each occurrence independently a diethoxymethylsilyl or triethoxysilyl radical.
1 1 . Oligomer or polymer comprising polymerized compounds of formula (I) as described in one or more of claims 1 to 10.
12. Composition comprising at least one compound of formula (I) according to one or more of claims 1 to 10 and/or an oligomer or polymer according to claim 1 1 .
13. Article comprising at least one polymerized compound of formula (I) according to one or more of claims 1 to 10 or at least one oligomer or polymer of claim 1 1 .
14. Article according to claim 13 wherein said article is a blank which may be transformed into an eye implant or an eye implant, preferably an intraocular lens.
15. Process of forming an article of claim 13 or 14, said process comprising the steps of
- providing a composition comprising at least one compound of
formula (I) according to one or more of claims 1 to 10 and/or an oligomer or polymer according to claim 1 1 ;
- subsequently forming the article of said composition.
16. Process of changing the optical properties of an article according to claim 13 or 14, said process comprising the steps of
- providing an article according to claim 13 or 14, and
- subsequently exposing said article to irradiation having a wavelength of at least 200 nm and at most 1500 nm.
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|---|---|---|---|
| ES18706232T ES2882714T3 (en) | 2017-02-15 | 2018-02-14 | Compounds containing Si atoms for optically active devices |
| US16/485,886 US11040990B2 (en) | 2017-02-15 | 2018-02-14 | Compounds containing Si atoms for optically active devices |
| EP18706232.8A EP3583100B1 (en) | 2017-02-15 | 2018-02-14 | Compounds containing si atoms for optically active devices |
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| EP17156331.5 | 2017-02-15 | ||
| EP17156331.5A EP3363792A1 (en) | 2017-02-15 | 2017-02-15 | Compounds containing si atoms for optically active devices |
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| US (1) | US11040990B2 (en) |
| EP (2) | EP3363792A1 (en) |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020212543A1 (en) | 2019-04-18 | 2020-10-22 | Merck Patent Gmbh | Compounds for optically active devices |
| WO2020216928A1 (en) | 2019-04-26 | 2020-10-29 | Merck Patent Gmbh | System and method |
| WO2021233800A1 (en) | 2020-05-20 | 2021-11-25 | Merck Patent Gmbh | Azacoumarin and azathiocoumarin derivatives for use in optically active devices |
| WO2022012798A1 (en) | 2020-07-15 | 2022-01-20 | Merck Patent Gmbh | Optically active devices |
| EP4015512A1 (en) | 2020-12-16 | 2022-06-22 | AMO Ireland | Optically active devices |
| EP4036085A1 (en) | 2021-01-27 | 2022-08-03 | AMO Ireland | Compounds for optically active ophthalmic devices |
| US11702396B2 (en) | 2017-02-15 | 2023-07-18 | Johnson & Johnson Surgical Vision, Inc. | Hydrophobic compounds for optically active devices |
| US11753387B2 (en) | 2017-02-15 | 2023-09-12 | Johnson & Johnson Surgical Vision, Inc. | Compounds for optically active devices |
| US11958819B2 (en) | 2015-08-21 | 2024-04-16 | Johnson & Johnson Surgical Vision, Inc. | Compounds for optically active devices |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5290892A (en) | 1990-11-07 | 1994-03-01 | Nestle S.A. | Flexible intraocular lenses made from high refractive index polymers |
| US5331073A (en) | 1992-11-09 | 1994-07-19 | Allergan, Inc. | Polymeric compositions and intraocular lenses made from same |
| US5693095A (en) | 1995-06-07 | 1997-12-02 | Alcon Laboratories, Inc. | High refractive index ophthalmic lens materials |
| WO2006078834A1 (en) | 2005-01-21 | 2006-07-27 | Janssen Pharmaceutica N.V. | Novel heterocyclic benzo[c]chromene derivatives useful as modulators of the estrogen receptors |
| WO2007033831A1 (en) | 2005-09-23 | 2007-03-29 | Schmidt Intraocularlinsen Gmbh | Intraocular lens |
| WO2009074520A2 (en) | 2007-12-11 | 2009-06-18 | *Acri.Tec Gmbh | Copolymer and ophthalmological composition |
| WO2009074521A1 (en) | 2007-12-11 | 2009-06-18 | *Acri.Tec Gmbh | Ophthalmologic composition and use thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3133065A1 (en) * | 2015-08-21 | 2017-02-22 | Merck Patent GmbH | Compounds for optically active devices |
| EP3133066A1 (en) * | 2015-08-21 | 2017-02-22 | Merck Patent GmbH | Hydrophilic compounds for optically active devices |
| EP3363793A1 (en) * | 2017-02-15 | 2018-08-22 | Merck Patent GmbH | Hydrophobic compounds for optically active devices |
| EP3502147A1 (en) * | 2017-12-22 | 2019-06-26 | Merck Patent GmbH | Composition for ophthalmological products |
-
2017
- 2017-02-15 EP EP17156331.5A patent/EP3363792A1/en not_active Ceased
-
2018
- 2018-02-14 EP EP18706232.8A patent/EP3583100B1/en active Active
- 2018-02-14 US US16/485,886 patent/US11040990B2/en active Active
- 2018-02-14 WO PCT/EP2018/053632 patent/WO2018149857A1/en unknown
- 2018-02-14 ES ES18706232T patent/ES2882714T3/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5290892A (en) | 1990-11-07 | 1994-03-01 | Nestle S.A. | Flexible intraocular lenses made from high refractive index polymers |
| US5331073A (en) | 1992-11-09 | 1994-07-19 | Allergan, Inc. | Polymeric compositions and intraocular lenses made from same |
| US5693095A (en) | 1995-06-07 | 1997-12-02 | Alcon Laboratories, Inc. | High refractive index ophthalmic lens materials |
| WO2006078834A1 (en) | 2005-01-21 | 2006-07-27 | Janssen Pharmaceutica N.V. | Novel heterocyclic benzo[c]chromene derivatives useful as modulators of the estrogen receptors |
| WO2007033831A1 (en) | 2005-09-23 | 2007-03-29 | Schmidt Intraocularlinsen Gmbh | Intraocular lens |
| WO2009074520A2 (en) | 2007-12-11 | 2009-06-18 | *Acri.Tec Gmbh | Copolymer and ophthalmological composition |
| WO2009074521A1 (en) | 2007-12-11 | 2009-06-18 | *Acri.Tec Gmbh | Ophthalmologic composition and use thereof |
| US20100324165A1 (en) | 2007-12-11 | 2010-12-23 | Helmut Ritter | Ophthalmological Composition And Use Thereof |
Non-Patent Citations (11)
| Title |
|---|
| J. M. G. COWIE, POLYMERS: CHEMISTRY & PHYSICS OF MODERN MATERIALS, 1991 |
| JEAN-MARC LEGEAIS, J CATARACT REFRACT SURG, vol. 24, 1998, pages 371 - 379 |
| M. SCHRAUB ET AL., EUROPEAN POLYMER JOURNAL, vol. 49, 2013, pages 1714 - 1721 |
| M. SCHRAUB ET AL., EUROPEAN POLYMER JOURNAL, vol. 51, 2014, pages 21 - 27 |
| M. SCHRAUB ET AL.: "Photoinduced refractive index changes of 3-phenyl-coumarin containing polymers for ophthalmic applications", EUROPEAN POLYMER JOURNAL, vol. 51, 1 December 2013 (2013-12-01), pages 21 - 27, XP028810223 * |
| PAC, vol. 68, 1996, pages 2291 |
| QIN ET AL., POLYMER INTERNATIONAL, vol. 48, 1999, pages 491 - 494 |
| SHASHIDHAR ET AL., J. MATER. CHEM., vol. 11, 2001, pages 2992 - 2995 |
| SIEGEL ET AL., J. AM. CHEM. SOC., vol. 120, 1998, pages 9680 - 9681 |
| SURATWALA ET AL., JOURNAL OF SOL-GEL SCIENCE AND TECHNOLOGY, vol. 8, 1997, pages 973 - 978 |
| SURATWALA T ET AL: "Photostability of silylated coumarin dyes in polyceram hosts", JOURNAL OF SOL-GEL SCIENCE AND TECHNOLOGY, SPRINGER, NEW YORK, NY, US, vol. 8, no. 1/03, 18 September 1997 (1997-09-18), pages 973 - 978, XP002109656, ISSN: 0928-0707, DOI: 10.1023/A:1018309718812 * |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11958819B2 (en) | 2015-08-21 | 2024-04-16 | Johnson & Johnson Surgical Vision, Inc. | Compounds for optically active devices |
| US11702396B2 (en) | 2017-02-15 | 2023-07-18 | Johnson & Johnson Surgical Vision, Inc. | Hydrophobic compounds for optically active devices |
| US11753387B2 (en) | 2017-02-15 | 2023-09-12 | Johnson & Johnson Surgical Vision, Inc. | Compounds for optically active devices |
| WO2020212543A1 (en) | 2019-04-18 | 2020-10-22 | Merck Patent Gmbh | Compounds for optically active devices |
| WO2020216928A1 (en) | 2019-04-26 | 2020-10-29 | Merck Patent Gmbh | System and method |
| EP4327779A2 (en) | 2019-04-26 | 2024-02-28 | AMO Ireland | System and method |
| WO2021233800A1 (en) | 2020-05-20 | 2021-11-25 | Merck Patent Gmbh | Azacoumarin and azathiocoumarin derivatives for use in optically active devices |
| WO2022012798A1 (en) | 2020-07-15 | 2022-01-20 | Merck Patent Gmbh | Optically active devices |
| WO2022012799A1 (en) | 2020-07-15 | 2022-01-20 | Merck Patent Gmbh | Optically active devices |
| WO2022128832A1 (en) | 2020-12-16 | 2022-06-23 | Merck Patent Gmbh | Optically active devices |
| EP4015512A1 (en) | 2020-12-16 | 2022-06-22 | AMO Ireland | Optically active devices |
| WO2022161895A1 (en) | 2021-01-27 | 2022-08-04 | AMO Ireland | Optically active devices |
| EP4036085A1 (en) | 2021-01-27 | 2022-08-03 | AMO Ireland | Compounds for optically active ophthalmic devices |
Also Published As
| Publication number | Publication date |
|---|---|
| EP3583100A1 (en) | 2019-12-25 |
| US11040990B2 (en) | 2021-06-22 |
| EP3363792A1 (en) | 2018-08-22 |
| US20200002363A1 (en) | 2020-01-02 |
| EP3583100B1 (en) | 2021-05-05 |
| ES2882714T3 (en) | 2021-12-02 |
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