ZA200305684B - 2H-1-Benzopyran derivatives, processes for their preparation and pharmaceutical compositions thereof. - Google Patents

2H-1-Benzopyran derivatives, processes for their preparation and pharmaceutical compositions thereof. Download PDF

Info

Publication number: ZA200305684B
Authority: ZA; South Africa
Prior art keywords: alkyl; alkanoyl; compounds; aryloyl; formula
Prior art date: 2001-01-24

Application number

ZA200305684A

Other languages

English (en)

Inventor

Maurizio Delcanale

Gabriele Amari

Elisabetta Armani

Maurizio Civelli

Elisabetta Galbiati

Original Assignee

Chiesi Farma Spa

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2001-01-24

Filing date

2002-01-21

Publication date

2004-07-23

2002-01-21 Application filed by Chiesi Farma Spa filed Critical Chiesi Farma Spa

2004-07-23 Publication of ZA200305684B publication Critical patent/ZA200305684B/en

Links

238000002360 preparation method Methods 0.000 title claims abstract description 21
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 5
238000000034 method Methods 0.000 title abstract description 7
230000008569 process Effects 0.000 title abstract description 6
125000000850 2H-chromenyl group Chemical class O1C(C=CC2=CC=CC=C12)* 0.000 title abstract 2
230000007170 pathology Effects 0.000 claims abstract description 4
230000002265 prevention Effects 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 75
125000000217 alkyl group Chemical group 0.000 claims description 36
229910052799 carbon Inorganic materials 0.000 claims description 19
229910052739 hydrogen Inorganic materials 0.000 claims description 14
-1 aryloyl Chemical group 0.000 claims description 13
125000001589 carboacyl group Chemical group 0.000 claims description 12
125000003545 alkoxy group Chemical group 0.000 claims description 11
125000003118 aryl group Chemical group 0.000 claims description 11
125000005843 halogen group Chemical group 0.000 claims description 10
125000003342 alkenyl group Chemical group 0.000 claims description 9
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 8
125000002252 acyl group Chemical group 0.000 claims description 7
125000004429 atom Chemical group 0.000 claims description 7
125000004432 carbon atom Chemical group C* 0.000 claims description 7
150000000463 2H-chromenes Chemical class 0.000 claims description 6
125000001424 substituent group Chemical group 0.000 claims description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
229940011871 estrogen Drugs 0.000 claims description 5
239000000262 estrogen Substances 0.000 claims description 5
125000000262 haloalkenyl group Chemical group 0.000 claims description 5
125000001188 haloalkyl group Chemical group 0.000 claims description 5
229910052757 nitrogen Inorganic materials 0.000 claims description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
208000001132 Osteoporosis Diseases 0.000 claims description 4
WPJWYDWRUYBVGA-UHFFFAOYSA-N 4-benzylidene-2,3-dihydrochromene Chemical compound C12=CC=CC=C2OCCC1=CC1=CC=CC=C1 WPJWYDWRUYBVGA-UHFFFAOYSA-N 0.000 claims description 3
IQVYMVBVNVNDLK-UHFFFAOYSA-N C=1COC2=CC=CC=C2C=1CC1=CC=CC=C1 Chemical compound C=1COC2=CC=CC=C2C=1CC1=CC=CC=C1 IQVYMVBVNVNDLK-UHFFFAOYSA-N 0.000 claims description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
150000002148 esters Chemical class 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
206010028980 Neoplasm Diseases 0.000 claims description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
201000011510 cancer Diseases 0.000 claims description 2
125000001309 chloro group Chemical group Cl* 0.000 claims description 2
208000029078 coronary artery disease Diseases 0.000 claims description 2
230000001419 dependent effect Effects 0.000 claims description 2
239000003814 drug Substances 0.000 claims description 2
229910052731 fluorine Inorganic materials 0.000 claims description 2
239000011737 fluorine Substances 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims description 2
ZUDXUNPSRMREOJ-UHFFFAOYSA-N 3-(4-methoxyphenyl)-4-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]-2h-chromen-7-ol Chemical group C1=CC(OC)=CC=C1C(COC1=CC(O)=CC=C11)=C1CC(C=C1)=CC=C1OCCN1CCCCC1 ZUDXUNPSRMREOJ-UHFFFAOYSA-N 0.000 claims 1
QKFSKKROTLEPHN-UHFFFAOYSA-N 3-phenyl-4-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]-2h-chromen-7-ol Chemical group C=1C=CC=CC=1C=1COC2=CC(O)=CC=C2C=1CC(C=C1)=CC=C1OCCN1CCCCC1 QKFSKKROTLEPHN-UHFFFAOYSA-N 0.000 claims 1
239000004480 active ingredient Substances 0.000 claims 1
239000000546 pharmaceutical excipient Substances 0.000 claims 1
125000003386 piperidinyl group Chemical group 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
239000002904 solvent Substances 0.000 description 16
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
239000000203 mixture Substances 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
235000019439 ethyl acetate Nutrition 0.000 description 10
125000006239 protecting group Chemical group 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000007787 solid Substances 0.000 description 9
239000003054 catalyst Substances 0.000 description 7
239000000047 product Substances 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
239000002585 base Substances 0.000 description 6
238000009835 boiling Methods 0.000 description 6
238000003756 stirring Methods 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
210000001519 tissue Anatomy 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
238000003747 Grignard reaction Methods 0.000 description 5
150000001562 benzopyrans Chemical group 0.000 description 5
239000003208 petroleum Substances 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
239000000010 aprotic solvent Substances 0.000 description 4
235000019441 ethanol Nutrition 0.000 description 4
239000001257 hydrogen Substances 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
229910052784 alkaline earth metal Inorganic materials 0.000 description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
150000002576 ketones Chemical class 0.000 description 3
239000011777 magnesium Substances 0.000 description 3
229940087646 methanolamine Drugs 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
SUSQOBVLVYHIEX-UHFFFAOYSA-N o-phenylene-diaceto-nitrile Natural products N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 3
150000002989 phenols Chemical class 0.000 description 3
PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 description 2
SSIMHHUMYMHNID-UHFFFAOYSA-N 4-(chloromethyl)phenol Chemical compound OC1=CC=C(CCl)C=C1 SSIMHHUMYMHNID-UHFFFAOYSA-N 0.000 description 2
PJJGZPJJTHBVMX-UHFFFAOYSA-N 5,7-Dihydroxyisoflavone Chemical compound C=1C(O)=CC(O)=C(C2=O)C=1OC=C2C1=CC=CC=C1 PJJGZPJJTHBVMX-UHFFFAOYSA-N 0.000 description 2
206010065687 Bone loss Diseases 0.000 description 2
ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 2
235000019502 Orange oil Nutrition 0.000 description 2
JPYHHZQJCSQRJY-UHFFFAOYSA-N Phloroglucinol Natural products CCC=CCC=CCC=CCC=CCCCCC(=O)C1=C(O)C=C(O)C=C1O JPYHHZQJCSQRJY-UHFFFAOYSA-N 0.000 description 2
150000001266 acyl halides Chemical class 0.000 description 2
239000000556 agonist Substances 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
150000001342 alkaline earth metals Chemical class 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
230000003042 antagnostic effect Effects 0.000 description 2
230000009286 beneficial effect Effects 0.000 description 2
210000000988 bone and bone Anatomy 0.000 description 2
229910002091 carbon monoxide Inorganic materials 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
230000000694 effects Effects 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
150000004658 ketimines Chemical class 0.000 description 2
XZEUAXYWNKYKPL-WDYNHAJCSA-N levormeloxifene Chemical compound C1([C@H]2[C@@H](C3=CC=C(C=C3OC2(C)C)OC)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 XZEUAXYWNKYKPL-WDYNHAJCSA-N 0.000 description 2
229950002728 levormeloxifene Drugs 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
239000010502 orange oil Substances 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
QCDYQQDYXPDABM-UHFFFAOYSA-N phloroglucinol Chemical compound OC1=CC(O)=CC(O)=C1 QCDYQQDYXPDABM-UHFFFAOYSA-N 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 2
229960004622 raloxifene Drugs 0.000 description 2
238000006722 reduction reaction Methods 0.000 description 2
239000008259 solid foam Substances 0.000 description 2
YYFZIHWSVCQGLR-UHFFFAOYSA-N (5-hydroxy-4-oxo-3-phenyl-2,3-dihydrochromen-7-yl) 2,2-dimethylpropanoate Chemical compound C1OC2=CC(OC(=O)C(C)(C)C)=CC(O)=C2C(=O)C1C1=CC=CC=C1 YYFZIHWSVCQGLR-UHFFFAOYSA-N 0.000 description 1
YWABDXBMWCXDNY-UHFFFAOYSA-N (5-hydroxy-4-oxo-3-phenylchromen-7-yl) 2,2-dimethylpropanoate Chemical compound C=1C(OC(=O)C(C)(C)C)=CC(O)=C(C2=O)C=1OC=C2C1=CC=CC=C1 YWABDXBMWCXDNY-UHFFFAOYSA-N 0.000 description 1
KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical compound C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
VFLQQZCRHPIGJU-UHFFFAOYSA-N 1-(2-chloroethyl)piperidine;hydron;chloride Chemical compound Cl.ClCCN1CCCCC1 VFLQQZCRHPIGJU-UHFFFAOYSA-N 0.000 description 1
PDUKJODPFIFHNK-UHFFFAOYSA-N 1-[2-(4-bromophenoxy)ethyl]piperidine Chemical compound C1=CC(Br)=CC=C1OCCN1CCCCC1 PDUKJODPFIFHNK-UHFFFAOYSA-N 0.000 description 1
YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
HQALDKFFRYFTKP-UHFFFAOYSA-N 2-[4-[4-(2-benzyl-1-benzothiophen-3-yl)phenyl]-2-bromo-6-(3-methoxyphenyl)phenoxy]acetic acid Chemical compound COC1=CC=CC(C=2C(=C(Br)C=C(C=2)C=2C=CC(=CC=2)C=2C3=CC=CC=C3SC=2CC=2C=CC=CC=2)OCC(O)=O)=C1 HQALDKFFRYFTKP-UHFFFAOYSA-N 0.000 description 1
VADKRMSMGWJZCF-UHFFFAOYSA-N 2-bromophenol Chemical compound OC1=CC=CC=C1Br VADKRMSMGWJZCF-UHFFFAOYSA-N 0.000 description 1
SLHBRIIHMDJIBT-UHFFFAOYSA-N 2-phenyl-1-(2,4,6-trihydroxyphenyl)ethanone Chemical compound OC1=CC(O)=CC(O)=C1C(=O)CC1=CC=CC=C1 SLHBRIIHMDJIBT-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
AMHCKPXCBQCBHJ-UHFFFAOYSA-N Cl.C1OC2=CC(O)=CC(O)=C2C(C=2C=CC(OCCN3CCCCC3)=CC=2)=C1C1=CC=CC=C1 Chemical compound Cl.C1OC2=CC(O)=CC(O)=C2C(C=2C=CC(OCCN3CCCCC3)=CC=2)=C1C1=CC=CC=C1 AMHCKPXCBQCBHJ-UHFFFAOYSA-N 0.000 description 1
RWGRPTBDSWZJQB-UHFFFAOYSA-N Cl.C=1C(OC(=O)C(C)(C)C)=CC(O)=C(C2(O)C=3C=CC(OCCN4CCCCC4)=CC=3)C=1OCC2C1=CC=CC=C1 Chemical compound Cl.C=1C(OC(=O)C(C)(C)C)=CC(O)=C(C2(O)C=3C=CC(OCCN4CCCCC4)=CC=3)C=1OCC2C1=CC=CC=C1 RWGRPTBDSWZJQB-UHFFFAOYSA-N 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
229910010082 LiAlH Inorganic materials 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
MKYQPGPNVYRMHI-UHFFFAOYSA-N Triphenylethylene Chemical group C=1C=CC=CC=1C=C(C=1C=CC=CC=1)C1=CC=CC=C1 MKYQPGPNVYRMHI-UHFFFAOYSA-N 0.000 description 1
OCUIUJZUXNLSQT-UHFFFAOYSA-N [4-[7-(2,2-dimethylpropanoyloxy)-5-hydroxy-4-oxo-2,3-dihydrochromen-3-yl]phenyl] 2,2-dimethylpropanoate Chemical compound C1=CC(OC(=O)C(C)(C)C)=CC=C1C1C(=O)C2=C(O)C=C(OC(=O)C(C)(C)C)C=C2OC1 OCUIUJZUXNLSQT-UHFFFAOYSA-N 0.000 description 1
UESWPFFKFVVJQG-UHFFFAOYSA-N [5-hydroxy-3-phenyl-4-[4-(2-piperidin-1-ylethoxy)phenyl]-2H-chromen-7-yl] 2,2-dimethylpropanoate hydrochloride Chemical compound Cl.C1(=CC=CC=C1)C=1COC2=CC(=CC(=C2C1C1=CC=C(C=C1)OCCN1CCCCC1)O)OC(C(C)(C)C)=O UESWPFFKFVVJQG-UHFFFAOYSA-N 0.000 description 1
CEDJAONCJAXRDY-UHFFFAOYSA-N [5-hydroxy-3-phenyl-4-[4-(2-piperidin-1-ylethoxy)phenyl]-3,4-dihydro-2h-chromen-7-yl] 2,2-dimethylpropanoate;hydrochloride Chemical compound Cl.C1OC2=CC(OC(=O)C(C)(C)C)=CC(O)=C2C(C=2C=CC(OCCN3CCCCC3)=CC=2)C1C1=CC=CC=C1 CEDJAONCJAXRDY-UHFFFAOYSA-N 0.000 description 1
BKQYDDFUZHWBLD-UHFFFAOYSA-M [Br-].C1=CC([Mg+])=CC=C1OCCN1CCCCC1 Chemical compound [Br-].C1=CC([Mg+])=CC=C1OCCN1CCCCC1 BKQYDDFUZHWBLD-UHFFFAOYSA-M 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
239000002253 acid Substances 0.000 description 1
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150000001348 alkyl chlorides Chemical class 0.000 description 1
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239000005557 antagonist Substances 0.000 description 1
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238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
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238000002425 crystallisation Methods 0.000 description 1
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238000003821 enantio-separation Methods 0.000 description 1
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239000002834 estrogen receptor modulator Substances 0.000 description 1
102000015694 estrogen receptors Human genes 0.000 description 1
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230000001076 estrogenic effect Effects 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
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TZBJGXHYKVUXJN-UHFFFAOYSA-N genistein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O TZBJGXHYKVUXJN-UHFFFAOYSA-N 0.000 description 1
SLRCCWJSBJZJBV-BYNSBNAKSA-N genisteine Chemical compound C1N2CCCC[C@@H]2[C@@H]2CN3CCCC[C@@H]3[C@H]1C2 SLRCCWJSBJZJBV-BYNSBNAKSA-N 0.000 description 1
150000004795 grignard reagents Chemical class 0.000 description 1
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125000000623 heterocyclic group Chemical group 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
238000003760 magnetic stirring Methods 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
XZEUAXYWNKYKPL-URLMMPGGSA-N ormeloxifene Chemical compound C1([C@@H]2[C@H](C3=CC=C(C=C3OC2(C)C)OC)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 XZEUAXYWNKYKPL-URLMMPGGSA-N 0.000 description 1
229960003327 ormeloxifene Drugs 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
229960001553 phloroglucinol Drugs 0.000 description 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000001850 reproductive effect Effects 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
229910052707 ruthenium Inorganic materials 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
230000003637 steroidlike Effects 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
239000000126 substance Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003509 tertiary alcohols Chemical class 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
238000002525 ultrasonication Methods 0.000 description 1
210000004291 uterus Anatomy 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1

Classifications

- 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
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/32—Antioestrogens

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

ZA200305684A 2001-01-24 2002-01-21 2H-1-Benzopyran derivatives, processes for their preparation and pharmaceutical compositions thereof. ZA200305684B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP01101521A EP1229036B1 (de)	2001-01-24	2001-01-24	2H-1-Benzopyran-Derivative, Prozesse zu ihrer Herstellung und Pharmazeutische Zusammensetzungen

Publications (1)

Publication Number	Publication Date
ZA200305684B true ZA200305684B (en)	2004-07-23

Family

ID=8176283

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200305684A ZA200305684B (en)	2001-01-24	2002-01-21	2H-1-Benzopyran derivatives, processes for their preparation and pharmaceutical compositions thereof.

Country Status (5)

Country	Link
EP (1)	EP1229036B1 (de)
AT (1)	ATE286893T1 (de)
DE (1)	DE60108354T2 (de)
ES (1)	ES2236056T3 (de)
ZA (1)	ZA200305684B (de)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP3052482A1 (de)	2013-09-30	2016-08-10	Polfarmex S.A.	Neuartige substituierte n,n-dimethylaminoalkylether von isoflavanonoximen als h1-rezeptor-antagonisten
MX2018009908A (es)	2016-02-15	2018-09-07	Sanofi Sa	Derivados de 6,7-dihidro-5h-benzo[7]anuleno como moduladores de receptores de estrogenos.
JP6946430B2 (ja) *	2016-11-17	2021-10-06	サノフイＳａｎｏｆｉ	新規の置換ｎ−（３−フルオロプロピル）−ピロリジン化合物、それを製造するための方法、およびその治療的使用
EP3434272A1 (de)	2017-07-25	2019-01-30	Sanofi	Kombination aus palbociclib und 6-(2,4-dichlorophenyl)-5-[4-[(3s)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7h-benzo[7]annulen-2-carboxylsäure
AU2019335542A1 (en)	2018-09-07	2021-04-01	Sanofi	Process for the preparation of methyl 6-(2,4-dichlorophenyl)-5-(4-((3s)-1-(3-fluoropropyl)pyrrolidin-3-yl)oxyphenyl)-8,9-dihydro-7H-benzo(7)annulene-2-carboxylate
CN117924262A (zh) *	2022-10-14	2024-04-26	中国科学院上海药物研究所	二氢苯并噻喃类衍生物及其制备方法和用途

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5280040A (en) *	1993-03-11	1994-01-18	Zymogenetics, Inc.	Methods for reducing bone loss using centchroman derivatives
US5985306A (en) *	1996-10-28	1999-11-16	Novo Nordisk A/S	(+)-enantiomers of cis-3,4-chroman derivatives useful in prevention or treatment of estrogen diseases or syndromes
KR19980064120A (ko) *	1996-12-13	1998-10-07	김정규	신규한 벤조피란 유도체
WO2000039120A2 (en) *	1998-12-30	2000-07-06	Signal Pharmaceuticals, Inc.	Compounds and methods for modulation of estrogen receptors

2001
- 2001-01-24 EP EP01101521A patent/EP1229036B1/de not_active Expired - Lifetime
- 2001-01-24 DE DE60108354T patent/DE60108354T2/de not_active Expired - Lifetime
- 2001-01-24 AT AT01101521T patent/ATE286893T1/de not_active IP Right Cessation
- 2001-01-24 ES ES01101521T patent/ES2236056T3/es not_active Expired - Lifetime
2002
- 2002-01-21 ZA ZA200305684A patent/ZA200305684B/en unknown

Also Published As

Publication number	Publication date
DE60108354T2 (de)	2006-01-05
DE60108354D1 (de)	2005-02-17
EP1229036A1 (de)	2002-08-07
EP1229036B1 (de)	2005-01-12
ES2236056T3 (es)	2005-07-16
ATE286893T1 (de)	2005-01-15

Publication	Publication Date	Title
US7960573B2 (en)	2011-06-14	Method for enantioselective hydrogenation of chromenes
EP1076653B1 (de)	2004-09-29	Selektiv auf den cb2-rezeptor wirkende cannabinoide
ES2391865T3 (es)	2012-11-30	Nuevos derivados de 1,2-dihidroquinolina que tienen un grupo fenilamino alquilo inferior y un grupo fenilo introducido por éster como sustituyentes
JP2942630B2 (ja)	1999-08-30	ロイコトリエンｂ▲下４▼アンタゴニスト
JPH04502322A (ja)	1992-04-23	抗アテローム性動脈硬化症性および抗血栓性１―ベンゾピラン―４―オン類および２―アミノ―１，３―ベンゾオキサジン―４―オン類
KR900007781B1 (ko)	1990-10-20	융합된 벤즈아제핀
AU2002237282B2 (en)	2007-02-15	2H-1-Benzopyran derivatives, processes for their preparation and pharmaceutical compositions thereof
AU2002237282A1 (en)	2003-02-06	2H-1-Benzopyran derivatives, processes for their preparation and pharmaceutical compositions thereof
ZA200305684B (en)	2004-07-23	2H-1-Benzopyran derivatives, processes for their preparation and pharmaceutical compositions thereof.
CA2022236A1 (en)	1991-02-01	Coumarin derivatives, their preparation and their use in the treatment of cerebrovascular disorders
HU177798B (en)	1981-12-28	Process for producing substituted pyrrolydines
AU629258B2 (en)	1992-10-01	Aryloxy-, arylthio-, heteroaryloxy-, heteroarylthio- alkenylene derivatives of amines
JP2790335B2 (ja)	1998-08-27	共役γ―オキシブテノライド化合物およびこれを有効成分とする抗潰瘍剤
CA2019621A1 (en)	1990-12-23	Arylalkylamine derivatives
CN100548990C (zh)	2009-10-14	苯并咪唑衍生物的制备方法
FI88158B (fi)	1992-12-31	Foerfarande foer framstaellning av nya terapeutiskt anvaendbara bicykliska bensofusionerade foereningar
CA1341011C (en)	2000-05-30	Benzo-fused cycloalkane and oxa- and thia-, cycloalkane trans-1,2-diamine derivatives
JPH0532657A (ja)	1993-02-09	新規ベンゾジオキソール誘導体およびこれを含有する肝障害改善剤