BG108201A - Производни на n-(арилсулфонил)-бета-аминокиселини, съдържащи заместена аминоетилна група, метод за тяхното получаване и фармацевтични състави, които ги съдържат - Google Patents
Производни на n-(арилсулфонил)-бета-аминокиселини, съдържащи заместена аминоетилна група, метод за тяхното получаване и фармацевтични състави, които ги съдържат Download PDFInfo
- Publication number
- BG108201A BG108201A BG108201A BG10820103A BG108201A BG 108201 A BG108201 A BG 108201A BG 108201 A BG108201 A BG 108201A BG 10820103 A BG10820103 A BG 10820103A BG 108201 A BG108201 A BG 108201A
- Authority
- BG
- Bulgaria
- Prior art keywords
- compound
- group
- phenyl
- formula
- substituted
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims description 168
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 8
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 499
- 230000007170 pathology Effects 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 10
- 230000004054 inflammatory process Effects 0.000 claims abstract description 7
- 208000037976 chronic inflammation Diseases 0.000 claims abstract description 6
- 208000037893 chronic inflammatory disorder Diseases 0.000 claims abstract description 5
- 230000002085 persistent effect Effects 0.000 claims abstract description 5
- -1 phenylvinyl group Chemical group 0.000 claims description 401
- 238000000034 method Methods 0.000 claims description 103
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 80
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 33
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
- 125000005843 halogen group Chemical group 0.000 claims description 31
- 239000002253 acid Substances 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 125000002947 alkylene group Chemical group 0.000 claims description 24
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
- 239000013543 active substance Substances 0.000 claims description 18
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 17
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 17
- 150000004677 hydrates Chemical class 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 16
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 16
- 239000012453 solvate Substances 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 101800004538 Bradykinin Proteins 0.000 claims description 14
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 claims description 14
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 claims description 14
- 150000007522 mineralic acids Chemical class 0.000 claims description 14
- 150000007524 organic acids Chemical class 0.000 claims description 14
- 235000005985 organic acids Nutrition 0.000 claims description 14
- 125000002541 furyl group Chemical group 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims description 12
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 10
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 10
- 150000003254 radicals Chemical class 0.000 claims description 10
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 9
- 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 claims description 9
- 125000003386 piperidinyl group Chemical group 0.000 claims description 9
- 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 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000004791 2-fluoroethoxy group Chemical group FCCO* 0.000 claims description 6
- 206010061218 Inflammation Diseases 0.000 claims description 6
- 125000002393 azetidinyl group Chemical group 0.000 claims description 6
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 6
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 claims description 6
- 125000004534 benzothien-2-yl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 6
- 125000005507 decahydroisoquinolyl group Chemical group 0.000 claims description 6
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 5
- 125000005493 quinolyl group Chemical group 0.000 claims description 5
- 150000003461 sulfonyl halides Chemical class 0.000 claims description 5
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- DWKUKQRKVCMOLP-UHFFFAOYSA-O 1-piperideinium Chemical compound C1CC[NH+]=CC1 DWKUKQRKVCMOLP-UHFFFAOYSA-O 0.000 claims description 4
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- LTVOKYUPTHZZQH-UHFFFAOYSA-N difluoromethane Chemical group F[C]F LTVOKYUPTHZZQH-UHFFFAOYSA-N 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 4
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 4
- 125000004565 2,3-dihydrobenzofuran-4-yl group Chemical group O1CCC2=C1C=CC=C2* 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- CCAICKRNWJKLLH-UHFFFAOYSA-N N-methyl-2-phenyl-N-propan-2-ylpropanamide Chemical compound C1(=CC=CC=C1)C(C(=O)N(C)C(C)C)C CCAICKRNWJKLLH-UHFFFAOYSA-N 0.000 claims description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims description 2
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 2
- XYUPPXPJWYLXSW-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=C[CH]C2=C=COC2=C1 XYUPPXPJWYLXSW-UHFFFAOYSA-N 0.000 claims 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 102100035792 Kininogen-1 Human genes 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 102000005962 receptors Human genes 0.000 abstract description 16
- 108020003175 receptors Proteins 0.000 abstract description 16
- 102000010183 Bradykinin receptor Human genes 0.000 abstract description 9
- 108050001736 Bradykinin receptor Proteins 0.000 abstract description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 307
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 263
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 222
- 239000000243 solution Substances 0.000 description 207
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 186
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 171
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 164
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 146
- 239000000047 product Substances 0.000 description 136
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 119
- 239000002904 solvent Substances 0.000 description 110
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 96
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 94
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 84
- 239000011541 reaction mixture Substances 0.000 description 83
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 81
- 239000012074 organic phase Substances 0.000 description 78
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 70
- 238000003756 stirring Methods 0.000 description 68
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 55
- 239000000460 chlorine Substances 0.000 description 51
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 50
- 239000011734 sodium Substances 0.000 description 49
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 46
- 229920006395 saturated elastomer Polymers 0.000 description 43
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 41
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 37
- 239000008346 aqueous phase Substances 0.000 description 37
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- 239000000741 silica gel Substances 0.000 description 31
- 229910002027 silica gel Inorganic materials 0.000 description 31
- 125000004093 cyano group Chemical group *C#N 0.000 description 30
- 239000003921 oil Substances 0.000 description 27
- 239000002244 precipitate Substances 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 23
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 23
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
- 239000000706 filtrate Substances 0.000 description 21
- 229910052938 sodium sulfate Inorganic materials 0.000 description 21
- 235000011152 sodium sulphate Nutrition 0.000 description 21
- 125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 20
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- 239000002585 base Substances 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 150000001412 amines Chemical class 0.000 description 16
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 14
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 13
- 102400000967 Bradykinin Human genes 0.000 description 13
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 13
- 239000011347 resin Substances 0.000 description 13
- 229920005989 resin Polymers 0.000 description 13
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 12
- 230000002378 acidificating effect Effects 0.000 description 12
- 239000002609 medium Substances 0.000 description 12
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 11
- 238000002425 crystallisation Methods 0.000 description 11
- 230000008025 crystallization Effects 0.000 description 11
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 10
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
- 208000002193 Pain Diseases 0.000 description 10
- 239000007853 buffer solution Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- OPECTNGATDYLSS-UHFFFAOYSA-N naphthalene-2-sulfonyl chloride Chemical compound C1=CC=CC2=CC(S(=O)(=O)Cl)=CC=C21 OPECTNGATDYLSS-UHFFFAOYSA-N 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 9
- 230000009471 action Effects 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 8
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 7
- 238000001819 mass spectrum Methods 0.000 description 7
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- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 7
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
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- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000007868 Raney catalyst Substances 0.000 description 6
- 229910000564 Raney nickel Inorganic materials 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 6
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 229910052939 potassium sulfate Inorganic materials 0.000 description 6
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 6
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 6
- 239000012429 reaction media Substances 0.000 description 6
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
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- 244000309464 bull Species 0.000 description 5
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- 238000007796 conventional method Methods 0.000 description 5
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- 206010012601 diabetes mellitus Diseases 0.000 description 5
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- 238000000746 purification Methods 0.000 description 5
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- Biomedical Technology (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Immunology (AREA)
- Endocrinology (AREA)
- Otolaryngology (AREA)
- Reproductive Health (AREA)
- Vascular Medicine (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Psychiatry (AREA)
- Gastroenterology & Hepatology (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0104315A FR2822827B1 (fr) | 2001-03-28 | 2001-03-28 | Nouveaux derives de n-(arylsulfonyl) beta-aminoacides comportant un groupe aminomethyle substitue, leur procede de preparation et les compositions pharmaceutiques en contenant |
PCT/FR2002/001059 WO2002076964A1 (fr) | 2001-03-28 | 2002-03-27 | Derives de n-(arylsulfonyl)beta-aminoacides comportant un groupe aminomethyle substitue, leur procede de preparation et les compositions pharmaceutiques en contenant |
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Publication Number | Publication Date |
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BG108201A true BG108201A (bg) | 2004-09-30 |
Family
ID=8861734
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Application Number | Title | Priority Date | Filing Date |
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BG108201A BG108201A (bg) | 2001-03-28 | 2003-09-25 | Производни на n-(арилсулфонил)-бета-аминокиселини, съдържащи заместена аминоетилна група, метод за тяхното получаване и фармацевтични състави, които ги съдържат |
Country Status (38)
Country | Link |
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US (1) | US7157454B2 (is) |
EP (1) | EP1373233B1 (is) |
JP (1) | JP4188695B2 (is) |
KR (1) | KR100887038B1 (is) |
CN (1) | CN1297546C (is) |
AR (1) | AR033686A1 (is) |
AT (1) | ATE372329T1 (is) |
AU (1) | AU2002255077B2 (is) |
BG (1) | BG108201A (is) |
BR (1) | BR0208489A (is) |
CA (1) | CA2436225C (is) |
CY (1) | CY1106980T1 (is) |
CZ (1) | CZ301337B6 (is) |
DE (1) | DE60222248T2 (is) |
DK (1) | DK1373233T3 (is) |
EA (1) | EA006430B1 (is) |
EE (1) | EE05198B1 (is) |
ES (1) | ES2291464T3 (is) |
FR (1) | FR2822827B1 (is) |
HK (1) | HK1059931A1 (is) |
HR (1) | HRP20030748B1 (is) |
HU (1) | HUP0401538A3 (is) |
IL (3) | IL157215A0 (is) |
IS (1) | IS2582B (is) |
MA (1) | MA26995A1 (is) |
ME (1) | MEP25408A (is) |
MX (1) | MXPA03008756A (is) |
NO (1) | NO326519B1 (is) |
NZ (1) | NZ527429A (is) |
PL (1) | PL207553B1 (is) |
PT (1) | PT1373233E (is) |
RS (1) | RS52138B (is) |
SK (1) | SK286753B6 (is) |
TN (1) | TNSN03058A1 (is) |
TW (1) | TWI233923B (is) |
UA (1) | UA75906C2 (is) |
WO (1) | WO2002076964A1 (is) |
ZA (1) | ZA200306037B (is) |
Families Citing this family (37)
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PT1491540E (pt) * | 2001-03-30 | 2007-01-31 | Pfizer Prod Inc | Intermediários úteis na síntese de inibidores piridazinona de aldose reductase |
FR2840897B1 (fr) | 2002-06-14 | 2004-09-10 | Fournier Lab Sa | Nouveaux derives d'arylsulfonamides et leur utilisation en therapeutique |
AU2004231070B2 (en) | 2003-04-10 | 2008-02-14 | Amgen, Inc. | Bicyclic compounds having bradykinin receptors affinity and pharmaceutical compositions thereof |
WO2004099155A2 (en) * | 2003-05-02 | 2004-11-18 | Elan Pharmaceuticals, Inc. | 4-bromo-5-(2-chloro-benzoylamino)-1h-pyrazole-3-carboxylic acid (phenyl) amide derivates and related compounds as bradykinin b1 receptor antagonists for the treatment of inflamatory diseases |
TW200509910A (en) * | 2003-05-02 | 2005-03-16 | Elan Pharm Inc | Substituted pyrazole derivatives and related compounds as bradykinin B1 receptor antagonists |
US20070161633A1 (en) * | 2003-05-02 | 2007-07-12 | Elan Pharmaceuticals, Inc. | 4-Bromo-5-(2-chloro-benzoylamino)-1h-pyrazole-3-carboxylic acid (1-aminocarbonyl)eth-1-yl) amide derivatives and related compounds as bradykinin b1 receptor antagonists for the treatment of inflammatory diseases |
EP1654232A4 (en) * | 2003-08-07 | 2008-11-12 | Merck & Co Inc | N- (BIARYLMETHYL) AMINOCYCLOPROPANECARBOXAMIDES WITH SULFONYL SUBSTITUTION |
US7790754B2 (en) * | 2003-12-22 | 2010-09-07 | Merck Sharp & Dohme Corp. | Alpha-hydroxy amides as bradykinin antagonists or inverse agonists |
CA2580461A1 (en) * | 2004-09-23 | 2006-04-06 | Amgen Inc. | Substituted sulfonamidopropionamides and methods of use |
EP1856074A2 (en) * | 2004-10-06 | 2007-11-21 | Amgen, Inc | Substituted aryl or heteroarylsulfonylbutanamides for use as anti-inflammatory agents |
CA2583267A1 (en) | 2004-10-12 | 2006-04-27 | Amgen Inc. | Novel b1 bradykinin receptor antagonists |
US7612060B2 (en) | 2004-10-13 | 2009-11-03 | Amgen Inc. | Triazoles and methods of use |
WO2006071775A2 (en) * | 2004-12-29 | 2006-07-06 | Elan Pharmaceuticals, Inc. | Novel compounds useful for bradykinin b1 receptor antagonism |
EP1741444A1 (en) * | 2005-07-05 | 2007-01-10 | Jerini AG | Kinin antagonists for treating bladder dysfunction |
WO2007038116A1 (en) * | 2005-09-21 | 2007-04-05 | Dow Global Technologies Inc. | Process to prepare amino acid derivatives |
HU230518B1 (hu) | 2005-12-20 | 2016-10-28 | Richter Gedeon Nyrt. | Bradykinin B1 receptor szelektív antagonista hatással rendelkező új fenatridin származékok, eljárás előállításukra, és az ezeket tartalmazó gyógyszerkészítmények |
EP2086935A1 (de) | 2006-10-16 | 2009-08-12 | Grünenthal GmbH | Substituierte sulfonamid-derivate als bradykinin 1 rezeptor modulatoren |
HUP0600810A3 (en) | 2006-10-27 | 2008-09-29 | Richter Gedeon Nyrt | New sulfonamide derivatives as bradykinin antagonists, process and intermediates for their preparation and pharmaceutical compositions containing them |
HUP0600808A3 (en) * | 2006-10-27 | 2008-09-29 | Richter Gedeon Nyrt | New benzamide derivatives as bradykinin antagonists, process for their preparation and pharmaceutical compositions containing them |
HUP0600809A3 (en) * | 2006-10-27 | 2008-09-29 | Richter Gedeon Nyrt | New phenylsulfamoyl-benzamide derivatives as bradykinin antagonists, process and intermediates for their preparation and pharmaceutical compositions containing them |
FR2916352B1 (fr) * | 2007-05-23 | 2009-07-31 | Sanofi Aventis Sa | Utilisation d'un antagoniste non peptidique du recepteur b1 de la bradykinine pour la preparation de medicaments utiles pour la prevention ou le traitement de l'hypertension arterielle. |
WO2008153967A1 (en) * | 2007-06-08 | 2008-12-18 | Contec Therapeutics, Inc. | Bk1 antagonist conjugates |
FR2919803B1 (fr) * | 2007-08-07 | 2011-07-22 | Sanofi Aventis | Utilisation d'un antagoniste non peptidique du recepteur b1 pour la preparation de medicaments utiles pour le traitement de l'obesite et des pathologies liees a l'obesite ou au diabete |
MX2010004431A (es) * | 2007-10-27 | 2010-05-13 | Richter Gedeon Nyrt | Nuevos derivados no peptidicos como antagonistas b1 de la bradiquinina. |
US8318769B2 (en) * | 2008-04-08 | 2012-11-27 | Gruenethal Gmbh | Substituted sulfonamide compounds |
WO2010022304A1 (en) * | 2008-08-21 | 2010-02-25 | Forest Laboratories Holdings Limited | Methods for treating cns disorders |
EA201170351A1 (ru) * | 2008-08-21 | 2011-08-30 | Рихтер Гедеон Нирт. | Способы лечения невропатической боли |
HUP1000598A2 (en) | 2010-11-05 | 2012-09-28 | Richter Gedeon Nyrt | Indole derivatives |
AR097279A1 (es) | 2013-08-09 | 2016-03-02 | Actelion Pharmaceuticals Ltd | Derivados de benzimidazolil-metil urea como agonistas del receptor de alx |
JP6448498B2 (ja) * | 2015-08-04 | 2019-01-09 | 日本ゴア株式会社 | 回路基板製造プロセス液用精密フィルタ |
US11458142B2 (en) | 2017-08-25 | 2022-10-04 | The Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Compositions and methods for ameliorating pain |
JP7065951B2 (ja) | 2017-09-22 | 2022-05-12 | ジュビラント エピパッド エルエルシー | Pad阻害剤としての複素環式化合物 |
ES2941512T3 (es) | 2017-10-18 | 2023-05-23 | Jubilant Epipad LLC | Compuestos de imidazo-piridina como inhibidores de PAD |
CA3080677A1 (en) | 2017-11-06 | 2019-05-09 | Jubilant Prodel LLC | Pyrimidine derivatives as inhibitors of pd1/pd-l1 activation |
PL3704120T3 (pl) | 2017-11-24 | 2024-09-16 | Jubilant Episcribe Llc | Związki heterocykliczne jako inhibitory prmt5 |
CN112105610B (zh) | 2018-03-13 | 2024-01-26 | 朱比连特普罗德尔有限责任公司 | 作为pd1/pd-l1相互作用/活化的抑制剂的双环化合物 |
CN114075274B (zh) * | 2022-01-18 | 2022-04-12 | 浙江湃肽生物有限公司深圳分公司 | 一种索玛鲁肽类似物及其制备方法和用途 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5714497A (en) | 1993-02-15 | 1998-02-03 | Sanofi | Compounds bearing sulphamoyl and amidino radicals, their preparation process and pharmaceutical compositions containing them |
FR2701480B1 (fr) * | 1993-02-15 | 1995-05-24 | Sanofi Elf | Composés à groupe sulfamoyle et amidino, leur procédé de préparation et les compositions pharmaceutiques les contenant. |
FR2735128B1 (fr) * | 1995-06-07 | 1997-07-25 | Fournier Ind & Sante | Nouveaux composes de benzenesulfonamide, leur procede de preparation et utilisation en therapeutique. |
DE19548709A1 (de) * | 1995-12-23 | 1997-07-03 | Merck Patent Gmbh | Tyrosinderivate |
FR2743562B1 (fr) * | 1996-01-11 | 1998-04-03 | Sanofi Sa | Derives de n-(arylsulfonyl) aminoacides, leur preparation, les compositions pharmaceutiques en contenant |
CZ298814B6 (cs) * | 1996-01-23 | 2008-02-13 | Shionogi & Co., Ltd. | Sulfonované deriváty aminokyselin a metaloproteasové inhibitory obsahující tyto deriváty |
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2001
- 2001-03-28 FR FR0104315A patent/FR2822827B1/fr not_active Expired - Fee Related
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2002
- 2002-03-26 AR ARP020101096A patent/AR033686A1/es active IP Right Grant
- 2002-03-27 AU AU2002255077A patent/AU2002255077B2/en not_active Ceased
- 2002-03-27 HU HU0401538A patent/HUP0401538A3/hu not_active Application Discontinuation
- 2002-03-27 PL PL367242A patent/PL207553B1/pl unknown
- 2002-03-27 UA UA2003087628A patent/UA75906C2/uk unknown
- 2002-03-27 EA EA200300942A patent/EA006430B1/ru not_active IP Right Cessation
- 2002-03-27 TW TW091106017A patent/TWI233923B/zh not_active IP Right Cessation
- 2002-03-27 ME MEP-254/08A patent/MEP25408A/xx unknown
- 2002-03-27 AT AT02724383T patent/ATE372329T1/de active
- 2002-03-27 BR BR0208489-9A patent/BR0208489A/pt not_active Application Discontinuation
- 2002-03-27 ES ES02724383T patent/ES2291464T3/es not_active Expired - Lifetime
- 2002-03-27 TN TNPCT/FR2002/001059A patent/TNSN03058A1/fr unknown
- 2002-03-27 CN CNB028075390A patent/CN1297546C/zh not_active Expired - Fee Related
- 2002-03-27 US US10/472,674 patent/US7157454B2/en not_active Expired - Lifetime
- 2002-03-27 EP EP02724383A patent/EP1373233B1/fr not_active Expired - Lifetime
- 2002-03-27 NZ NZ527429A patent/NZ527429A/en not_active IP Right Cessation
- 2002-03-27 DK DK02724383T patent/DK1373233T3/da active
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- 2002-03-27 KR KR1020037012554A patent/KR100887038B1/ko not_active IP Right Cessation
- 2002-03-27 WO PCT/FR2002/001059 patent/WO2002076964A1/fr active IP Right Grant
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- 2002-03-27 JP JP2002576224A patent/JP4188695B2/ja not_active Expired - Fee Related
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- 2002-03-27 SK SK1204-2003A patent/SK286753B6/sk not_active IP Right Cessation
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