CA2176130A1 - Antagonistes non peptidiques des recepteurs des tachykinines - Google Patents
Antagonistes non peptidiques des recepteurs des tachykininesInfo
- Publication number
- CA2176130A1 CA2176130A1 CA002176130A CA2176130A CA2176130A1 CA 2176130 A1 CA2176130 A1 CA 2176130A1 CA 002176130 A CA002176130 A CA 002176130A CA 2176130 A CA2176130 A CA 2176130A CA 2176130 A1 CA2176130 A1 CA 2176130A1
- Authority
- CA
- Canada
- Prior art keywords
- ethoxy
- benzoyl
- phenyl
- methoxyphenyl
- benzo
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
- 239000002462 tachykinin receptor antagonist Substances 0.000 title abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 200
- 102000003141 Tachykinin Human genes 0.000 claims abstract description 7
- 108060008037 tachykinin Proteins 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims description 59
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 47
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 43
- -1 piperazino Chemical group 0.000 claims description 37
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 36
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 30
- 239000004480 active ingredient Substances 0.000 claims description 28
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 26
- 125000005605 benzo group Chemical group 0.000 claims description 22
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 239000001257 hydrogen Chemical group 0.000 claims description 18
- 125000003870 2-(1-piperidinyl)ethoxy group Chemical group [*]OC([H])([H])C([H])([H])N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- PEJPCPSPGMHTQW-UHFFFAOYSA-N [6-butylsulfonyl-2-(4-butylsulfonylphenyl)-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(S(=O)(=O)CCCC)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(S(=O)(=O)CCCC)C=C2S1 PEJPCPSPGMHTQW-UHFFFAOYSA-N 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- OQUWGQXCYVDBCY-UHFFFAOYSA-N [4-[2-(dimethylamino)ethoxy]phenyl]-[6-methoxy-2-(4-methoxyphenyl)-1-benzofuran-3-yl]methanone Chemical compound C1=CC(OC)=CC=C1C1=C(C(=O)C=2C=CC(OCCN(C)C)=CC=2)C2=CC=C(OC)C=C2O1 OQUWGQXCYVDBCY-UHFFFAOYSA-N 0.000 claims description 4
- JCDOLTDJNBOLLR-UHFFFAOYSA-N [6-methoxy-2-(4-methoxyphenyl)-1-benzofuran-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(OC)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(OC)C=C2O1 JCDOLTDJNBOLLR-UHFFFAOYSA-N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- VVTOZHSGDQNHDR-UHFFFAOYSA-N [2-(4-methoxyphenyl)-3,4-dihydronaphthalen-1-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(OC)=CC=C1C(CCC1=CC=CC=C11)=C1C(=O)C(C=C1)=CC=C1OCCN1CCCCC1 VVTOZHSGDQNHDR-UHFFFAOYSA-N 0.000 claims description 3
- MBYVDLPFKVKFSH-UHFFFAOYSA-N [4-[2-(dimethylamino)ethoxy]phenyl]-[2-(4-methoxyphenyl)-3,4-dihydronaphthalen-1-yl]methanone Chemical compound C1=CC(OC)=CC=C1C(CCC1=CC=CC=C11)=C1C(=O)C1=CC=C(OCCN(C)C)C=C1 MBYVDLPFKVKFSH-UHFFFAOYSA-N 0.000 claims description 3
- WKLPUFDPOWRQHW-UHFFFAOYSA-N [4-[2-(dimethylamino)ethoxy]phenyl]-[6-hydroxy-2-(4-hydroxyphenyl)-1-benzofuran-3-yl]methanone Chemical compound C1=CC(OCCN(C)C)=CC=C1C(=O)C1=C(C=2C=CC(O)=CC=2)OC2=CC(O)=CC=C12 WKLPUFDPOWRQHW-UHFFFAOYSA-N 0.000 claims description 3
- PFQKWRCZNBMEQN-UHFFFAOYSA-N [4-[2-[di(propan-2-yl)amino]ethoxy]phenyl]-[6-methoxy-2-(4-methoxyphenyl)-1-benzofuran-3-yl]methanone Chemical compound C1=CC(OC)=CC=C1C1=C(C(=O)C=2C=CC(OCCN(C(C)C)C(C)C)=CC=2)C2=CC=C(OC)C=C2O1 PFQKWRCZNBMEQN-UHFFFAOYSA-N 0.000 claims description 3
- UGXIVUAIHKSJPN-UHFFFAOYSA-N [6-butylsulfonyl-2-(4-butylsulfonylphenyl)-1-benzothiophen-3-yl]-[4-(3-piperidin-1-ylpropoxy)phenyl]methanone Chemical compound C1=CC(S(=O)(=O)CCCC)=CC=C1C1=C(C(=O)C=2C=CC(OCCCN3CCCCC3)=CC=2)C2=CC=C(S(=O)(=O)CCCC)C=C2S1 UGXIVUAIHKSJPN-UHFFFAOYSA-N 0.000 claims description 3
- RGYQIOOSBFCBCU-UHFFFAOYSA-N [6-butylsulfonyl-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone Chemical compound C=1C=C(O)C=CC=1C=1SC2=CC(S(=O)(=O)CCCC)=CC=C2C=1C(=O)C(C=C1)=CC=C1OCCN1CCCCC1 RGYQIOOSBFCBCU-UHFFFAOYSA-N 0.000 claims description 3
- WDCPJTSXWJFXGJ-UHFFFAOYSA-N [6-hexylsulfonyl-2-(4-hexylsulfonylphenyl)-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(S(=O)(=O)CCCCCC)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(S(=O)(=O)CCCCCC)C=C2S1 WDCPJTSXWJFXGJ-UHFFFAOYSA-N 0.000 claims description 3
- KLDDBCNMLWXGSD-UHFFFAOYSA-N [6-hydroxy-2-(4-hydroxyphenyl)-1-benzofuran-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2O1 KLDDBCNMLWXGSD-UHFFFAOYSA-N 0.000 claims description 3
- HEXLJTVUDDKDOS-UHFFFAOYSA-N [6-methoxy-2-(4-methoxyphenyl)-1-benzofuran-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(OC)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCC3)=CC=2)C2=CC=C(OC)C=C2O1 HEXLJTVUDDKDOS-UHFFFAOYSA-N 0.000 claims description 3
- BUTBEWXLQVDMBT-UHFFFAOYSA-N [6-pentylsulfonyl-2-(4-pentylsulfonylphenyl)-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(S(=O)(=O)CCCCC)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(S(=O)(=O)CCCCC)C=C2S1 BUTBEWXLQVDMBT-UHFFFAOYSA-N 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 3
- DWQHXHINSNUITH-UHFFFAOYSA-N (6-methoxy-2-phenyl-3,4-dihydronaphthalen-1-yl)-[4-(2-pyrrolidin-1-ylethoxy)phenyl]methanone Chemical compound C=1C=CC=CC=1C=1CCC2=CC(OC)=CC=C2C=1C(=O)C(C=C1)=CC=C1OCCN1CCCC1 DWQHXHINSNUITH-UHFFFAOYSA-N 0.000 claims description 2
- RDFQQLFSBGBRFL-UHFFFAOYSA-N [1-ethyl-6-methoxy-2-(4-methoxyphenyl)indol-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone Chemical compound C12=CC=C(OC)C=C2N(CC)C(C=2C=CC(OC)=CC=2)=C1C(=O)C(C=C1)=CC=C1OCCN1CCCCC1 RDFQQLFSBGBRFL-UHFFFAOYSA-N 0.000 claims description 2
- ROHAVRDFSZPOLD-UHFFFAOYSA-N [2-(4-butylsulfonylphenyl)-6-hydroxy-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(S(=O)(=O)CCCC)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 ROHAVRDFSZPOLD-UHFFFAOYSA-N 0.000 claims description 2
- LIRXDTIOUUGHAD-UHFFFAOYSA-N [2-(4-chlorophenyl)-1-oxo-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(Cl)=CC=C1C(S(C1=CC=CC=C11)=O)=C1C(=O)C(C=C1)=CC=C1OCCN1CCCCC1 LIRXDTIOUUGHAD-UHFFFAOYSA-N 0.000 claims description 2
- VMLOZOVWOJFVFI-UHFFFAOYSA-N [2-(4-chlorophenyl)-1-oxo-1-benzothiophen-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(Cl)=CC=C1C(S(C1=CC=CC=C11)=O)=C1C(=O)C(C=C1)=CC=C1OCCN1CCCC1 VMLOZOVWOJFVFI-UHFFFAOYSA-N 0.000 claims description 2
- DDKPDPUZGNMJQR-UHFFFAOYSA-N [4-[2-(diethylamino)ethoxy]phenyl]-[2-(4-methoxyphenyl)-3,4-dihydronaphthalen-1-yl]methanone Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(=O)C1=C(C=2C=CC(OC)=CC=2)CCC2=CC=CC=C12 DDKPDPUZGNMJQR-UHFFFAOYSA-N 0.000 claims description 2
- QTWMDADOCIWMCJ-UHFFFAOYSA-N [4-[2-(diethylamino)ethoxy]phenyl]-[6-methoxy-2-(4-methoxyphenyl)-1-benzofuran-3-yl]methanone Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(=O)C1=C(C=2C=CC(OC)=CC=2)OC2=CC(OC)=CC=C12 QTWMDADOCIWMCJ-UHFFFAOYSA-N 0.000 claims description 2
- XHDXDYFMIWMSNC-UHFFFAOYSA-N [4-[2-[di(propan-2-yl)amino]ethoxy]phenyl]-[2-(4-methoxyphenyl)-3,4-dihydronaphthalen-1-yl]methanone Chemical compound C1=CC(OC)=CC=C1C(CCC1=CC=CC=C11)=C1C(=O)C1=CC=C(OCCN(C(C)C)C(C)C)C=C1 XHDXDYFMIWMSNC-UHFFFAOYSA-N 0.000 claims description 2
- FMNWSASOWARPII-UHFFFAOYSA-N [6-methoxy-2-(4-methoxyphenyl)-3,4-dihydronaphthalen-1-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(OC)=CC=C1C(CCC1=CC(OC)=CC=C11)=C1C(=O)C(C=C1)=CC=C1OCCN1CCCCC1 FMNWSASOWARPII-UHFFFAOYSA-N 0.000 claims description 2
- PXIYAHHRGDULQZ-UHFFFAOYSA-N n-(4-chlorophenyl)-2-[4-[(4-chlorophenyl)carbamoyl]phenyl]-3-[4-(2-piperidin-1-ylethoxy)benzoyl]-1-benzothiophene-6-carboxamide Chemical compound C1=CC(Cl)=CC=C1NC(=O)C1=CC=C(C2=C(C3=CC=C(C=C3S2)C(=O)NC=2C=CC(Cl)=CC=2)C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C=C1 PXIYAHHRGDULQZ-UHFFFAOYSA-N 0.000 claims description 2
- AQULBTVAGMUVBW-UHFFFAOYSA-N n-ethyl-2-[4-(ethylcarbamoyl)phenyl]-3-[4-(2-piperidin-1-ylethoxy)benzoyl]-1-benzothiophene-6-carboxamide Chemical compound C1=CC(C(=O)NCC)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(C(=O)NCC)C=C2S1 AQULBTVAGMUVBW-UHFFFAOYSA-N 0.000 claims description 2
- VRNHFNDTPNOMBL-UHFFFAOYSA-N n-methyl-2-[4-(methylcarbamoyl)phenyl]-3-[4-(2-piperidin-1-ylethoxy)benzoyl]-1-benzothiophene-6-carboxamide Chemical compound C1=CC(C(=O)NC)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(C(=O)NC)C=C2S1 VRNHFNDTPNOMBL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- DFFQPZGSIJARKY-UHFFFAOYSA-N [1-ethyl-6-hydroxy-2-(4-methoxyphenyl)indol-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone Chemical compound C12=CC=C(O)C=C2N(CC)C(C=2C=CC(OC)=CC=2)=C1C(=O)C(C=C1)=CC=C1OCCN1CCCCC1 DFFQPZGSIJARKY-UHFFFAOYSA-N 0.000 claims 2
- NUGMASFBOWUCCG-UHFFFAOYSA-N [4-[2-(diethylamino)ethoxy]phenyl]-[6-hydroxy-2-(4-hydroxyphenyl)-1-benzofuran-3-yl]methanone Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(=O)C1=C(C=2C=CC(O)=CC=2)OC2=CC(O)=CC=C12 NUGMASFBOWUCCG-UHFFFAOYSA-N 0.000 claims 2
- KXZSAUJSSPFLEK-UHFFFAOYSA-N [4-[2-[di(propan-2-yl)amino]ethoxy]phenyl]-[6-hydroxy-2-(4-hydroxyphenyl)-1-benzofuran-3-yl]methanone Chemical compound C1=CC(OCCN(C(C)C)C(C)C)=CC=C1C(=O)C1=C(C=2C=CC(O)=CC=2)OC2=CC(O)=CC=C12 KXZSAUJSSPFLEK-UHFFFAOYSA-N 0.000 claims 2
- RJPCXHINTJKOPW-UHFFFAOYSA-N [6-hydroxy-2-(4-hydroxyphenyl)-1-benzofuran-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCC3)=CC=2)C2=CC=C(O)C=C2O1 RJPCXHINTJKOPW-UHFFFAOYSA-N 0.000 claims 2
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 claims 2
- UXCMHGFKLPQEIY-UHFFFAOYSA-N 3-[4-(2-piperidin-1-ylethoxy)benzoyl]-n-propan-2-yl-2-[4-(propan-2-ylcarbamoyl)phenyl]-1-benzothiophene-6-carboxamide Chemical compound C1=CC(C(=O)NC(C)C)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(C(=O)NC(C)C)C=C2S1 UXCMHGFKLPQEIY-UHFFFAOYSA-N 0.000 claims 1
- UAUVDTRIPPZZCC-UHFFFAOYSA-N [2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=CC=C2S1 UAUVDTRIPPZZCC-UHFFFAOYSA-N 0.000 claims 1
- SEZLKRUKAYSYCE-UHFFFAOYSA-N [2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCC3)=CC=2)C2=CC=CC=C2S1 SEZLKRUKAYSYCE-UHFFFAOYSA-N 0.000 claims 1
- ZWLCVOFWYYZDLF-UHFFFAOYSA-N [2-(4-hydroxyphenyl)-3,4-dihydronaphthalen-1-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(O)=CC=C1C(CCC1=CC=CC=C11)=C1C(=O)C(C=C1)=CC=C1OCCN1CCCC1 ZWLCVOFWYYZDLF-UHFFFAOYSA-N 0.000 claims 1
- DTOKARZKAYFVFE-UHFFFAOYSA-N [2-(4-methoxyphenyl)-1-benzothiophen-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(OC)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCC3)=CC=2)C2=CC=CC=C2S1 DTOKARZKAYFVFE-UHFFFAOYSA-N 0.000 claims 1
- RXTALSIUEQVTBJ-UHFFFAOYSA-N [2-(4-methoxyphenyl)-1-benzothiophen-3-yl]-[4-(3-piperidin-1-ylpropoxy)phenyl]methanone Chemical compound C1=CC(OC)=CC=C1C1=C(C(=O)C=2C=CC(OCCCN3CCCCC3)=CC=2)C2=CC=CC=C2S1 RXTALSIUEQVTBJ-UHFFFAOYSA-N 0.000 claims 1
- CTCDPDLDXQMVHI-UHFFFAOYSA-N [4-[2-(diethylamino)ethoxy]phenyl]-[2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]methanone Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(=O)C1=C(C=2C=CC(O)=CC=2)SC2=CC=CC=C12 CTCDPDLDXQMVHI-UHFFFAOYSA-N 0.000 claims 1
- VPNDIBNQEWHOOO-UHFFFAOYSA-N [4-[2-(diethylamino)ethoxy]phenyl]-[2-(4-methoxyphenyl)-1-benzothiophen-3-yl]methanone Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(=O)C1=C(C=2C=CC(OC)=CC=2)SC2=CC=CC=C12 VPNDIBNQEWHOOO-UHFFFAOYSA-N 0.000 claims 1
- LZRVYDUXPBPSJL-UHFFFAOYSA-N [4-[2-(dimethylamino)ethoxy]phenyl]-[2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]methanone Chemical compound C1=CC(OCCN(C)C)=CC=C1C(=O)C1=C(C=2C=CC(O)=CC=2)SC2=CC=CC=C12 LZRVYDUXPBPSJL-UHFFFAOYSA-N 0.000 claims 1
- SDHGXWSAXQECTD-UHFFFAOYSA-N [4-[2-(dimethylamino)ethoxy]phenyl]-[2-(4-methoxyphenyl)-1-benzothiophen-3-yl]methanone Chemical compound C1=CC(OC)=CC=C1C1=C(C(=O)C=2C=CC(OCCN(C)C)=CC=2)C2=CC=CC=C2S1 SDHGXWSAXQECTD-UHFFFAOYSA-N 0.000 claims 1
- KRHFIZQFYADCRO-UHFFFAOYSA-N [4-[2-[di(propan-2-yl)amino]ethoxy]phenyl]-[2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]methanone Chemical compound C1=CC(OCCN(C(C)C)C(C)C)=CC=C1C(=O)C1=C(C=2C=CC(O)=CC=2)SC2=CC=CC=C12 KRHFIZQFYADCRO-UHFFFAOYSA-N 0.000 claims 1
- WDIONCKZCVBMKG-UHFFFAOYSA-N [4-[2-[di(propan-2-yl)amino]ethoxy]phenyl]-[2-(4-methoxyphenyl)-1-benzothiophen-3-yl]methanone Chemical compound C1=CC(OC)=CC=C1C1=C(C(=O)C=2C=CC(OCCN(C(C)C)C(C)C)=CC=2)C2=CC=CC=C2S1 WDIONCKZCVBMKG-UHFFFAOYSA-N 0.000 claims 1
- BAZWLFUEIINVTH-UHFFFAOYSA-N [6-butylsulfonyl-2-(4-butylsulfonylphenyl)-1-benzothiophen-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(S(=O)(=O)CCCC)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCC3)=CC=2)C2=CC=C(S(=O)(=O)CCCC)C=C2S1 BAZWLFUEIINVTH-UHFFFAOYSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 138
- 238000000034 method Methods 0.000 abstract description 40
- 238000009472 formulation Methods 0.000 abstract description 16
- 150000001907 coumarones Chemical class 0.000 abstract description 10
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 8
- 150000002475 indoles Chemical class 0.000 abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 189
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 72
- 239000011541 reaction mixture Substances 0.000 description 72
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 69
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 68
- 229940093499 ethyl acetate Drugs 0.000 description 63
- 235000019439 ethyl acetate Nutrition 0.000 description 63
- 239000003921 oil Substances 0.000 description 59
- 235000019198 oils Nutrition 0.000 description 59
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- GCMBDYZJVNESMC-UHFFFAOYSA-N n-phenyl-2-[4-(phenylcarbamoyl)phenyl]-3-[4-(2-piperidin-1-ylethoxy)benzoyl]-1-benzothiophene-6-carboxamide Chemical compound C=1C=C(C2=C(C3=CC=C(C=C3S2)C(=O)NC=2C=CC=CC=2)C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C=CC=1C(=O)NC1=CC=CC=C1 GCMBDYZJVNESMC-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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- BNZYBNYNPXKWCM-UHFFFAOYSA-N phenyl 4-methoxybenzoate Chemical compound C1=CC(OC)=CC=C1C(=O)OC1=CC=CC=C1 BNZYBNYNPXKWCM-UHFFFAOYSA-N 0.000 description 1
- FCJSHPDYVMKCHI-UHFFFAOYSA-N phenyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OC1=CC=CC=C1 FCJSHPDYVMKCHI-UHFFFAOYSA-N 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 229950009215 phenylbutanoic acid Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical group 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- KJRCEJOSASVSRA-UHFFFAOYSA-N propane-2-thiol Chemical compound CC(C)S KJRCEJOSASVSRA-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005470 propylenyl group Chemical group 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000012058 sterile packaged powder Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
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- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- ADNPLDHMAVUMIW-CUZNLEPHSA-N substance P Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 ADNPLDHMAVUMIW-CUZNLEPHSA-N 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000003375 sulfoxide group Chemical group 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- LJJKNPQAGWVLDQ-SNVBAGLBSA-N thiorphan Chemical compound OC(=O)CNC(=O)[C@@H](CS)CC1=CC=CC=C1 LJJKNPQAGWVLDQ-SNVBAGLBSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 230000002455 vasospastic effect Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 201000005539 vernal conjunctivitis Diseases 0.000 description 1
- 208000009935 visceral pain Diseases 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229940071104 xylenesulfonate Drugs 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/80—Radicals substituted by oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
- Indole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
La présente invention décrit une série de benzofurannes et d'indoles substitués utiles comme antagonistes non peptidiques des récepteurs des tachykinines. Elle décrit également des procédés pour traiter ou prévenir des états pathologiques associés à un excès de tachykinines. Ces procédés consistent à administrer un ou plusieurs des composés décrits ainsi que des formulations les mettant en oeuvre.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17113493A | 1993-12-21 | 1993-12-21 | |
| US08/171,134 | 1993-12-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2176130A1 true CA2176130A1 (fr) | 1995-06-29 |
Family
ID=22622667
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002176130A Abandoned CA2176130A1 (fr) | 1993-12-21 | 1994-12-14 | Antagonistes non peptidiques des recepteurs des tachykinines |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0736007A4 (fr) |
| JP (1) | JPH09506898A (fr) |
| AU (1) | AU1339795A (fr) |
| CA (1) | CA2176130A1 (fr) |
| MX (1) | MXPA99001870A (fr) |
| WO (1) | WO1995017382A1 (fr) |
| ZA (1) | ZA9410040B (fr) |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5492927A (en) * | 1993-12-21 | 1996-02-20 | Eli Lilly And Company | Non-peptide tachykinin receptor antagonists to treat allergy |
| EP0735821A4 (fr) * | 1993-12-21 | 1998-04-01 | Lilly Co Eli | Procedes permettant de traiter ou de prevenir les pathologies associees aux peptides amylo dogenes |
| IL115582A0 (en) * | 1994-10-14 | 1996-01-19 | Lilly Co Eli | Methods for treating resistant tumors |
| WO1996012488A1 (fr) * | 1994-10-20 | 1996-05-02 | Eli Lilly And Company | Antagonistes des recepteurs de bradykinines bicycliques |
| EP0716854A3 (fr) * | 1994-10-20 | 1996-08-28 | Lilly Co Eli | Compositions pour inhiber le récepteur de la neuropeptide Y |
| PT910369E (pt) * | 1996-03-26 | 2010-06-04 | Lilly Co Eli | Benzotiofenos, formulações que os contêm, e métodos |
| US6458811B1 (en) | 1996-03-26 | 2002-10-01 | Eli Lilly And Company | Benzothiophenes formulations containing same and methods |
| CA2206752A1 (fr) | 1996-07-02 | 1998-01-02 | George Joseph Cullinan | Composes de benzothiophene,intermediaires, procedes et methodes d'utilisation |
| US6288105B1 (en) | 1997-04-30 | 2001-09-11 | Eli Lilly And Company | Antithrombotic agents |
| DE69828522T2 (de) | 1997-04-30 | 2005-12-15 | Eli Lilly And Co., Indianapolis | Antithrombotische mittel |
| JP2001522373A (ja) | 1997-04-30 | 2001-11-13 | イーライ・リリー・アンド・カンパニー | 抗血栓剤 |
| CA2287993A1 (fr) | 1997-04-30 | 1998-11-05 | Mary George Johnson | Agents antithrombotiques |
| US6284756B1 (en) | 1998-04-30 | 2001-09-04 | Eli Lilly And Company | Antithrombotic agents |
| DE69904427T2 (de) * | 1998-10-28 | 2003-07-17 | Eli Lilly And Co., Indianapolis | Benzothiophenderivate als antithrombotische Mitteln und Zwischenprodukte |
| US7163949B1 (en) | 1999-11-03 | 2007-01-16 | Amr Technology, Inc. | 4-phenyl substituted tetrahydroisoquinolines and use thereof |
| RU2309953C2 (ru) | 1999-11-03 | 2007-11-10 | Эймр Текнолоджи, Инк. | Арил- и гетероарилзамещенные тетрагидроизохинолины, фармацевтическая композиция и способ лечения на их основе |
| CN100430401C (zh) | 2000-07-11 | 2008-11-05 | Amr科技公司 | 新的4-苯基取代的四氢异喹啉类化合物及其治疗用途 |
| DE60202954T2 (de) | 2001-05-22 | 2006-01-05 | Eli Lilly And Co., Indianapolis | Tetrahydrochinolin-derivate zur behandlung von krankheiten ausgelöst durch zu hohem oder zu niedrigem oestrogenspiegel |
| ATE321754T1 (de) | 2001-05-22 | 2006-04-15 | Lilly Co Eli | 2-substituierte 1,2,3,4-tetrahydrochinoline und derivate davon, zusammensetzungen und verfahren |
| GB0130305D0 (en) * | 2001-12-19 | 2002-02-06 | Amersham Plc | Compounds for imaging alzheimers disease |
| KR101389246B1 (ko) | 2004-07-15 | 2014-04-24 | 브리스톨-마이어스스퀴브컴파니 | 아릴- 및 헤테로아릴-치환된 테트라히드로이소퀴놀린, 및 이것의 노르에피네프린, 도파민 및 세로토닌의 재흡수를 차단하기 위한 용도 |
| US8362075B2 (en) | 2005-05-17 | 2013-01-29 | Merck Sharp & Dohme Corp. | Cyclohexyl sulphones for treatment of cancer |
| UA95454C2 (uk) | 2005-07-15 | 2011-08-10 | Амр Текнолоджи, Інк. | Арил- і гетероарилзаміщені тетрагідробензазепіни і їх застосування для блокування зворотного захоплення норепінефрину, допаміну і серотоніну |
| KR20080048502A (ko) | 2005-09-29 | 2008-06-02 | 머크 앤드 캄파니 인코포레이티드 | 멜라노코르틴-4 수용체 조절제로서의 아실화스피로피페리딘 유도체 |
| GB0603041D0 (en) | 2006-02-15 | 2006-03-29 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
| EP2698157B1 (fr) | 2006-09-22 | 2015-05-20 | Merck Sharp & Dohme Corp. | Procédé de traitement utilisant des inhibiteurs de synthèse d'acide gras |
| US20110218176A1 (en) | 2006-11-01 | 2011-09-08 | Barbara Brooke Jennings-Spring | Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development |
| MX2009007200A (es) | 2007-01-10 | 2009-07-15 | Angeletti P Ist Richerche Bio | Indazoles sustituidos con amida como inhibidores de poli(adp-ribosa)polimerasa (parp). |
| WO2008120653A1 (fr) | 2007-04-02 | 2008-10-09 | Banyu Pharmaceutical Co., Ltd. | Dérivé d'indoledione |
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| CN107090456B (zh) | 2010-08-02 | 2022-01-18 | 瑟纳治疗公司 | 使用短干扰核酸的RNA干扰介导的联蛋白(钙粘蛋白关联蛋白质),β1基因表达的抑制 |
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Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1300575B (de) * | 1965-05-21 | 1969-08-07 | Bristol Myers Co | Benzo[b]thiophene |
| US3975537A (en) * | 1973-09-21 | 1976-08-17 | Smith Kline | Pharmaceutical compositions and methods of producing coronary vasodilation |
| US3880891A (en) * | 1973-09-21 | 1975-04-29 | Smithkline Corp | Substituted benzofurans |
| US3947470A (en) * | 1974-06-20 | 1976-03-30 | Smithkline Corporation | Substituted benzofurans and benzothiophenes |
| US4024273A (en) * | 1974-06-20 | 1977-05-17 | Smithkline Corporation | Coronary vasodilator and anti-anginal compositions comprising substituted benzofurans and benzothiophenes and methods of producing coronary vasodilation and anti-anginal activity |
| US4230862A (en) * | 1975-10-28 | 1980-10-28 | Eli Lilly And Company | Antifertility compounds |
| US4133814A (en) * | 1975-10-28 | 1979-01-09 | Eli Lilly And Company | 2-Phenyl-3-aroylbenzothiophenes useful as antifertility agents |
| US4418068A (en) * | 1981-04-03 | 1983-11-29 | Eli Lilly And Company | Antiestrogenic and antiandrugenic benzothiophenes |
-
1994
- 1994-12-14 WO PCT/US1994/014312 patent/WO1995017382A1/fr not_active Ceased
- 1994-12-14 JP JP7517478A patent/JPH09506898A/ja active Pending
- 1994-12-14 EP EP95904891A patent/EP0736007A4/fr not_active Withdrawn
- 1994-12-14 CA CA002176130A patent/CA2176130A1/fr not_active Abandoned
- 1994-12-14 AU AU13397/95A patent/AU1339795A/en not_active Abandoned
- 1994-12-15 ZA ZA9410040A patent/ZA9410040B/xx unknown
-
1999
- 1999-02-25 MX MXPA99001870A patent/MXPA99001870A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU1339795A (en) | 1995-07-10 |
| EP0736007A4 (fr) | 1997-03-19 |
| EP0736007A1 (fr) | 1996-10-09 |
| ZA9410040B (en) | 1996-06-18 |
| WO1995017382A1 (fr) | 1995-06-29 |
| JPH09506898A (ja) | 1997-07-08 |
| MXPA99001870A (es) | 2004-09-06 |
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