BG64581B1 - Антагонисти на витронектинов рецептор - Google Patents

Info

Publication number

BG64581B1

BG64581B1 BG103299A BG10329999A BG64581B1 BG 64581 B1 BG64581 B1 BG 64581B1 BG 103299 A BG103299 A BG 103299A BG 10329999 A BG10329999 A BG 10329999A BG 64581 B1 BG64581 B1 BG 64581B1

Authority

BG

Bulgaria

Prior art keywords

oxo

tetrahydro

benzazepine

propyloxy

acetic acid

Prior art date

1996-10-02

Links

• Espacenet
• Global Dossier
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• 239000002464 receptor antagonist Substances 0.000 title claims description 5
• 229940044551 receptor antagonist Drugs 0.000 title claims description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 339
• 238000011282 treatment Methods 0.000 claims abstract description 21
• 208000001132 Osteoporosis Diseases 0.000 claims abstract description 10
• 230000033115 angiogenesis Effects 0.000 claims abstract description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 217
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 150
• -1 2-pyridylamino Chemical group 0.000 claims description 138
• 238000000034 method Methods 0.000 claims description 112
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 83
• 238000002360 preparation method Methods 0.000 claims description 76
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 70
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 51
• 229910052786 argon Inorganic materials 0.000 claims description 46
• 239000002253 acid Substances 0.000 claims description 38
• 125000000217 alkyl group Chemical group 0.000 claims description 35
• 229910052739 hydrogen Inorganic materials 0.000 claims description 33
• 125000001318 4-trifluoromethylbenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(F)(F)F 0.000 claims description 20
• 150000003839 salts Chemical class 0.000 claims description 16
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
• 229910052757 nitrogen Inorganic materials 0.000 claims description 13
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 13
• 229910052799 carbon Inorganic materials 0.000 claims description 11
• CMQWVVDFFOCTAU-UHFFFAOYSA-N 2-(5h-2-benzazepin-4-yl)acetic acid Chemical compound C1C(CC(=O)O)=CN=CC2=CC=CC=C21 CMQWVVDFFOCTAU-UHFFFAOYSA-N 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 9
• 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 claims description 8
• WPMAHUIWBYECRS-UHFFFAOYSA-N 2-[8-[3-[(4-aminopyridin-2-yl)amino]propoxy]-3-oxo-1,2,4,5-tetrahydro-2-benzazepin-4-yl]acetic acid Chemical compound NC1=CC=NC(NCCCOC=2C=C3CNC(=O)C(CC(O)=O)CC3=CC=2)=C1 WPMAHUIWBYECRS-UHFFFAOYSA-N 0.000 claims description 7
• 229910052736 halogen Inorganic materials 0.000 claims description 7
• 150000002367 halogens Chemical class 0.000 claims description 7
• 230000002401 inhibitory effect Effects 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 125000006239 protecting group Chemical group 0.000 claims description 6
• TVMGMLXMTPZKMQ-UHFFFAOYSA-N 2-[8-[2-(2-amino-1,3-thiazol-4-yl)ethoxy]-2-methyl-3-oxo-4,5-dihydro-1h-2-benzazepin-4-yl]acetic acid Chemical compound C=1C=C2CC(CC(O)=O)C(=O)N(C)CC2=CC=1OCCC1=CSC(N)=N1 TVMGMLXMTPZKMQ-UHFFFAOYSA-N 0.000 claims description 5
• PPPIHWZZUHYFGB-UHFFFAOYSA-N 2-[8-[2-[6-(methylamino)pyridin-2-yl]ethoxy]-3-oxo-1,2,4,5-tetrahydro-2-benzazepin-4-yl]acetic acid Chemical compound CNC1=CC=CC(CCOC=2C=C3CNC(=O)C(CC(O)=O)CC3=CC=2)=N1 PPPIHWZZUHYFGB-UHFFFAOYSA-N 0.000 claims description 5
• ALBSDNWEUVWZEI-FQEVSTJZSA-N 2-[(4s)-3-oxo-8-[3-(1,4,5,6-tetrahydropyrimidin-2-ylamino)propoxy]-2-[[4-(trifluoromethyl)phenyl]methyl]-4,5-dihydro-1h-2-benzazepin-4-yl]acetic acid Chemical compound C([C@H](C(N(CC=1C=CC(=CC=1)C(F)(F)F)CC1=C2)=O)CC(=O)O)C1=CC=C2OCCCNC1=NCCCN1 ALBSDNWEUVWZEI-FQEVSTJZSA-N 0.000 claims description 4
• KSSPHFGIOASRDE-HNNXBMFYSA-N 2-[(4s)-8-[2-[6-(methylamino)pyridin-2-yl]ethoxy]-3-oxo-2-(2,2,2-trifluoroethyl)-4,5-dihydro-1h-2-benzazepin-4-yl]acetic acid Chemical compound CNC1=CC=CC(CCOC=2C=C3CN(CC(F)(F)F)C(=O)[C@H](CC(O)=O)CC3=CC=2)=N1 KSSPHFGIOASRDE-HNNXBMFYSA-N 0.000 claims description 4
• WPMAHUIWBYECRS-AWEZNQCLSA-N 2-[(4s)-8-[3-[(4-aminopyridin-2-yl)amino]propoxy]-3-oxo-1,2,4,5-tetrahydro-2-benzazepin-4-yl]acetic acid Chemical compound NC1=CC=NC(NCCCOC=2C=C3CNC(=O)[C@H](CC(O)=O)CC3=CC=2)=C1 WPMAHUIWBYECRS-AWEZNQCLSA-N 0.000 claims description 4
• NBZLHCNTIHLZJK-UHFFFAOYSA-N 2-[2-benzyl-3-oxo-8-[3-(pyridin-2-ylamino)propoxy]-4,5-dihydro-1h-2-benzazepin-4-yl]acetic acid Chemical compound C1=C2CN(CC=3C=CC=CC=3)C(=O)C(CC(=O)O)CC2=CC=C1OCCCNC1=CC=CC=N1 NBZLHCNTIHLZJK-UHFFFAOYSA-N 0.000 claims description 4
• PVDGZHKJXXVONO-UHFFFAOYSA-N 2-[3-oxo-8-[3-(pyridin-2-ylamino)propoxy]-2-(2,2,2-trifluoroethyl)-4,5-dihydro-1h-2-benzazepin-4-yl]acetic acid Chemical compound C1=C2CN(CC(F)(F)F)C(=O)C(CC(=O)O)CC2=CC=C1OCCCNC1=CC=CC=N1 PVDGZHKJXXVONO-UHFFFAOYSA-N 0.000 claims description 4
• URDYMLIOCMVKKV-UHFFFAOYSA-N 2-[8-[2-(1h-benzimidazol-2-yl)ethoxy]-3-oxo-1,2,4,5-tetrahydro-2-benzazepin-4-yl]acetic acid Chemical compound C1=C2CNC(=O)C(CC(=O)O)CC2=CC=C1OCCC1=NC2=CC=CC=C2N1 URDYMLIOCMVKKV-UHFFFAOYSA-N 0.000 claims description 4
• JYFKEXVYPPVSLX-UHFFFAOYSA-N 2-[8-[3-[(4-methoxypyridin-2-yl)amino]propoxy]-3-oxo-1,2,4,5-tetrahydro-2-benzazepin-4-yl]acetic acid Chemical compound COC1=CC=NC(NCCCOC=2C=C3CNC(=O)C(CC(O)=O)CC3=CC=2)=C1 JYFKEXVYPPVSLX-UHFFFAOYSA-N 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000000524 functional group Chemical group 0.000 claims description 4
• 230000008569 process Effects 0.000 claims description 4
• ABALEZNMAFLQMF-QHCPKHFHSA-N 2-[(4s)-3-oxo-2-(2-phenylethyl)-8-[3-(pyridin-2-ylamino)propoxy]-4,5-dihydro-1h-2-benzazepin-4-yl]acetic acid Chemical compound C([C@H](C(N(CCC=1C=CC=CC=1)CC1=C2)=O)CC(=O)O)C1=CC=C2OCCCNC1=CC=CC=N1 ABALEZNMAFLQMF-QHCPKHFHSA-N 0.000 claims description 3
• XRRDSVKXZCEJLO-UHFFFAOYSA-N 2-[2-(carboxymethyl)-3-oxo-8-[3-(pyridin-2-ylamino)propoxy]-4,5-dihydro-1h-2-benzazepin-4-yl]acetic acid Chemical compound C1=C2CN(CC(O)=O)C(=O)C(CC(=O)O)CC2=CC=C1OCCCNC1=CC=CC=N1 XRRDSVKXZCEJLO-UHFFFAOYSA-N 0.000 claims description 3
• QPYGAAZQEFGBCP-UHFFFAOYSA-N 2-[2-[(4-aminophenyl)methyl]-3-oxo-8-[3-(pyridin-2-ylamino)propoxy]-4,5-dihydro-1h-2-benzazepin-4-yl]acetic acid Chemical compound C1=CC(N)=CC=C1CN1C(=O)C(CC(O)=O)CC2=CC=C(OCCCNC=3N=CC=CC=3)C=C2C1 QPYGAAZQEFGBCP-UHFFFAOYSA-N 0.000 claims description 3
• QEVFARCJUDGBHM-UHFFFAOYSA-N 2-[2-methyl-3-oxo-8-[3-(pyridin-2-ylamino)propoxy]-4,5-dihydro-1h-2-benzazepin-4-yl]acetic acid Chemical compound C=1C=C2CC(CC(O)=O)C(=O)N(C)CC2=CC=1OCCCNC1=CC=CC=N1 QEVFARCJUDGBHM-UHFFFAOYSA-N 0.000 claims description 3
• JUJDYKKIXFJQKW-UHFFFAOYSA-N 2-[3-oxo-8-[3-(1,4,5,6-tetrahydropyrimidin-2-ylamino)propoxy]-1,2,4,5-tetrahydro-2-benzazepin-4-yl]acetic acid Chemical compound C1=C2CNC(=O)C(CC(=O)O)CC2=CC=C1OCCCNC1=NCCCN1 JUJDYKKIXFJQKW-UHFFFAOYSA-N 0.000 claims description 3
• LGYHUVHIIJSDMP-UHFFFAOYSA-N 2-[3-oxo-8-[3-(pyrimidin-2-ylamino)propoxy]-1,2,4,5-tetrahydro-2-benzazepin-4-yl]acetic acid Chemical compound C1=C2CNC(=O)C(CC(=O)O)CC2=CC=C1OCCCNC1=NC=CC=N1 LGYHUVHIIJSDMP-UHFFFAOYSA-N 0.000 claims description 3
• CBJLRYOFGHMYQK-UHFFFAOYSA-N 2-[8-[3-(1h-imidazol-2-ylamino)propoxy]-3-oxo-1,2,4,5-tetrahydro-2-benzazepin-4-yl]acetic acid Chemical compound C1=C2CNC(=O)C(CC(=O)O)CC2=CC=C1OCCCNC1=NC=CN1 CBJLRYOFGHMYQK-UHFFFAOYSA-N 0.000 claims description 3
• NSMTUKNNHXHRIB-UHFFFAOYSA-N 2-[8-[3-[(4,6-dimethylpyridin-2-yl)amino]propoxy]-2-methyl-3-oxo-4,5-dihydro-1h-2-benzazepin-4-yl]acetic acid Chemical compound C=1C=C2CC(CC(O)=O)C(=O)N(C)CC2=CC=1OCCCNC1=CC(C)=CC(C)=N1 NSMTUKNNHXHRIB-UHFFFAOYSA-N 0.000 claims description 3
• CUDGZLBNJBIXMF-UHFFFAOYSA-N 2-[8-[3-[(4-methylpyridin-2-yl)amino]propoxy]-3-oxo-2-(2,2,2-trifluoroethyl)-4,5-dihydro-1h-2-benzazepin-4-yl]acetic acid Chemical compound CC1=CC=NC(NCCCOC=2C=C3CN(CC(F)(F)F)C(=O)C(CC(O)=O)CC3=CC=2)=C1 CUDGZLBNJBIXMF-UHFFFAOYSA-N 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• VXMWIKKUCXXPPZ-UHFFFAOYSA-N 2-[2-methyl-3-oxo-8-[3-(4,5,6,7-tetrahydro-1h-1,3-diazepin-2-ylamino)propoxy]-4,5-dihydro-1h-2-benzazepin-4-yl]acetic acid Chemical compound C=1C=C2CC(CC(O)=O)C(=O)N(C)CC2=CC=1OCCCNC1=NCCCCN1 VXMWIKKUCXXPPZ-UHFFFAOYSA-N 0.000 claims description 2
• UVDWWBPCVXRCCV-UHFFFAOYSA-N 2-[8-[2-(1h-imidazo[4,5-b]pyridin-2-yl)ethoxy]-3-oxo-1,2,4,5-tetrahydro-2-benzazepin-4-yl]acetic acid Chemical compound C1=C2CNC(=O)C(CC(=O)O)CC2=CC=C1OCCC1=NC2=CC=CN=C2N1 UVDWWBPCVXRCCV-UHFFFAOYSA-N 0.000 claims description 2
• DTUVSXXKDCPWGN-UHFFFAOYSA-N 2-[8-[3-(4,5-dihydro-1h-imidazol-2-ylamino)propoxy]-2-methyl-3-oxo-4,5-dihydro-1h-2-benzazepin-4-yl]acetic acid Chemical compound C=1C=C2CC(CC(O)=O)C(=O)N(C)CC2=CC=1OCCCNC1=NCCN1 DTUVSXXKDCPWGN-UHFFFAOYSA-N 0.000 claims description 2
• ULEFATMVPXFWPZ-UHFFFAOYSA-N 2-[8-[3-[(6-aminopyridin-2-yl)amino]propoxy]-3-oxo-1,2,4,5-tetrahydro-2-benzazepin-4-yl]acetic acid Chemical compound NC1=CC=CC(NCCCOC=2C=C3CNC(=O)C(CC(O)=O)CC3=CC=2)=N1 ULEFATMVPXFWPZ-UHFFFAOYSA-N 0.000 claims description 2
• PQYRYUYLEDLMMP-NRFANRHFSA-N 2-[(4s)-3-oxo-8-[3-(pyridin-2-ylamino)propoxy]-2-[[4-(trifluoromethyl)phenyl]methyl]-4,5-dihydro-1h-2-benzazepin-4-yl]acetic acid Chemical compound C([C@H](C(N(CC=1C=CC(=CC=1)C(F)(F)F)CC1=C2)=O)CC(=O)O)C1=CC=C2OCCCNC1=CC=CC=N1 PQYRYUYLEDLMMP-NRFANRHFSA-N 0.000 claims 1
• CUDGZLBNJBIXMF-KRWDZBQOSA-N 2-[(4s)-8-[3-[(4-methylpyridin-2-yl)amino]propoxy]-3-oxo-2-(2,2,2-trifluoroethyl)-4,5-dihydro-1h-2-benzazepin-4-yl]acetic acid Chemical compound CC1=CC=NC(NCCCOC=2C=C3CN(CC(F)(F)F)C(=O)[C@H](CC(O)=O)CC3=CC=2)=C1 CUDGZLBNJBIXMF-KRWDZBQOSA-N 0.000 claims 1
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