JP2000502704A - ビトロネクチン受容体拮抗物質 - Google Patents
ビトロネクチン受容体拮抗物質Info
- Publication number
- JP2000502704A JP2000502704A JP9524453A JP52445396A JP2000502704A JP 2000502704 A JP2000502704 A JP 2000502704A JP 9524453 A JP9524453 A JP 9524453A JP 52445396 A JP52445396 A JP 52445396A JP 2000502704 A JP2000502704 A JP 2000502704A
- Authority
- JP
- Japan
- Prior art keywords
- amino
- ethyl
- pyridinyl
- compound
- alkyl
- 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.)
- Pending
Links
- 102100022337 Integrin alpha-V Human genes 0.000 title claims abstract description 21
- 108010048673 Vitronectin Receptors Proteins 0.000 title claims abstract description 21
- 239000002464 receptor antagonist Substances 0.000 title abstract description 7
- 229940044551 receptor antagonist Drugs 0.000 title abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 21
- 229910052786 argon Inorganic materials 0.000 claims abstract description 18
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 12
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- 229940122331 Fibrinogen antagonist Drugs 0.000 claims abstract description 8
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 8
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 7
- 125000001475 halogen functional group Chemical group 0.000 claims abstract 4
- 150000001875 compounds Chemical class 0.000 claims description 441
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 243
- 238000002360 preparation method Methods 0.000 claims description 217
- -1 2-pyridinyl Chemical group 0.000 claims description 192
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 149
- 238000000034 method Methods 0.000 claims description 107
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 96
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 60
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 42
- 239000002253 acid Substances 0.000 claims description 42
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 32
- 125000004076 pyridyl group Chemical group 0.000 claims description 31
- 238000004519 manufacturing process Methods 0.000 claims description 29
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 23
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 22
- 229960000583 acetic acid Drugs 0.000 claims description 18
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
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- 108020003175 receptors Proteins 0.000 claims description 13
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 10
- 208000037803 restenosis Diseases 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 8
- 230000005764 inhibitory process Effects 0.000 claims description 8
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 claims description 8
- 206010061218 Inflammation Diseases 0.000 claims description 6
- 241001024304 Mino Species 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- LJOODBDWMQKMFB-UHFFFAOYSA-N cyclohexylacetic acid Chemical compound OC(=O)CC1CCCCC1 LJOODBDWMQKMFB-UHFFFAOYSA-N 0.000 claims description 6
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- 125000006239 protecting group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- HHGJSOAYVHZIMK-UHFFFAOYSA-N 2-butoxy-2-phenylpropanoic acid Chemical compound CCCCOC(C)(C(O)=O)C1=CC=CC=C1 HHGJSOAYVHZIMK-UHFFFAOYSA-N 0.000 claims description 2
- 230000033115 angiogenesis Effects 0.000 claims description 2
- QQMDYJFMRYWZKP-UHFFFAOYSA-N 2-[1-hydroxy-4-[4-[3-(pyridin-2-ylamino)propyl]piperazin-1-yl]cyclohexyl]acetic acid Chemical compound C1CC(CC(=O)O)(O)CCC1N1CCN(CCCNC=2N=CC=CC=2)CC1 QQMDYJFMRYWZKP-UHFFFAOYSA-N 0.000 claims 1
- ZYLASKWUHMGCCM-UHFFFAOYSA-N 2-[6-[2-(pyridin-2-ylamino)ethylcarbamoyl]-3,4-dihydro-1h-isoquinolin-2-yl]acetic acid Chemical compound C=1C=C2CN(CC(=O)O)CCC2=CC=1C(=O)NCCNC1=CC=CC=N1 ZYLASKWUHMGCCM-UHFFFAOYSA-N 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 230000008485 antagonism Effects 0.000 claims 1
- 125000000524 functional group Chemical group 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 claims 1
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- 229910002091 carbon monoxide Inorganic materials 0.000 abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 132
- 239000000243 solution Substances 0.000 description 127
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- 238000006243 chemical reaction Methods 0.000 description 113
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 102
- 239000000203 mixture Substances 0.000 description 91
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- 239000012141 concentrate Substances 0.000 description 70
- 235000008504 concentrate Nutrition 0.000 description 69
- 239000000741 silica gel Substances 0.000 description 67
- 229910002027 silica gel Inorganic materials 0.000 description 67
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 64
- 235000019439 ethyl acetate Nutrition 0.000 description 57
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 56
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 54
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 50
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 43
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 43
- 238000003756 stirring Methods 0.000 description 42
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 40
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 39
- 229910052763 palladium Inorganic materials 0.000 description 37
- 238000004587 chromatography analysis Methods 0.000 description 34
- 239000012044 organic layer Substances 0.000 description 33
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 33
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 30
- 108010012088 Fibrinogen Receptors Proteins 0.000 description 26
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 26
- 239000007787 solid Substances 0.000 description 26
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- 239000011734 sodium Substances 0.000 description 24
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- 239000000284 extract Substances 0.000 description 23
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- 239000010410 layer Substances 0.000 description 21
- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 20
- 239000005557 antagonist Substances 0.000 description 20
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 20
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 19
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- TYHXIJJQIJKFSO-UHFFFAOYSA-N n'-pyridin-2-ylethane-1,2-diamine Chemical compound NCCNC1=CC=CC=N1 TYHXIJJQIJKFSO-UHFFFAOYSA-N 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
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- 239000002319 fibrinogen receptor antagonist Substances 0.000 description 14
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- 239000000126 substance Substances 0.000 description 14
- IDWUSJOEYZAKSW-UHFFFAOYSA-N 3-(pyridin-1-ium-2-ylamino)propanoate Chemical compound OC(=O)CCNC1=CC=CC=N1 IDWUSJOEYZAKSW-UHFFFAOYSA-N 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
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- 238000000921 elemental analysis Methods 0.000 description 12
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- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 12
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- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
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- BDUZNKOFYSWAOZ-UHFFFAOYSA-N tert-butyl n-[2-(4-hydroxyphenyl)-2-oxoethyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)CC(=O)C1=CC=C(O)C=C1 BDUZNKOFYSWAOZ-UHFFFAOYSA-N 0.000 description 1
- HEXGKBKMDDSFRI-UHFFFAOYSA-N tert-butyl n-methyl-n-[2-(pyridin-2-ylamino)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)N(C)CCNC1=CC=CC=N1 HEXGKBKMDDSFRI-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pyridine Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US936795P | 1995-12-29 | 1995-12-29 | |
| US60/009,367 | 1995-12-29 | ||
| PCT/US1996/020327 WO1997024124A1 (en) | 1995-12-29 | 1996-12-20 | Vitronectin receptor antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2000502704A true JP2000502704A (ja) | 2000-03-07 |
Family
ID=21737218
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9524453A Pending JP2000502704A (ja) | 1995-12-29 | 1996-12-20 | ビトロネクチン受容体拮抗物質 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US6159964A (enExample) |
| EP (1) | EP0906103A1 (enExample) |
| JP (1) | JP2000502704A (enExample) |
| KR (1) | KR19990076877A (enExample) |
| CN (1) | CN1209063A (enExample) |
| AU (1) | AU1295597A (enExample) |
| BR (1) | BR9612381A (enExample) |
| CZ (1) | CZ203898A3 (enExample) |
| IL (1) | IL125030A0 (enExample) |
| NO (1) | NO983001L (enExample) |
| PL (1) | PL327626A1 (enExample) |
| TR (1) | TR199801254T2 (enExample) |
| WO (1) | WO1997024124A1 (enExample) |
| ZA (1) | ZA9610854B (enExample) |
Families Citing this family (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0777657A1 (en) * | 1994-08-22 | 1997-06-11 | Smithkline Beecham Corporation | Bicyclic compounds |
| KR19990076876A (ko) * | 1995-12-29 | 1999-10-25 | 스티븐 베네티아너 | 비트로넥틴 수용체 길항제 |
| WO1997037655A1 (en) * | 1996-04-10 | 1997-10-16 | Merck & Co., Inc. | αvβ3 ANTAGONISTS |
| US20030125317A1 (en) | 1996-10-02 | 2003-07-03 | Smithkline Beecham Corporation | Vitronectin receptor antagonists |
| US6482821B2 (en) | 1996-12-20 | 2002-11-19 | Hoechst Aktiengellschaft | Vitronectin receptor antagonists, their preparation and their use |
| DE19653647A1 (de) | 1996-12-20 | 1998-06-25 | Hoechst Ag | Vitronectin - Rezeptorantagonisten, deren Herstellung sowie deren Verwendung |
| DE19653645A1 (de) * | 1996-12-20 | 1998-06-25 | Hoechst Ag | Vitronectin - Rezeptorantagonisten, deren Herstellung sowie deren Verwendung |
| US6218387B1 (en) | 1996-12-20 | 2001-04-17 | Hoechst Aktiengesellschaft | Vitronectin receptor anatagonists, their preparation and their use |
| CO4920232A1 (es) * | 1997-01-08 | 2000-05-29 | Smithkline Beecham Corp | Acidos aceticos dibenzo [a,d] cicloheptano con actividad antagonista del receptor de vitronectin |
| EP1000031A4 (en) * | 1997-07-25 | 2001-08-16 | Smithkline Beecham Corp | VITRONECTIN RECEPTOR ANTAGONISTS |
| EP1047425A4 (en) * | 1997-12-17 | 2009-04-22 | Merck & Co Inc | INTEGRIN RECEPTOR ANTAGONISTS |
| ES2226413T3 (es) | 1998-02-26 | 2005-03-16 | Celltech Therapeutics Limited | Derivados de fenilalanina como inhibidores de alfa-4 integrinas. |
| WO1999045927A1 (en) * | 1998-03-10 | 1999-09-16 | Smithkline Beecham Corporation | Vitronectin receptor antagonists |
| GB9805655D0 (en) | 1998-03-16 | 1998-05-13 | Celltech Therapeutics Ltd | Chemical compounds |
| US6521626B1 (en) | 1998-03-24 | 2003-02-18 | Celltech R&D Limited | Thiocarboxamide derivatives |
| GB9811969D0 (en) | 1998-06-03 | 1998-07-29 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9812088D0 (en) | 1998-06-05 | 1998-08-05 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9814414D0 (en) | 1998-07-03 | 1998-09-02 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9821061D0 (en) | 1998-09-28 | 1998-11-18 | Celltech Therapeutics Ltd | Chemical compounds |
| SE9803773D0 (sv) * | 1998-11-05 | 1998-11-05 | Astra Pharma Prod | Compounds |
| GB9826174D0 (en) | 1998-11-30 | 1999-01-20 | Celltech Therapeutics Ltd | Chemical compounds |
| AU747503B2 (en) | 1999-02-03 | 2002-05-16 | Merck & Co., Inc. | Benzazepine derivatives as alpha-V integrin receptor antagonists |
| CA2371824A1 (en) | 1999-02-20 | 2000-08-24 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | .beta.-alanine derivatives |
| US6518283B1 (en) | 1999-05-28 | 2003-02-11 | Celltech R&D Limited | Squaric acid derivatives |
| CA2378860A1 (en) | 1999-07-21 | 2001-02-01 | American Home Products Corporation | Bicyclic antagonists selective for the .alpha.v.beta.3 integrin |
| DE19939980A1 (de) | 1999-08-24 | 2001-03-01 | Merck Patent Gmbh | Inhibitoren des Integrins alphavbeta¶3¶ |
| US6534513B1 (en) | 1999-09-29 | 2003-03-18 | Celltech R&D Limited | Phenylalkanoic acid derivatives |
| DE10028575A1 (de) | 2000-06-14 | 2002-03-14 | Basf Ag | Integrinliganden |
| GB9929988D0 (en) * | 1999-12-17 | 2000-02-09 | Celltech Therapeutics Ltd | Chemical compounds |
| US6455539B2 (en) | 1999-12-23 | 2002-09-24 | Celltech R&D Limited | Squaric acid derivates |
| DE60130910T2 (de) | 2000-04-17 | 2008-07-10 | Ucb Pharma, S.A. | Enamin-derivate als zell-adhäsionsmoleküle |
| US6403608B1 (en) | 2000-05-30 | 2002-06-11 | Celltech R&D, Ltd. | 3-Substituted isoquinolin-1-yl derivatives |
| US6545013B2 (en) | 2000-05-30 | 2003-04-08 | Celltech R&D Limited | 2,7-naphthyridine derivatives |
| DE10028402A1 (de) * | 2000-06-13 | 2001-12-20 | Merck Patent Gmbh | Pyridin-2-yl-aminoalkycarbonylglycyl-beta-alanin und Derivate |
| US6740654B2 (en) | 2000-07-07 | 2004-05-25 | Celltech R & D Limited | Squaric acid derivatives |
| AU2001275724A1 (en) | 2000-08-02 | 2002-02-13 | Celltech R&D Limited | 3-substituted isoquinolin-1-yl derivatives |
| AU2001288485A1 (en) * | 2000-08-29 | 2002-03-13 | Balekudru Devadas | Compounds containing a bicyclic ring system useful as alpha v beta 3 antagonists |
| EP1313705A1 (en) * | 2000-08-30 | 2003-05-28 | Pharmacia Corporation | Gem-substituted alpha v beta 3 integrin antagonists |
| US6531494B1 (en) | 2001-08-29 | 2003-03-11 | Pharmacia Corporation | Gem-substituted αvβ3 antagonists |
| US6472372B1 (en) * | 2000-12-06 | 2002-10-29 | Ortho-Mcneil Pharmaceuticals, Inc. | 6-O-Carbamoyl ketolide antibacterials |
| KR100376088B1 (ko) * | 2001-03-09 | 2003-03-28 | 주식회사 태평양 | 3-아미노프로필코질포스페이트 및 그의 염을 함유한미백화장료 조성물 |
| EP1381384B1 (en) | 2001-04-24 | 2011-05-25 | Merck Patent GmbH | COMBINATION THERAPY USING ANTI-ANGIOGENIC AGENTS AND TNFalpha |
| KR20040058229A (ko) | 2001-10-22 | 2004-07-03 | 더 스크립스 리서치 인스티튜트 | 항체 표적화 화합물 |
| CA2469304A1 (en) | 2001-12-05 | 2003-06-19 | Ortho-Mcneil Pharmaceutical, Inc. | 6-o acyl ketolide antibacterials |
| GB0130341D0 (en) * | 2001-12-19 | 2002-02-06 | Smithkline Beecham Plc | Compounds |
| ES2333724T3 (es) | 2003-09-26 | 2010-02-26 | Merck Serono Sa | Secuencias lideres para uso en la produccion de proteinas. |
| UA87854C2 (en) | 2004-06-07 | 2009-08-25 | Мерк Энд Ко., Инк. | N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators |
| US20070122408A1 (en) * | 2005-10-20 | 2007-05-31 | The Scripps Research Institute | Fc Labeling for Immunostaining and Immunotargeting |
| CA2635580A1 (en) * | 2005-12-30 | 2007-07-12 | Alantos Pharmaceuticals Holding, Inc. | Substituted bis-amide metalloprotease inhibitors |
| EP1973569B1 (en) | 2006-01-18 | 2013-05-22 | Merck Patent GmbH | Specific therapy using integrin ligands for treating cancer |
| JP2010516645A (ja) | 2007-01-18 | 2010-05-20 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | 癌を治療するためのインテグリンリガンドを用いる特異的療法および薬剤 |
| DE102007038250A1 (de) * | 2007-08-13 | 2009-02-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neues Herstellverfahren |
| JP5637855B2 (ja) | 2007-11-08 | 2014-12-10 | ザ ジェネラル ホスピタル コーポレイション | 蛋白尿症の治療のための方法及び組成物 |
| PT2222636E (pt) | 2007-12-21 | 2013-07-16 | Ligand Pharm Inc | Moduladores seletivos de recetores de andrógeno (sarms) e suas utilizações |
| US8518927B2 (en) | 2009-02-10 | 2013-08-27 | The Scripps Research Institute | Chemically programmed vaccination |
| CN102459249A (zh) | 2009-05-22 | 2012-05-16 | 埃克塞里艾克西斯公司 | 作为PI3K/mTOR抑制剂的苯并氧氮杂环庚三烯以及它们使用与制造方法 |
| US20120130146A1 (en) | 2009-05-25 | 2012-05-24 | Merck Patent Gmbh | Continuous administration of cilengitide in cancer treatments |
| ES2864079T3 (es) | 2014-05-30 | 2021-10-13 | Pfizer | Derivados de carbonitrilo como moduladores selectivos del receptor de andrógenos |
| MX389591B (es) | 2014-08-29 | 2025-03-20 | Tes Pharma S R L | INHIBIDORES DE ACIDO A-AMINO-ß-CARBOXIMUCONICO SEMIALDEHIDO DESCARBOXILASA |
| ES2993451T3 (en) | 2016-06-13 | 2024-12-30 | Glaxosmithkline Ip Dev Ltd | Substituted pyridines as inhibitors of dnmt1 |
| IL316954A (en) * | 2017-02-28 | 2025-01-01 | Morphic Therapeutic Inc | (Alpha-V)(beta-6)integrin inhibitors |
| EP3760202A1 (en) | 2017-02-28 | 2021-01-06 | Morphic Therapeutic, Inc. | Inhibitors of (alpha-v)(beta-6) integrin |
| CN108558836A (zh) * | 2018-05-14 | 2018-09-21 | 东南大学 | 一类具有双重作用机制的dpp-4抑制剂及其用途 |
| WO2020047208A1 (en) | 2018-08-29 | 2020-03-05 | Morphic Therapeutic, Inc. | Inhibitors of (alpha-v)(beta-6) integrin |
| UY38353A (es) | 2018-08-29 | 2020-03-31 | Morphic Therapeutic Inc | Inhibición de integrina alfavbeta6 |
| UY38352A (es) | 2018-08-29 | 2020-03-31 | Morphic Therapeutic Inc | Inhibidores de integrina alfavbeta6 |
| MX2021012690A (es) | 2019-04-19 | 2022-01-31 | Ligand Pharm Inc | Formas cristalinas y metodos para producir formas cristalinas de un compuesto. |
| WO2023275715A1 (en) | 2021-06-30 | 2023-01-05 | Pfizer Inc. | Metabolites of selective androgen receptor modulators |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3450707A (en) * | 1966-12-13 | 1969-06-17 | Sterling Drug Inc | Certain 2-anilino-pyridine derivatives |
| US3627754A (en) * | 1970-05-13 | 1971-12-14 | Hoffmann La Roche | Process for preparing 7-lower alkanoyl benzodiazepines utilizing ceric salts |
| NZ259802A (en) * | 1992-12-21 | 1997-10-24 | Smithkline Beecham Corp | Bicyclic derivatives and pharmaceutical compositions |
| EP0762882A4 (en) * | 1994-06-29 | 2002-09-11 | Smithkline Beecham Corp | Vibronectin Receptor Antagonists |
| ZA9610853B (en) * | 1995-12-29 | 1998-04-06 | Smithkline Beecham Corp | Processes and intermediates for preparing pharmaceuticals. |
-
1996
- 1996-12-20 AU AU12955/97A patent/AU1295597A/en not_active Abandoned
- 1996-12-20 US US09/091,937 patent/US6159964A/en not_active Expired - Fee Related
- 1996-12-20 KR KR1019980705004A patent/KR19990076877A/ko not_active Withdrawn
- 1996-12-20 IL IL12503096A patent/IL125030A0/xx unknown
- 1996-12-20 CZ CZ982038A patent/CZ203898A3/cs unknown
- 1996-12-20 PL PL96327626A patent/PL327626A1/xx unknown
- 1996-12-20 CN CN96180114A patent/CN1209063A/zh active Pending
- 1996-12-20 EP EP96943818A patent/EP0906103A1/en not_active Withdrawn
- 1996-12-20 TR TR1998/01254T patent/TR199801254T2/xx unknown
- 1996-12-20 JP JP9524453A patent/JP2000502704A/ja active Pending
- 1996-12-20 BR BR9612381A patent/BR9612381A/pt unknown
- 1996-12-20 WO PCT/US1996/020327 patent/WO1997024124A1/en not_active Ceased
- 1996-12-23 ZA ZA9610854A patent/ZA9610854B/xx unknown
-
1998
- 1998-06-26 NO NO983001A patent/NO983001L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0906103A4 (enExample) | 1999-04-07 |
| EP0906103A1 (en) | 1999-04-07 |
| PL327626A1 (en) | 1998-12-21 |
| NO983001D0 (no) | 1998-06-26 |
| WO1997024124A1 (en) | 1997-07-10 |
| US6159964A (en) | 2000-12-12 |
| ZA9610854B (en) | 1998-04-02 |
| CN1209063A (zh) | 1999-02-24 |
| TR199801254T2 (xx) | 1998-10-21 |
| IL125030A0 (en) | 1999-01-26 |
| KR19990076877A (ko) | 1999-10-25 |
| AU1295597A (en) | 1997-07-28 |
| BR9612381A (pt) | 1999-07-13 |
| NO983001L (no) | 1998-08-26 |
| CZ203898A3 (cs) | 1999-03-17 |
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