CA2241724A1 - Vitronectin receptor antagonists - Google Patents
Vitronectin receptor antagonists Download PDFInfo
- Publication number
- CA2241724A1 CA2241724A1 CA002241724A CA2241724A CA2241724A1 CA 2241724 A1 CA2241724 A1 CA 2241724A1 CA 002241724 A CA002241724 A CA 002241724A CA 2241724 A CA2241724 A CA 2241724A CA 2241724 A1 CA2241724 A1 CA 2241724A1
- Authority
- CA
- Canada
- Prior art keywords
- amino
- methyl
- pyridinyl
- acid
- compound
- 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
- 102100022337 Integrin alpha-V Human genes 0.000 title claims abstract description 24
- 108010048673 Vitronectin Receptors Proteins 0.000 title claims abstract description 24
- 239000002464 receptor antagonist Substances 0.000 title abstract description 7
- 229940044551 receptor antagonist Drugs 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 333
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims description 129
- -1 7-aminocarbonyl-2,3,4,5-tetrahydro-3-oxo-methyl-1H-1-benzazepine-2-acetic acid Chemical compound 0.000 claims description 125
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 77
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 70
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 70
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 59
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 58
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 39
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 19
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 13
- 230000002378 acidificating effect Effects 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 229940122331 Fibrinogen antagonist Drugs 0.000 claims description 10
- 208000037803 restenosis Diseases 0.000 claims description 10
- 201000001320 Atherosclerosis Diseases 0.000 claims description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 claims description 8
- 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 claims description 8
- 201000011510 cancer Diseases 0.000 claims description 8
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 230000005764 inhibitory process Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 235000019260 propionic acid Nutrition 0.000 claims description 5
- 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 5
- 229910052786 argon Inorganic materials 0.000 claims description 4
- 150000004702 methyl esters Chemical class 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
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000005647 linker group Chemical group 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 125000002233 tyrosyl group Chemical group 0.000 claims description 3
- PZLAVGLCLIXFGV-UHFFFAOYSA-N 2-(1-acetyl-7-carbamoyl-4-methyl-3-oxo-2,5-dihydro-1,4-benzodiazepin-2-yl)acetic acid Chemical compound CC(=O)N1C(CC(O)=O)C(=O)N(C)CC2=CC(C(N)=O)=CC=C21 PZLAVGLCLIXFGV-UHFFFAOYSA-N 0.000 claims description 2
- ZKACMSMSOKLASA-UHFFFAOYSA-N 2-(7-carbamoyl-4-methyl-3-oxo-2,5-dihydro-1h-1,4-benzodiazepin-2-yl)acetic acid Chemical compound N1C(CC(O)=O)C(=O)N(C)CC2=CC(C(N)=O)=CC=C21 ZKACMSMSOKLASA-UHFFFAOYSA-N 0.000 claims description 2
- KFGMFNQDUCGULF-UHFFFAOYSA-N 2-[4-[2-[(6-aminopyridin-2-yl)methyl-methylamino]acetyl]phenoxy]acetic acid Chemical compound C=1C=CC(N)=NC=1CN(C)CC(=O)C1=CC=C(OCC(O)=O)C=C1 KFGMFNQDUCGULF-UHFFFAOYSA-N 0.000 claims description 2
- RPCJMFOLTVUOAU-UHFFFAOYSA-N 2-[4-[2-[[3-(6-aminopyridin-2-yl)-2-oxopropyl]amino]acetyl]phenoxy]acetic acid Chemical compound NC1=CC=CC(CC(=O)CNCC(=O)C=2C=CC(OCC(O)=O)=CC=2)=N1 RPCJMFOLTVUOAU-UHFFFAOYSA-N 0.000 claims description 2
- 230000033115 angiogenesis Effects 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 5
- ZDOGVSPSZFGVPC-IBGZPJMESA-N (2s)-3-[4-[3-(6-aminopyridin-2-yl)propoxy]phenyl]-2-(butylsulfonylamino)propanoic acid Chemical compound C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1OCCCC1=CC=CC(N)=N1 ZDOGVSPSZFGVPC-IBGZPJMESA-N 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- JNKHWOLOCTZQRZ-HNNXBMFYSA-N 2-[(2s)-7-[(6-aminopyridin-2-yl)methylcarbamoyl]-4-methyl-3-oxo-2,5-dihydro-1h-1,4-benzodiazepin-2-yl]acetic acid Chemical compound O=C([C@H](CC(O)=O)NC1=CC=2)N(C)CC1=CC=2C(=O)NCC1=CC=CC(N)=N1 JNKHWOLOCTZQRZ-HNNXBMFYSA-N 0.000 claims 1
- FPJWMYIEBRJFFY-KRWDZBQOSA-N 2-[(2s)-7-[[6-(ethylamino)pyridin-2-yl]methylcarbamoyl]-4-methyl-3-oxo-2,5-dihydro-1h-1,4-benzodiazepin-2-yl]acetic acid Chemical compound CCNC1=CC=CC(CNC(=O)C=2C=C3CN(C)C(=O)[C@H](CC(O)=O)NC3=CC=2)=N1 FPJWMYIEBRJFFY-KRWDZBQOSA-N 0.000 claims 1
- QRJPCCAPACNTNO-UHFFFAOYSA-N 2-[4-[2-[(6-aminopyridin-2-yl)methyl-methylamino]acetyl]-2-(carboxymethoxy)phenoxy]acetic acid Chemical compound C=1C=CC(N)=NC=1CN(C)CC(=O)C1=CC=C(OCC(O)=O)C(OCC(O)=O)=C1 QRJPCCAPACNTNO-UHFFFAOYSA-N 0.000 claims 1
- WTYBIMVNJPQSCU-UHFFFAOYSA-N 2-[4-[2-[[3-(6-aminopyridin-2-yl)-2-oxopropyl]amino]acetyl]-2-(carboxymethoxy)phenoxy]acetic acid Chemical compound NC1=CC=CC(CC(=O)CNCC(=O)C=2C=C(OCC(O)=O)C(OCC(O)=O)=CC=2)=N1 WTYBIMVNJPQSCU-UHFFFAOYSA-N 0.000 claims 1
- OAPIZQNCJBCONN-UHFFFAOYSA-N 2-[4-[4-[(6-aminopyridin-2-yl)methyl]piperazin-1-yl]-1-hydroxycyclohexyl]acetic acid Chemical compound NC1=CC=CC(CN2CCN(CC2)C2CCC(O)(CC(O)=O)CC2)=N1 OAPIZQNCJBCONN-UHFFFAOYSA-N 0.000 claims 1
- IXVRELRINKYYHA-UHFFFAOYSA-N 2-[4-[4-[(6-aminopyridin-2-yl)methyl]piperazin-1-yl]piperidin-1-yl]acetic acid Chemical compound NC1=CC=CC(CN2CCN(CC2)C2CCN(CC(O)=O)CC2)=N1 IXVRELRINKYYHA-UHFFFAOYSA-N 0.000 claims 1
- MLFXQJYCHHQRAQ-UHFFFAOYSA-N 2-[4-[4-[2-(6-aminopyridin-2-yl)ethyl]piperazin-1-yl]-1-hydroxycyclohexyl]acetic acid Chemical compound NC1=CC=CC(CCN2CCN(CC2)C2CCC(O)(CC(O)=O)CC2)=N1 MLFXQJYCHHQRAQ-UHFFFAOYSA-N 0.000 claims 1
- GIHQMXGZSLFOEB-UHFFFAOYSA-N 2-[6-[(6-aminopyridin-2-yl)methyl-methylcarbamoyl]-1-oxo-3,4-dihydroisoquinolin-2-yl]acetic acid Chemical compound C=1C=C2C(=O)N(CC(O)=O)CCC2=CC=1C(=O)N(C)CC1=CC=CC(N)=N1 GIHQMXGZSLFOEB-UHFFFAOYSA-N 0.000 claims 1
- NMIODDRCNNRUAU-UHFFFAOYSA-N 2-[6-[(6-aminopyridin-2-yl)methyl-methylcarbamoyl]-3,4-dihydro-1h-isoquinolin-2-yl]acetic acid Chemical compound C=1C=C2CN(CC(O)=O)CCC2=CC=1C(=O)N(C)CC1=CC=CC(N)=N1 NMIODDRCNNRUAU-UHFFFAOYSA-N 0.000 claims 1
- POJYSBCTCAMFHK-UHFFFAOYSA-N 3-[4-[1-[(6-aminopyridin-2-yl)methyl]-3-methoxy-5-oxo-2h-pyrrol-4-yl]phenyl]propanoic acid Chemical compound C1C(OC)=C(C=2C=CC(CCC(O)=O)=CC=2)C(=O)N1CC1=CC=CC(N)=N1 POJYSBCTCAMFHK-UHFFFAOYSA-N 0.000 claims 1
- MIFOPPGYFRUQQF-UHFFFAOYSA-N 3-[[2-[3-[2-(6-aminopyridin-2-yl)ethyl]-4,5-dihydro-1,2-oxazol-5-yl]acetyl]amino]butanoic acid Chemical compound O1C(CC(=O)NC(CC(O)=O)C)CC(CCC=2N=C(N)C=CC=2)=N1 MIFOPPGYFRUQQF-UHFFFAOYSA-N 0.000 claims 1
- SUKZQZBGLRQKIV-STQMWFEESA-N CCC(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 Chemical compound CCC(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SUKZQZBGLRQKIV-STQMWFEESA-N 0.000 claims 1
- 206010061218 Inflammation Diseases 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 230000008485 antagonism Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000000524 functional group Chemical group 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 120
- 239000000243 solution Substances 0.000 description 110
- 229910001868 water Inorganic materials 0.000 description 100
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 96
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 82
- 238000002360 preparation method Methods 0.000 description 77
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 71
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 65
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 53
- 239000000203 mixture Substances 0.000 description 50
- 239000000741 silica gel Substances 0.000 description 48
- 229910002027 silica gel Inorganic materials 0.000 description 48
- 235000019439 ethyl acetate Nutrition 0.000 description 45
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 44
- 239000002253 acid Substances 0.000 description 37
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 35
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
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- 238000004587 chromatography analysis Methods 0.000 description 30
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- 238000006243 chemical reaction Methods 0.000 description 28
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
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- 210000004027 cell Anatomy 0.000 description 26
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 26
- 108010012088 Fibrinogen Receptors Proteins 0.000 description 25
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 25
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
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- 239000003921 oil Substances 0.000 description 23
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- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 21
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 21
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 20
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 17
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- 239000002904 solvent Substances 0.000 description 16
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- 230000024279 bone resorption Effects 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
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- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical class [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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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
- C07D213/73—Unsubstituted amino or imino radicals
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- C—CHEMISTRY; METALLURGY
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- 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
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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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
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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
- C07D401/10—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 carbon chain containing aromatic rings
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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
- 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
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US953295P | 1995-12-29 | 1995-12-29 | |
| US60/009,532 | 1995-12-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2241724A1 true CA2241724A1 (en) | 1997-07-10 |
Family
ID=21738237
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002241724A Abandoned CA2241724A1 (en) | 1995-12-29 | 1996-12-20 | Vitronectin receptor antagonists |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP0895475A4 (cs) |
| JP (1) | JP2000502708A (cs) |
| KR (1) | KR19990076876A (cs) |
| CN (1) | CN1209060A (cs) |
| AU (1) | AU1353897A (cs) |
| BR (1) | BR9612378A (cs) |
| CA (1) | CA2241724A1 (cs) |
| CZ (1) | CZ203798A3 (cs) |
| HU (1) | HUP9901116A2 (cs) |
| IL (1) | IL125034A0 (cs) |
| MX (1) | MX9805253A (cs) |
| NO (1) | NO983002L (cs) |
| PL (1) | PL327919A1 (cs) |
| TR (1) | TR199801255T2 (cs) |
| WO (1) | WO1997024122A1 (cs) |
| ZA (1) | ZA9610855B (cs) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0777657A1 (en) * | 1994-08-22 | 1997-06-11 | Smithkline Beecham Corporation | Bicyclic compounds |
| JP2000516197A (ja) * | 1996-01-16 | 2000-12-05 | メルク エンド カンパニー インコーポレーテッド | インテグリンレセプターアンタゴニスト |
| ATE227268T1 (de) * | 1996-04-10 | 2002-11-15 | Merck & Co Inc | Alpha v beta 3 antagonisten |
| US20030125317A1 (en) | 1996-10-02 | 2003-07-03 | Smithkline Beecham Corporation | Vitronectin receptor antagonists |
| US6218387B1 (en) | 1996-12-20 | 2001-04-17 | Hoechst Aktiengesellschaft | Vitronectin receptor anatagonists, their preparation and their use |
| US6482821B2 (en) | 1996-12-20 | 2002-11-19 | Hoechst Aktiengellschaft | Vitronectin receptor antagonists, their preparation and their use |
| DE19653645A1 (de) * | 1996-12-20 | 1998-06-25 | Hoechst Ag | Vitronectin - Rezeptorantagonisten, deren Herstellung sowie deren Verwendung |
| DE19653647A1 (de) | 1996-12-20 | 1998-06-25 | Hoechst Ag | Vitronectin - Rezeptorantagonisten, deren Herstellung sowie deren Verwendung |
| 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 |
| AR015241A1 (es) * | 1998-03-10 | 2001-04-18 | Smithkline Beecham Corp | Antagonistas del receptor de vitronectina composicion farmaceutica que los contiene, procedimiento para su preparacion y su empleo para la fabricacion deun medicamento. |
| CN1172930C (zh) * | 1998-04-01 | 2004-10-27 | 詹森药业有限公司 | 抑制pdeiv之吡啶衍生物类 |
| GB9812088D0 (en) * | 1998-06-05 | 1998-08-05 | Celltech Therapeutics Ltd | Chemical compounds |
| US7045519B2 (en) | 1998-06-19 | 2006-05-16 | Chiron Corporation | Inhibitors of glycogen synthase kinase 3 |
| SE9803518D0 (sv) * | 1998-10-15 | 1998-10-15 | Astra Pharma Prod | Novel compounds |
| CA2358855A1 (en) | 1999-02-03 | 2000-08-10 | Merck & Co., Inc. | Benzazepine derivatives as alpha-v integrin receptor antagonists |
| US6723711B2 (en) * | 1999-05-07 | 2004-04-20 | Texas Biotechnology Corporation | Propanoic acid derivatives that inhibit the binding of integrins to their receptors |
| CN1374863A (zh) | 1999-07-21 | 2002-10-16 | 惠氏公司 | αvβ3整联蛋白的双环选择性拮抗剂 |
| EG24179A (en) * | 1999-09-07 | 2008-09-28 | Smithkline Beecham Corp | Vitronectin receptor antagonists |
| DE10028575A1 (de) | 2000-06-14 | 2002-03-14 | Basf Ag | Integrinliganden |
| FR2800067B1 (fr) * | 1999-10-21 | 2004-12-17 | Rhodia Chimie Sa | Intermediaires de fabrication d'un derive de type benzofurane ou benzothiophene nitre en position 5 et leurs utilisations |
| FR2820743B1 (fr) | 2001-02-09 | 2005-02-25 | Pf Medicament | Procede et intermediaires de synthese pour la preparation de derives de pyridin-2-yl-methylamine |
| HUP0303927A3 (en) | 2001-04-24 | 2006-03-28 | Merck Patent Gmbh | Combination therapy using anti-angiogenic agents and tnf-alpha |
| WO2005039506A2 (en) * | 2003-10-24 | 2005-05-06 | Exelixis, Inc. | P70s6 kinase modulators and method of use |
| NZ588139A (en) | 2004-04-08 | 2012-02-24 | Targegen Inc | 7-Aryl-3-arylamino-benzo[1,2,4]triazine derivatives |
| UA87854C2 (en) | 2004-06-07 | 2009-08-25 | Мерк Энд Ко., Инк. | N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators |
| WO2006041046A1 (ja) * | 2004-10-13 | 2006-04-20 | Sankyo Company, Limited | ピリジン誘導体 |
| WO2006115652A1 (en) | 2005-04-20 | 2006-11-02 | Janssen Pharmaceutica, N.V. | Fluorinated pyridine n-oxide thrombin modulators and process for n-oxidation of nitrogen containing heteroaryls |
| BR122021011787B1 (pt) | 2005-11-01 | 2022-01-25 | Impact Biomedicines, Inc | Inibidores de biaril meta pirimidina de cinases, composição farmacêutica e processo para preparar uma composição farmacêutica |
| JP2009523813A (ja) | 2006-01-18 | 2009-06-25 | 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 | 癌を治療するためにインテグリンのリガンドを使用する特異的な治療法 |
| TW200811164A (en) * | 2006-05-12 | 2008-03-01 | Jerini Ag | New heterocyclic compounds for the inhibition of integrins and use thereof |
| EP2101805B1 (en) | 2007-01-18 | 2012-11-07 | Merck Patent GmbH | Integrin ligands for use in treating cancer |
| ES2457822T3 (es) | 2007-11-08 | 2014-04-29 | The General Hospital Corporation | Procedimientos y composiciones de tratamiento de enfermedades proteinúricas |
| MX2011012345A (es) | 2009-05-22 | 2012-01-31 | Exelixis Inc | Inhibidores de pi3k/mtor basados en benzoxazepinas contra enfermedades proliferativas. |
| JP2012528079A (ja) | 2009-05-25 | 2012-11-12 | 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の連続投与 |
| JP5791628B2 (ja) * | 2009-12-17 | 2015-10-07 | ビーエーエスエフ ソシエタス・ヨーロピアBasf Se | 高級エタノールアミンの製造方法 |
| AU2010363329A1 (en) | 2010-11-07 | 2013-05-09 | Targegen, Inc. | Compositions and methods for treating myelofibrosis |
| SG11201609050UA (en) | 2014-05-30 | 2016-12-29 | Pfizer | Carbonitrile derivatives as selective androgen receptor modulators |
| SG11201809559UA (en) | 2016-06-13 | 2018-12-28 | Glaxosmithkline Ip Dev Ltd | Substituted pyridines as inhibitors of dnmt1 |
| EP3589285A4 (en) | 2017-02-28 | 2020-08-12 | Morphic Therapeutic, Inc. | INHIBITORS OF INTEGRIN (ALPHA-V) (BETA-6) |
| KR102605460B1 (ko) * | 2017-02-28 | 2023-11-22 | 모픽 테라퓨틱, 인코포레이티드 | αvβ6 인테그린 억제제 |
| MX2021002181A (es) | 2018-08-29 | 2021-07-15 | Morphic Therapeutic Inc | Inhibicion de la integrina alfa v beta 6. |
| WO2023275715A1 (en) | 2021-06-30 | 2023-01-05 | Pfizer Inc. | Metabolites of selective androgen receptor modulators |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3627754A (en) * | 1970-05-13 | 1971-12-14 | Hoffmann La Roche | Process for preparing 7-lower alkanoyl benzodiazepines utilizing ceric salts |
| EP0593603B1 (en) * | 1991-06-28 | 2002-11-20 | Smithkline Beecham Corporation | Bicyclic fibrinogen antagonists |
| SG90035A1 (en) * | 1992-12-21 | 2002-07-23 | Smithkline Beecham Corp | Bicyclic fibrinogen antagonists |
| ZA955391B (en) * | 1994-06-29 | 1996-02-09 | Smithkline Beecham Corp | Vitronectin receptor antagonists |
| CZ203898A3 (cs) * | 1995-12-29 | 1999-03-17 | Smithkline Beecham Corporation | Antagonista vitronektinového receptoru, farmaceutický přípravek s jeho obsahem, způsob a použití |
| ZA9610853B (en) * | 1995-12-29 | 1998-04-06 | Smithkline Beecham Corp | Processes and intermediates for preparing pharmaceuticals. |
-
1996
- 1996-12-20 EP EP96945085A patent/EP0895475A4/en not_active Withdrawn
- 1996-12-20 JP JP9524556A patent/JP2000502708A/ja active Pending
- 1996-12-20 KR KR1019980705003A patent/KR19990076876A/ko not_active Withdrawn
- 1996-12-20 WO PCT/US1996/020744 patent/WO1997024122A1/en not_active Ceased
- 1996-12-20 HU HU9901116A patent/HUP9901116A2/hu unknown
- 1996-12-20 IL IL12503496A patent/IL125034A0/xx unknown
- 1996-12-20 CN CN96180099A patent/CN1209060A/zh active Pending
- 1996-12-20 CZ CZ982037A patent/CZ203798A3/cs unknown
- 1996-12-20 AU AU13538/97A patent/AU1353897A/en not_active Abandoned
- 1996-12-20 PL PL96327919A patent/PL327919A1/xx unknown
- 1996-12-20 BR BR9612378A patent/BR9612378A/pt unknown
- 1996-12-20 TR TR1998/01255T patent/TR199801255T2/xx unknown
- 1996-12-20 CA CA002241724A patent/CA2241724A1/en not_active Abandoned
- 1996-12-23 ZA ZA9610855A patent/ZA9610855B/xx unknown
-
1998
- 1998-06-26 NO NO983002A patent/NO983002L/no not_active Application Discontinuation
- 1998-06-26 MX MX9805253A patent/MX9805253A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR19990076876A (ko) | 1999-10-25 |
| NO983002D0 (no) | 1998-06-26 |
| MX9805253A (es) | 1998-10-31 |
| CZ203798A3 (cs) | 1998-12-16 |
| WO1997024122A1 (en) | 1997-07-10 |
| HUP9901116A2 (hu) | 2000-03-28 |
| TR199801255T2 (xx) | 1998-10-21 |
| EP0895475A4 (en) | 2000-08-23 |
| NO983002L (no) | 1998-08-26 |
| AU1353897A (en) | 1997-07-28 |
| EP0895475A1 (en) | 1999-02-10 |
| BR9612378A (pt) | 1999-07-13 |
| JP2000502708A (ja) | 2000-03-07 |
| CN1209060A (zh) | 1999-02-24 |
| PL327919A1 (en) | 1999-01-04 |
| ZA9610855B (en) | 1997-11-24 |
| IL125034A0 (en) | 1999-01-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |