JP2002511462A - ビトロネクチンアンタゴニストとしてのヘテロ環式グリシルβ−アラニン誘導体 - Google Patents
ビトロネクチンアンタゴニストとしてのヘテロ環式グリシルβ−アラニン誘導体Info
- Publication number
- JP2002511462A JP2002511462A JP2000543454A JP2000543454A JP2002511462A JP 2002511462 A JP2002511462 A JP 2002511462A JP 2000543454 A JP2000543454 A JP 2000543454A JP 2000543454 A JP2000543454 A JP 2000543454A JP 2002511462 A JP2002511462 A JP 2002511462A
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- JP
- Japan
- Prior art keywords
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- aryl
- alkyl
- product
- image embedded
- 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
- -1 Heterocyclic glycyl β-alanine derivatives Chemical class 0.000 title claims description 115
- 239000005557 antagonist Substances 0.000 title description 11
- 108010031318 Vitronectin Proteins 0.000 title description 8
- 102100035140 Vitronectin Human genes 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 196
- 238000000034 method Methods 0.000 claims abstract description 105
- 108010044426 integrins Proteins 0.000 claims abstract description 25
- 102000006495 integrins Human genes 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 230000001404 mediated effect Effects 0.000 claims abstract description 4
- 125000003118 aryl group Chemical group 0.000 claims description 123
- 125000000217 alkyl group Chemical group 0.000 claims description 106
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 75
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 69
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 53
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 52
- 229910052757 nitrogen Inorganic materials 0.000 claims description 52
- 125000003545 alkoxy group Chemical group 0.000 claims description 49
- 125000001188 haloalkyl group Chemical group 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- 239000001257 hydrogen Substances 0.000 claims description 39
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 35
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 32
- 125000001424 substituent group Chemical group 0.000 claims description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 25
- 125000004414 alkyl thio group Chemical group 0.000 claims description 25
- 125000004104 aryloxy group Chemical group 0.000 claims description 25
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 23
- 229910052717 sulfur Inorganic materials 0.000 claims description 23
- 125000003342 alkenyl group Chemical group 0.000 claims description 22
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 22
- 125000000304 alkynyl group Chemical group 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 206010028980 Neoplasm Diseases 0.000 claims description 19
- 125000003282 alkyl amino group Chemical group 0.000 claims description 19
- 150000002148 esters Chemical class 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 17
- 229940124530 sulfonamide Drugs 0.000 claims description 17
- 150000003456 sulfonamides Chemical class 0.000 claims description 17
- 125000005843 halogen group Chemical group 0.000 claims description 16
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 15
- 150000001408 amides Chemical class 0.000 claims description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 12
- 125000004442 acylamino group Chemical group 0.000 claims description 11
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 11
- 230000033115 angiogenesis Effects 0.000 claims description 11
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 11
- 125000004692 haloalkylcarbonyl group Chemical group 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 125000002950 monocyclic group Chemical group 0.000 claims description 10
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 9
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 125000004993 haloalkoxycarbonyl group Chemical group 0.000 claims description 8
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- 208000001132 Osteoporosis Diseases 0.000 claims description 7
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- 208000037803 restenosis Diseases 0.000 claims description 7
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 7
- 206010027476 Metastases Diseases 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 208000002780 macular degeneration Diseases 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
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- 208000037147 Hypercalcaemia Diseases 0.000 claims description 5
- 125000005361 aryl sulfoxide group Chemical group 0.000 claims description 5
- 125000005110 aryl thio group Chemical group 0.000 claims description 5
- 125000002619 bicyclic group Chemical group 0.000 claims description 5
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 5
- 125000004122 cyclic group Chemical group 0.000 claims description 5
- 230000000148 hypercalcaemia Effects 0.000 claims description 5
- 208000030915 hypercalcemia disease Diseases 0.000 claims description 5
- 230000003211 malignant effect Effects 0.000 claims description 5
- 230000009401 metastasis Effects 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
- 125000000094 2-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 4
- 229930194542 Keto Natural products 0.000 claims description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000000468 ketone group Chemical group 0.000 claims description 4
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- VQJYYAYBKBRRDJ-UHFFFAOYSA-N 1-(2,6-difluorophenyl)-1,3-dihydro-[1,3]thiazolo[3,4-a]benzimidazole 2-oxide Chemical compound FC1=CC=CC(F)=C1C1S(=O)CC2=NC3=CC=CC=C3N12 VQJYYAYBKBRRDJ-UHFFFAOYSA-N 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 3
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 3
- 125000005360 alkyl sulfoxide group Chemical group 0.000 claims description 3
- 125000001769 aryl amino group Chemical group 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical class O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 claims description 3
- 150000003007 phosphonic acid derivatives Chemical class 0.000 claims description 3
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 3
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 2
- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical class C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 claims description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
- 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 2
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 2
- 125000004421 aryl sulphonamide group Chemical group 0.000 claims description 2
- 125000005605 benzo group Chemical group 0.000 claims description 2
- 125000005111 carboxyalkoxy group Chemical group 0.000 claims description 2
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 2
- 230000012010 growth Effects 0.000 claims description 2
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 2
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 2
- 125000000232 haloalkynyl group Chemical group 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 claims description 2
- 150000003431 steroids Chemical class 0.000 claims description 2
- 235000000346 sugar Nutrition 0.000 claims description 2
- 125000004001 thioalkyl group Chemical group 0.000 claims description 2
- 125000004950 trifluoroalkyl group Chemical group 0.000 claims description 2
- 229910052727 yttrium Inorganic materials 0.000 claims description 2
- 150000001413 amino acids Chemical class 0.000 claims 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims 1
- 239000000047 product Substances 0.000 description 331
- 239000000243 solution Substances 0.000 description 222
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 216
- 239000007787 solid Substances 0.000 description 168
- 238000005160 1H NMR spectroscopy Methods 0.000 description 157
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 150
- 238000006243 chemical reaction Methods 0.000 description 128
- 239000000203 mixture Substances 0.000 description 122
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 115
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 108
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 105
- 239000000460 chlorine Substances 0.000 description 98
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 96
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 95
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 93
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical group CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 86
- 229910001868 water Inorganic materials 0.000 description 83
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 75
- 235000019439 ethyl acetate Nutrition 0.000 description 74
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 67
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 66
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 59
- 238000004519 manufacturing process Methods 0.000 description 50
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 48
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 36
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- 238000000746 purification Methods 0.000 description 35
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- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 14
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- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- RNULVIMVPASZND-UHFFFAOYSA-N tert-butyl 2-methylsulfanyl-4,5-dihydroimidazole-1-carboxylate Chemical compound CSC1=NCCN1C(=O)OC(C)(C)C RNULVIMVPASZND-UHFFFAOYSA-N 0.000 description 1
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- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
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- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
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- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
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- 241000701161 unidentified adenovirus Species 0.000 description 1
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Classifications
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- 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
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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
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms 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
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
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US8139498P | 1998-04-10 | 1998-04-10 | |
US60/081,394 | 1998-04-10 | ||
PCT/US1999/004297 WO1999052896A1 (en) | 1998-04-10 | 1999-04-09 | Heterocyclic glycyl beta-alanine derivatives as vitronectin antagonists |
Publications (1)
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JP2002511462A true JP2002511462A (ja) | 2002-04-16 |
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JP2000543454A Pending JP2002511462A (ja) | 1998-04-10 | 1999-04-09 | ビトロネクチンアンタゴニストとしてのヘテロ環式グリシルβ−アラニン誘導体 |
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EP (1) | EP1070060A1 (cs) |
JP (1) | JP2002511462A (cs) |
KR (1) | KR20010042614A (cs) |
CN (1) | CN1304406A (cs) |
AR (1) | AR015759A1 (cs) |
AU (1) | AU765294B2 (cs) |
BR (1) | BR9910119A (cs) |
CA (1) | CA2326665A1 (cs) |
CZ (1) | CZ20003672A3 (cs) |
IL (1) | IL138677A0 (cs) |
MY (1) | MY133473A (cs) |
NO (1) | NO20005084L (cs) |
NZ (1) | NZ507292A (cs) |
PL (1) | PL343406A1 (cs) |
RU (1) | RU2215746C2 (cs) |
TW (1) | TWI247008B (cs) |
WO (1) | WO1999052896A1 (cs) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002541257A (ja) * | 1999-04-12 | 2002-12-03 | アベンティス・フアーマ・リミテッド | インテグリンアンタゴニストとしての置換された二環式ヘテロアリール化合物 |
JP2005519929A (ja) * | 2002-02-06 | 2005-07-07 | 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 ハフトング | インテグリンαvβ6の阻害剤 |
JP2011504481A (ja) * | 2007-11-22 | 2011-02-10 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 有機化合物 |
JP2020500182A (ja) * | 2016-11-08 | 2020-01-09 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | アルファvインテグリン阻害剤としてのピロールアミド |
WO2021230325A1 (ja) * | 2020-05-14 | 2021-11-18 | 宇部興産株式会社 | 1,4,5,6-テトラヒドロピリミジン-2-アミン誘導体 |
WO2023085396A1 (ja) * | 2021-11-12 | 2023-05-19 | Ube株式会社 | アルポート症候群を治療または予防するための医薬組成物 |
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Publication number | Priority date | Publication date | Assignee | Title |
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US6172256B1 (en) * | 1998-03-04 | 2001-01-09 | G.D. Searle & Co. | Chiral-β-amino acid compounds and derivatives thereof |
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 |
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 |
GB9826174D0 (en) | 1998-11-30 | 1999-01-20 | Celltech Therapeutics Ltd | Chemical compounds |
BR9916518A (pt) * | 1998-12-23 | 2002-01-29 | Searle & Co | Método para tratar ou prevenir um distúrbio de neoplasia em um mamìfero em necessidade de tal tratamento ou prevenção, e, combinação compreendendo um inibidor de ciclooxigenase-2 e um ou mais agentes anti-neoplásticos |
US6297233B1 (en) | 1999-02-09 | 2001-10-02 | Bristol-Myers Squibb Company | Lactam inhibitors of FXa and method |
HK1044937A1 (zh) * | 1999-04-12 | 2002-11-08 | Aventis Pharma Limited | 作為整聯蛋白拮抗物的取代的雙環雜芳基化合物 |
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- 1999-04-09 BR BR9910119-0A patent/BR9910119A/pt not_active IP Right Cessation
- 1999-04-09 CZ CZ20003672A patent/CZ20003672A3/cs unknown
- 1999-04-09 AU AU34499/99A patent/AU765294B2/en not_active Ceased
- 1999-04-09 AR ARP990101636A patent/AR015759A1/es unknown
- 1999-04-09 KR KR1020007011291A patent/KR20010042614A/ko not_active Ceased
- 1999-04-09 IL IL13867799A patent/IL138677A0/xx unknown
- 1999-04-09 CA CA002326665A patent/CA2326665A1/en not_active Abandoned
- 1999-04-09 RU RU2000128033/04A patent/RU2215746C2/ru not_active IP Right Cessation
- 1999-04-09 CN CN99807091A patent/CN1304406A/zh active Pending
- 1999-04-09 JP JP2000543454A patent/JP2002511462A/ja active Pending
- 1999-04-09 NZ NZ507292A patent/NZ507292A/en unknown
- 1999-04-09 TW TW088105718A patent/TWI247008B/zh active
- 1999-04-09 EP EP99916119A patent/EP1070060A1/en not_active Withdrawn
- 1999-04-09 WO PCT/US1999/004297 patent/WO1999052896A1/en not_active Application Discontinuation
- 1999-04-09 PL PL99343406A patent/PL343406A1/xx unknown
- 1999-04-10 MY MYPI99001398A patent/MY133473A/en unknown
-
2000
- 2000-10-09 NO NO20005084A patent/NO20005084L/no not_active Application Discontinuation
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JP2002541257A (ja) * | 1999-04-12 | 2002-12-03 | アベンティス・フアーマ・リミテッド | インテグリンアンタゴニストとしての置換された二環式ヘテロアリール化合物 |
JP4864206B2 (ja) * | 1999-04-12 | 2012-02-01 | アベンティス・フアーマ・リミテッド | インテグリンアンタゴニストとしての置換された二環式ヘテロアリール化合物 |
JP2005519929A (ja) * | 2002-02-06 | 2005-07-07 | 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 ハフトング | インテグリンαvβ6の阻害剤 |
JP2011504481A (ja) * | 2007-11-22 | 2011-02-10 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 有機化合物 |
JP2020500182A (ja) * | 2016-11-08 | 2020-01-09 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | アルファvインテグリン阻害剤としてのピロールアミド |
JP7220653B2 (ja) | 2016-11-08 | 2023-02-10 | ブリストル-マイヤーズ スクイブ カンパニー | アルファvインテグリン阻害剤としてのピロールアミド |
WO2021230325A1 (ja) * | 2020-05-14 | 2021-11-18 | 宇部興産株式会社 | 1,4,5,6-テトラヒドロピリミジン-2-アミン誘導体 |
CN115551846A (zh) * | 2020-05-14 | 2022-12-30 | Ube株式会社 | 1,4,5,6-四氢嘧啶-2-胺衍生物 |
CN115551846B (zh) * | 2020-05-14 | 2024-03-08 | Ube株式会社 | 1,4,5,6-四氢嘧啶-2-胺衍生物 |
JP7661969B2 (ja) | 2020-05-14 | 2025-04-15 | Ube株式会社 | 1,4,5,6-テトラヒドロピリミジン-2-アミン誘導体 |
WO2023085396A1 (ja) * | 2021-11-12 | 2023-05-19 | Ube株式会社 | アルポート症候群を治療または予防するための医薬組成物 |
Also Published As
Publication number | Publication date |
---|---|
TWI247008B (en) | 2006-01-11 |
EP1070060A1 (en) | 2001-01-24 |
AR015759A1 (es) | 2001-05-16 |
IL138677A0 (en) | 2001-10-31 |
BR9910119A (pt) | 2001-10-09 |
RU2215746C2 (ru) | 2003-11-10 |
CZ20003672A3 (cs) | 2001-08-15 |
CA2326665A1 (en) | 1999-10-21 |
MY133473A (en) | 2007-11-30 |
KR20010042614A (ko) | 2001-05-25 |
NZ507292A (en) | 2003-12-19 |
AU765294B2 (en) | 2003-09-11 |
PL343406A1 (en) | 2001-08-13 |
WO1999052896A1 (en) | 1999-10-21 |
CN1304406A (zh) | 2001-07-18 |
AU3449999A (en) | 1999-11-01 |
NO20005084L (no) | 2000-11-27 |
NO20005084D0 (no) | 2000-10-09 |
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