JPH021451A - 抗関節炎性β―シクロアルキル―β―オキソプロピオニトリル類 - Google Patents
抗関節炎性β―シクロアルキル―β―オキソプロピオニトリル類Info
- Publication number
- JPH021451A JPH021451A JP1014212A JP1421289A JPH021451A JP H021451 A JPH021451 A JP H021451A JP 1014212 A JP1014212 A JP 1014212A JP 1421289 A JP1421289 A JP 1421289A JP H021451 A JPH021451 A JP H021451A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- compound according
- formula
- cycloalkyl
- arthritic
- 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.)
- Granted
Links
- 230000002456 anti-arthritic effect Effects 0.000 title description 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 31
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 6
- 229940124346 antiarthritic agent Drugs 0.000 claims abstract description 5
- 239000003435 antirheumatic agent Substances 0.000 claims abstract description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- 239000002260 anti-inflammatory agent Substances 0.000 claims abstract description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 60
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 1
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 16
- 150000001412 amines Chemical class 0.000 abstract description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 abstract description 4
- 150000001408 amides Chemical class 0.000 abstract description 3
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 abstract description 2
- 150000008065 acid anhydrides Chemical class 0.000 abstract description 2
- UXYRXGFUANQKTA-UHFFFAOYSA-N 1,2-oxazole-3-carboxylic acid Chemical compound OC(=O)C=1C=CON=1 UXYRXGFUANQKTA-UHFFFAOYSA-N 0.000 abstract 1
- AIGJJRCKEIQZBQ-UHFFFAOYSA-N 2-cyano-3-cyclopropyl-n-methyl-3-oxopropanamide Chemical compound CNC(=O)C(C#N)C(=O)C1CC1 AIGJJRCKEIQZBQ-UHFFFAOYSA-N 0.000 abstract 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 abstract 1
- 230000001741 anti-phlogistic effect Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 239000007787 solid Substances 0.000 description 13
- -1 tri-substituted phenyl Chemical group 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 230000003110 anti-inflammatory effect Effects 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- 150000003857 carboxamides Chemical class 0.000 description 7
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 235000010418 carrageenan Nutrition 0.000 description 6
- 229920001525 carrageenan Polymers 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 5
- 239000000679 carrageenan Substances 0.000 description 4
- 229940113118 carrageenan Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- ZMMOYIXZGHJMNI-UHFFFAOYSA-N 3-oxopropanenitrile Chemical compound O=CCC#N ZMMOYIXZGHJMNI-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000002917 arthritic effect Effects 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 210000003141 lower extremity Anatomy 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- SDARMQNRQJBGQE-UHFFFAOYSA-N 3-cyclopropyl-3-oxopropanenitrile Chemical compound N#CCC(=O)C1CC1 SDARMQNRQJBGQE-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 208000009386 Experimental Arthritis Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 241000186359 Mycobacterium Species 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 2
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- 210000005069 ears Anatomy 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 210000002683 foot Anatomy 0.000 description 2
- 210000000548 hind-foot Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 2
- 229960001005 tuberculin Drugs 0.000 description 2
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 1
- LKYNGTHMKCTTQC-UHFFFAOYSA-N 1,2-oxazole-3-carboxamide Chemical class NC(=O)C=1C=CON=1 LKYNGTHMKCTTQC-UHFFFAOYSA-N 0.000 description 1
- QBPXGTUBZXXKJO-UHFFFAOYSA-N 1,2-oxazole-4-carboxamide Chemical class NC(=O)C=1C=NOC=1 QBPXGTUBZXXKJO-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- GLPCMJHDPXSCPC-UHFFFAOYSA-N 2-cyano-4-hydroxy-n-phenylbut-2-enamide Chemical class OCC=C(C#N)C(=O)NC1=CC=CC=C1 GLPCMJHDPXSCPC-UHFFFAOYSA-N 0.000 description 1
- LUCVZEPCGGHKOM-UHFFFAOYSA-N 2-cyano-n,3-dicyclopropyl-3-oxopropanamide Chemical compound C1CC1C(=O)C(C#N)C(=O)NC1CC1 LUCVZEPCGGHKOM-UHFFFAOYSA-N 0.000 description 1
- BWLBGMIXKSTLSX-UHFFFAOYSA-N 2-hydroxyisobutyric acid Chemical compound CC(C)(O)C(O)=O BWLBGMIXKSTLSX-UHFFFAOYSA-N 0.000 description 1
- IPMQSLPLJDKUPI-UHFFFAOYSA-N 2-oxocyclopentane-1-carbonitrile Chemical compound O=C1CCCC1C#N IPMQSLPLJDKUPI-UHFFFAOYSA-N 0.000 description 1
- LGAJCZJGBNGDFR-UHFFFAOYSA-N 3-cyclopropyl-3-oxopropanoic acid Chemical compound OC(=O)CC(=O)C1CC1 LGAJCZJGBNGDFR-UHFFFAOYSA-N 0.000 description 1
- HRRWQQNTPXPXEG-UHFFFAOYSA-N 5-cyclopropyl-1,2-oxazole-4-carbonyl chloride Chemical compound C1=NOC(C2CC2)=C1C(=O)Cl HRRWQQNTPXPXEG-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- 229940127007 Compound 39 Drugs 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000087799 Koma Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- BWUJGSRMXDBSPJ-UHFFFAOYSA-N O=C=C1NC=CN1 Chemical compound O=C=C1NC=CN1 BWUJGSRMXDBSPJ-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000000538 analytical sample Substances 0.000 description 1
- 230000000507 anthelmentic effect Effects 0.000 description 1
- 239000000921 anthelmintic agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- ZJRCIQAMTAINCB-UHFFFAOYSA-N benzoylacetonitrile Chemical compound N#CCC(=O)C1=CC=CC=C1 ZJRCIQAMTAINCB-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000002508 compound effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 description 1
- TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 description 1
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 150000002084 enol ethers Chemical class 0.000 description 1
- 125000002587 enol group Chemical group 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- LTZZYVWUGIPISL-UHFFFAOYSA-N ethyl(hydroxy)azanium;chloride Chemical compound [Cl-].CC[NH2+]O LTZZYVWUGIPISL-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- LFKYBJLFJOOKAE-UHFFFAOYSA-N imidazol-2-ylidenemethanone Chemical compound O=C=C1N=CC=N1 LFKYBJLFJOOKAE-UHFFFAOYSA-N 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 229940060367 inert ingredients Drugs 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 150000002545 isoxazoles Chemical class 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000011694 lewis rat Methods 0.000 description 1
- 208000014987 limb edema Diseases 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 150000003556 thioamides Chemical class 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 238000001521 two-tailed test Methods 0.000 description 1
- 230000005951 type IV hypersensitivity Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/31—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing rings other than six-membered aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Pharmacology & Pharmacy (AREA)
- Rheumatology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/148,540 US4888357A (en) | 1988-01-26 | 1988-01-26 | Antiarthritic β-cycloalkyl-β-oxopropionitriles |
| US148540 | 1988-01-26 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH021451A true JPH021451A (ja) | 1990-01-05 |
| JPH0567616B2 JPH0567616B2 (US06380249-20020430-C00031.png) | 1993-09-27 |
Family
ID=22526203
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1014212A Granted JPH021451A (ja) | 1988-01-26 | 1989-01-25 | 抗関節炎性β―シクロアルキル―β―オキソプロピオニトリル類 |
Country Status (7)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011148711A (ja) * | 2010-01-19 | 2011-08-04 | Nichia Corp | ２−シアノ−１，３−ジケトネート塩の製造法及びイオン液体 |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL92508A0 (en) * | 1988-12-08 | 1990-08-31 | Ciba Geigy Ag | Novel alpha-cyano-beta-oxopropionamides |
| IL99811A (en) * | 1990-10-30 | 1996-03-31 | Roussel Uclaf | 3-Cycloalkyl-propanamides, tautomeric forms of these, their salts, method of preparation, use as drugs and preparations containing them |
| GB9023535D0 (en) * | 1990-10-30 | 1990-12-12 | Roussel Lab Ltd | Chemical compounds |
| IL102790A (en) * | 1991-09-17 | 1996-01-31 | Roussel Uclaf | History of 3-cycloalkyl-prop-2-anamide |
| GB9300083D0 (en) | 1993-01-05 | 1993-03-03 | Roussel Lab Ltd | Chemical compounds |
| WO1994024095A1 (en) * | 1993-04-16 | 1994-10-27 | Abbott Laboratories | Immunosuppressive agents |
| JP2594965Y2 (ja) * | 1993-12-27 | 1999-05-24 | 株式会社柿崎製作所 | 道路付帯設備用支柱のキャップ |
| GB9405229D0 (en) * | 1994-03-17 | 1994-04-27 | Rhone Poulenc Agriculture | Compositions of matter |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3016295A (en) * | 1958-06-23 | 1962-01-09 | Du Pont | Method for altering the growth characteristics of plants |
| DE1237105B (de) * | 1965-06-26 | 1967-03-23 | Riedel De Haeen Ag | Verfahren zur Herstellung von Thiocarbonsaeureamiden |
| US3406183A (en) * | 1966-11-01 | 1968-10-15 | American Home Prod | 3-n-arylamino-3-mercapto-2-cyanoacrylamides |
| NL186239B (nl) * | 1975-06-05 | Hoechst Ag | Werkwijze voor de bereiding van een geneesmiddel met antiflogistische en/of analgetische werking, alsmede werkwijze voor de bereiding van een 2-hydroxyethylideencyaanazijnzuuranilide geschikt voor toepassing bij deze werkwijze. | |
| DE2555789A1 (de) * | 1975-12-11 | 1977-07-07 | Hoechst Ag | Neue cyanessigsaeureanilid-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende mittel |
| US4170656A (en) * | 1977-05-31 | 1979-10-09 | American Cyanamid Company | Compositions containing cis-2-benzoyl-3-hydroxy-crotononitrile used to treat inflammation and joint deterioration |
| US4189436A (en) * | 1977-11-22 | 1980-02-19 | American Cyanamid Company | β-oxo-3-thiophene propionitrile and β-amino-2-(3)-thiophene acrylonitriles |
| US4197310A (en) * | 1979-04-30 | 1980-04-08 | American Cyanamid Company | Thiophenepropionitriles |
| US4173650A (en) * | 1978-11-03 | 1979-11-06 | American Cyanamid Company | Cis-2-benzoyl-3-hydroxy-2-alkenonitriles as anti-inflammatory agents |
| US4256759A (en) * | 1979-06-11 | 1981-03-17 | Ciba-Geigy Corporation | Alphacarbamoyl-pyrrolpropionitriles |
| US4254047A (en) * | 1979-12-17 | 1981-03-03 | American Cyanamid Company | Substituted phenyl-2-cyano-2-thioalkenoic acid esters |
| US4254049A (en) * | 1979-12-17 | 1981-03-03 | American Cyanamid Company | Substituted phenyl-2-cyano-2-alkenoic acid esters |
| US4254048A (en) * | 1979-12-17 | 1981-03-03 | American Cyanamid Company | Substituted phenyl alkylidene acetoacetonitriles |
| US4435407A (en) * | 1982-01-07 | 1984-03-06 | Ciba-Geigy Corporation | Certain substituted β-oxo-α-carbamoylpyrrolepropionitriles |
| DE3209472C2 (de) * | 1982-03-16 | 1984-05-17 | Degussa Ag, 6000 Frankfurt | Verfahren zur Herstellung von 3-Oxonitrilen sowie neue 3-Oxonitrile |
| DE3217446A1 (de) * | 1982-05-08 | 1983-11-24 | A. Nattermann & Cie GmbH, 5000 Köln | Substituierte thiocarbamoyl-thenoylacetonitrile, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate |
| US4644010A (en) * | 1982-09-28 | 1987-02-17 | Ciba-Geigy Corporation | Certain β-oxo-α-carbamoylpyrrolepropionitriles |
| IL72093A0 (en) * | 1983-06-20 | 1984-10-31 | Lilly Co Eli | N'-substituted(3-alkyl-5-isothiazolyl)urea derivatives |
-
1988
- 1988-01-26 US US07/148,540 patent/US4888357A/en not_active Expired - Fee Related
-
1989
- 1989-01-25 EP EP89101278A patent/EP0326107B1/en not_active Expired - Lifetime
- 1989-01-25 AT AT89101278T patent/ATE80157T1/de not_active IP Right Cessation
- 1989-01-25 DE DE8989101278T patent/DE68902647T2/de not_active Expired - Fee Related
- 1989-01-25 JP JP1014212A patent/JPH021451A/ja active Granted
- 1989-01-26 CA CA000589229A patent/CA1314562C/en not_active Expired - Fee Related
-
1992
- 1992-09-03 GR GR920401727T patent/GR3005584T3/el unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011148711A (ja) * | 2010-01-19 | 2011-08-04 | Nichia Corp | ２−シアノ−１，３−ジケトネート塩の製造法及びイオン液体 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA1314562C (en) | 1993-03-16 |
| ATE80157T1 (de) | 1992-09-15 |
| JPH0567616B2 (US06380249-20020430-C00031.png) | 1993-09-27 |
| GR3005584T3 (US06380249-20020430-C00031.png) | 1993-06-07 |
| DE68902647T2 (de) | 1993-02-04 |
| EP0326107A1 (en) | 1989-08-02 |
| US4888357A (en) | 1989-12-19 |
| DE68902647D1 (en) | 1992-10-08 |
| EP0326107B1 (en) | 1992-09-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH05310672A (ja) | 新規な２−シアノ−３−ヒドロキシエナミド、それらの製造法、それらを含有する製薬組成物及びそれらの薬剤としての使用 | |
| JP3004728B2 (ja) | 神経伝達物質放出増強薬としての新規な非環式および環式アミド類 | |
| JPH021451A (ja) | 抗関節炎性β―シクロアルキル―β―オキソプロピオニトリル類 | |
| US4003909A (en) | [(1,2,4-Oxadiazol-3-yl)phenyl]carbamic or thiocarbamic acid esters | |
| Arenal et al. | Reaction of 4‐methylene‐5 (4H)‐oxazolones with diazomethane | |
| US3579529A (en) | Heterocyclic compounds | |
| US4987140A (en) | Pyridines | |
| US4935434A (en) | Antiarthritic isoxazole-4-carboxamides | |
| US5346912A (en) | 2-cyano-3-hydroxy-(n-pyridyl)-propenamide compounds | |
| JPH0649047A (ja) | フェニルカルボキサミドイソオキサゾールの新誘導体及びそれらの塩類、それらの製造法及びこの製造法の新規な中間体、それらの薬剤としての用途並びにそれらを含有する製薬組成物 | |
| US5416112A (en) | N-phenyl-2-cyano-3-hydroxy-propenamides | |
| EP0372470A2 (en) | Novel alpha-cyano-beta-oxopropionamides | |
| US3278544A (en) | Process for making beta-ketoamines | |
| EP0502110B1 (fr) | Derives d'(hetero) arylmethyloxy-4 phenyl diazole, leur procede de preparation et leur application en therapeutique | |
| JP4471663B2 (ja) | ペプチドデホルミラーゼ阻害剤 | |
| JPH01313460A (ja) | Ｎ‐置換されたｎ‐アミノ‐ピロール | |
| US6797730B2 (en) | Peptide deformylase inhibitors | |
| US6897233B2 (en) | Peptide deformylase inhibitors | |
| EP0047119B1 (en) | Carboxamide compounds as srs-a antagonists, pharmaceutical compositions containing them, processes for the preparation, and intermediates useful therein | |
| US4966975A (en) | Processes for the preparation of novel naphthalenylmethyl-3H-1,2,3,5-oxathiadiazole 2-oxides useful as antihyperglycemic agents | |
| JPH0670036B2 (ja) | ４ｈ−キノリジン−４−オン誘導体 | |
| EP0050977A1 (en) | Carboxamide compounds as SRS-A antagonists and a process for producing same | |
| KR800001142B1 (ko) | 1-아지리딘-카아복실산 에스테르 유도체의 제조법 | |
| JPH0670040B2 (ja) | ４ｈ−キノリジン−４−オン誘導体 | |
| JPH0670039B2 (ja) | ４ｈ−キノリジン−４−オン誘導体 |