CA1314562C - Antiarthritic beta-cyclo-alkyl-beta-oxopropionitriles - Google Patents
Antiarthritic beta-cyclo-alkyl-beta-oxopropionitrilesInfo
- Publication number
- CA1314562C CA1314562C CA000589229A CA589229A CA1314562C CA 1314562 C CA1314562 C CA 1314562C CA 000589229 A CA000589229 A CA 000589229A CA 589229 A CA589229 A CA 589229A CA 1314562 C CA1314562 C CA 1314562C
- Authority
- CA
- Canada
- Prior art keywords
- compound
- 5alkyl
- alkyl
- beta
- solution
- 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.)
- Expired - Fee Related
Links
- 230000002456 anti-arthritic effect Effects 0.000 title claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 68
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 3
- 101150009274 nhr-1 gene Proteins 0.000 claims abstract 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 238000000034 method Methods 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 125000000217 alkyl group Chemical group 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- 239000007787 solid Substances 0.000 description 14
- 210000002683 foot Anatomy 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 241000700159 Rattus Species 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 235000010418 carrageenan Nutrition 0.000 description 9
- 229920001525 carrageenan Polymers 0.000 description 9
- -1 tri-substituted phenyl Chemical group 0.000 description 9
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 8
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- 150000003857 carboxamides Chemical class 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 6
- 230000002917 arthritic effect Effects 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 230000005951 type IV hypersensitivity Effects 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000003960 organic solvent 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
- 238000002360 preparation method Methods 0.000 description 5
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 5
- 206010030113 Oedema Diseases 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 229940124346 antiarthritic agent Drugs 0.000 description 4
- 239000003435 antirheumatic agent Substances 0.000 description 4
- 206010003246 arthritis Diseases 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000725 suspension Substances 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
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 241000186359 Mycobacterium Species 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
- 150000001412 amines Chemical class 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 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 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- BWUJGSRMXDBSPJ-UHFFFAOYSA-N O=C=C1NC=CN1 Chemical compound O=C=C1NC=CN1 BWUJGSRMXDBSPJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 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
- 150000001408 amides Chemical class 0.000 description 2
- 239000000538 analytical sample Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 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
- 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 2
- 238000002651 drug therapy Methods 0.000 description 2
- 210000005069 ears Anatomy 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 210000000548 hind-foot Anatomy 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 150000002513 isocyanates Chemical class 0.000 description 2
- 238000011694 lewis rat Methods 0.000 description 2
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 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
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 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
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000007142 ring opening reaction Methods 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 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
- 238000005303 weighing Methods 0.000 description 2
- LKYNGTHMKCTTQC-UHFFFAOYSA-N 1,2-oxazole-3-carboxamide Chemical compound NC(=O)C=1C=CON=1 LKYNGTHMKCTTQC-UHFFFAOYSA-N 0.000 description 1
- UXYRXGFUANQKTA-UHFFFAOYSA-N 1,2-oxazole-3-carboxylic acid Chemical compound OC(=O)C=1C=CON=1 UXYRXGFUANQKTA-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
- VXRDAMSNTXUHFX-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid;n,n-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide Chemical compound OC(=O)C(O)C(O)C(O)=O.N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1.N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 VXRDAMSNTXUHFX-UHFFFAOYSA-N 0.000 description 1
- SURCGQGDUADKBL-UHFFFAOYSA-N 2-(2-hydroxyethylamino)-5-nitrobenzo[de]isoquinoline-1,3-dione Chemical class [O-][N+](=O)C1=CC(C(N(NCCO)C2=O)=O)=C3C2=CC=CC3=C1 SURCGQGDUADKBL-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
- YNTJKQDWYXUTLZ-UHFFFAOYSA-N 2-(3-chlorophenoxy)propanoic acid Chemical compound OC(=O)C(C)OC1=CC=CC(Cl)=C1 YNTJKQDWYXUTLZ-UHFFFAOYSA-N 0.000 description 1
- ORMIKPSLLOLDGT-UHFFFAOYSA-N 2-acetyl-3-oxobutanenitrile Chemical compound CC(=O)C(C#N)C(C)=O ORMIKPSLLOLDGT-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
- IPMQSLPLJDKUPI-UHFFFAOYSA-N 2-oxocyclopentane-1-carbonitrile Chemical compound O=C1CCCC1C#N IPMQSLPLJDKUPI-UHFFFAOYSA-N 0.000 description 1
- FJPUKTJEFOXMJX-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[1-(hydroxymethyl)cyclopropyl]benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NC2(CC2)CO)C=CC=1 FJPUKTJEFOXMJX-UHFFFAOYSA-N 0.000 description 1
- CICCSFJDNVHXJD-UHFFFAOYSA-N 3-amino-2-cyano-3-oxopropanoic acid Chemical class NC(=O)C(C#N)C(O)=O CICCSFJDNVHXJD-UHFFFAOYSA-N 0.000 description 1
- KIJMAOMSRMPYIY-UHFFFAOYSA-N 5-cyclopropyl-1,2-oxazole-4-carboxylic acid Chemical compound C1=NOC(C2CC2)=C1C(=O)O KIJMAOMSRMPYIY-UHFFFAOYSA-N 0.000 description 1
- AGQOIYCTCOEHGR-UHFFFAOYSA-N 5-methyl-1,2-oxazole Chemical compound CC1=CC=NO1 AGQOIYCTCOEHGR-UHFFFAOYSA-N 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
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 208000006313 Delayed Hypersensitivity Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 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
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 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
- 229930195725 Mannitol Natural products 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010036030 Polyarthritis Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 229940045942 acetone sodium bisulfite Drugs 0.000 description 1
- QLDHWVVRQCGZLE-UHFFFAOYSA-N acetyl cyanide Chemical compound CC(=O)C#N QLDHWVVRQCGZLE-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 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
- 239000002671 adjuvant Substances 0.000 description 1
- 239000008272 agar Substances 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
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 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
- 125000000304 alkynyl group Chemical group 0.000 description 1
- HXBPYFMVGFDZFT-UHFFFAOYSA-N allyl isocyanate Chemical compound C=CCN=C=O HXBPYFMVGFDZFT-UHFFFAOYSA-N 0.000 description 1
- 229940094070 ambien Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000008064 anhydrides Chemical class 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
- 239000003125 aqueous solvent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [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
- 229960004217 benzyl alcohol Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000003086 colorant Substances 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
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- LMBWSYZSUOEYSN-UHFFFAOYSA-N diethyldithiocarbamic acid Chemical compound CCN(CC)C(S)=S LMBWSYZSUOEYSN-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 239000003085 diluting agent Substances 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
- 238000011549 displacement method Methods 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 229950004394 ditiocarb Drugs 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 230000000857 drug effect Effects 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
- 150000002148 esters Chemical class 0.000 description 1
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 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
- 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
- 125000001145 hydrido group Chemical group *[H] 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
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229940060367 inert ingredients Drugs 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-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
- 230000003908 liver function Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- HCTVWSOKIJULET-LQDWTQKMSA-M phenoxymethylpenicillin potassium Chemical compound [K+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)COC1=CC=CC=C1 HCTVWSOKIJULET-LQDWTQKMSA-M 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
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 208000030428 polyarticular arthritis Diseases 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
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 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
- HBROZNQEVUILML-UHFFFAOYSA-N salicylhydroxamic acid Chemical compound ONC(=O)C1=CC=CC=C1O HBROZNQEVUILML-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- YNJORDSKPXMABC-UHFFFAOYSA-M sodium;2-hydroxypropane-2-sulfonate Chemical compound [Na+].CC(C)(O)S([O-])(=O)=O YNJORDSKPXMABC-UHFFFAOYSA-M 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
- 239000007858 starting material Substances 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 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
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- UBBZKZRMWONRRS-UHFFFAOYSA-N thionyl dichloride hydrochloride Chemical compound Cl.ClS(Cl)=O UBBZKZRMWONRRS-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 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
- 238000001665 trituration 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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (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)
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 |
| US148,540 | 1988-01-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1314562C true CA1314562C (en) | 1993-03-16 |
Family
ID=22526203
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000589229A Expired - Fee Related CA1314562C (en) | 1988-01-26 | 1989-01-26 | Antiarthritic beta-cyclo-alkyl-beta-oxopropionitriles |
Country Status (7)
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL92508A0 (en) * | 1988-12-08 | 1990-08-31 | Ciba Geigy Ag | Novel alpha-cyano-beta-oxopropionamides |
| GB9023535D0 (en) * | 1990-10-30 | 1990-12-12 | Roussel Lab Ltd | Chemical compounds |
| 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 |
| 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 |
| JP5544892B2 (ja) * | 2010-01-19 | 2014-07-09 | 日亜化学工業株式会社 | ２−シアノ−１，３−ジケトネート塩の製造法及びイオン液体 |
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 |
| US4254048A (en) * | 1979-12-17 | 1981-03-03 | American Cyanamid Company | Substituted phenyl alkylidene acetoacetonitriles |
| US4254049A (en) * | 1979-12-17 | 1981-03-03 | American Cyanamid Company | Substituted phenyl-2-cyano-2-alkenoic acid esters |
| 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 AT AT89101278T patent/ATE80157T1/de not_active IP Right Cessation
- 1989-01-25 EP EP89101278A patent/EP0326107B1/en not_active Expired - Lifetime
- 1989-01-25 JP JP1014212A patent/JPH021451A/ja active Granted
- 1989-01-25 DE DE8989101278T patent/DE68902647T2/de not_active Expired - Fee Related
- 1989-01-26 CA CA000589229A patent/CA1314562C/en not_active Expired - Fee Related
-
1992
- 1992-09-03 GR GR920401727T patent/GR3005584T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GR3005584T3 (US06380249-20020430-C00031.png) | 1993-06-07 |
| EP0326107B1 (en) | 1992-09-02 |
| JPH021451A (ja) | 1990-01-05 |
| ATE80157T1 (de) | 1992-09-15 |
| US4888357A (en) | 1989-12-19 |
| DE68902647D1 (en) | 1992-10-08 |
| EP0326107A1 (en) | 1989-08-02 |
| JPH0567616B2 (US06380249-20020430-C00031.png) | 1993-09-27 |
| DE68902647T2 (de) | 1993-02-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0138464B1 (en) | 2-amino-5-hydroxy-4-methylpyrimidine derivatives | |
| US5366992A (en) | Benzoic acid substituted derivatives having cardiovascular activity | |
| CA1314562C (en) | Antiarthritic beta-cyclo-alkyl-beta-oxopropionitriles | |
| RU2109735C1 (ru) | Оксопропаннитрильные производные конденсированного пиразола или их фармацевтически приемлемые соли, проявляющие иммуностимулирующую активность, и фармацевтическая композиция | |
| US5166152A (en) | Tricyclic 3-oxo-propanenitrile derivatives | |
| US4499286A (en) | Derivatives of thienylacetic acid amides and their pharmaceutically acceptable acid salts and a process for the preparation thereof | |
| US4935434A (en) | Antiarthritic isoxazole-4-carboxamides | |
| AU637513B2 (en) | Substituted phenylacetylenes, pharmaceutical compositions containing these compounds and processes for the preparation of these compounds and compositions | |
| KR900003270B1 (ko) | N,n-2 치환된 카르복실산 아미드류의 제조방법 | |
| US4673677A (en) | Method for treatment of gastrointestinal disorders | |
| US4975462A (en) | Antiarthritic α-arylcarbamoyl cyanoacetic acid derivatives | |
| EP0372470A2 (en) | Novel alpha-cyano-beta-oxopropionamides | |
| US4988711A (en) | HMG-CoA reductare-inhibiting N-substituted N-amino-pyrroles | |
| US4198509A (en) | Mercaptoacylpiperazine carboxylic acid compounds | |
| US4584385A (en) | Antibacterial 2-amino-oxazolinones and process therefor | |
| US3576819A (en) | Esters of alpha-(1-substituted-3-pyrrolidinyl)-alpha-phenyl acetic acid | |
| JP3035074B2 (ja) | イソオキサゾリン誘導体およびそれを有効成分とする抗ウィルス剤 | |
| US6897233B2 (en) | Peptide deformylase inhibitors | |
| US3036065A (en) | Dioxo-azetidines | |
| USRE31980E (en) | Olefinic derivatives of amino acids | |
| JP2974791B2 (ja) | カルボキシイミダミド誘導体 | |
| KR800001142B1 (ko) | 1-아지리딘-카아복실산 에스테르 유도체의 제조법 | |
| US4629794A (en) | Antibacterial 2-amino-oxazolinones and process therefor | |
| FI95911C (fi) | Menetelmä terapeuttisesti käyttökelpoisten N-alkenyylibentso/b/tieno-/3,2-b/oksatsiini-2,4-dionien valmistamiseksi | |
| US4294830A (en) | {[[4-Azido-5-(ethoxyethyl)-6-phenyl-2-pyrimidinyl]amino]carbonyl}glycine and esters thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKLA | Lapsed |