CA1133917A - Alphacarbamoyl-pyrrolpropionitriles, process for their manufacture, pharmaceutical preparations containing these compounds and their therapeutic application - Google Patents
Alphacarbamoyl-pyrrolpropionitriles, process for their manufacture, pharmaceutical preparations containing these compounds and their therapeutic applicationInfo
- Publication number
- CA1133917A CA1133917A CA353,624A CA353624A CA1133917A CA 1133917 A CA1133917 A CA 1133917A CA 353624 A CA353624 A CA 353624A CA 1133917 A CA1133917 A CA 1133917A
- Authority
- CA
- Canada
- Prior art keywords
- base
- salt
- enol
- lower alkyl
- methyl
- 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
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 62
- 238000000034 method Methods 0.000 title claims abstract description 40
- 230000008569 process Effects 0.000 title claims abstract description 34
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 14
- 239000000825 pharmaceutical preparation Substances 0.000 title abstract description 4
- 230000001225 therapeutic effect Effects 0.000 title abstract description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 44
- -1 nitro, amino Chemical group 0.000 claims abstract description 42
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 39
- 239000001257 hydrogen Substances 0.000 claims abstract description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 20
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 15
- 125000005843 halogen group Chemical group 0.000 claims abstract description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 12
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 9
- 125000005236 alkanoylamino group Chemical group 0.000 claims abstract description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 6
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 5
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims abstract description 3
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims abstract description 3
- 125000002587 enol group Chemical group 0.000 claims abstract 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 54
- 239000000203 mixture Substances 0.000 claims description 47
- 239000002585 base Substances 0.000 claims description 40
- 150000002085 enols Chemical class 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 12
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000004997 halocarbonyl group Chemical group 0.000 claims description 4
- 230000003301 hydrolyzing effect Effects 0.000 claims description 4
- 150000002466 imines Chemical class 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 3
- 150000007530 organic bases Chemical class 0.000 claims description 3
- DSVGFKBFFICWLZ-UHFFFAOYSA-N 1-fluoro-4-isocyanatobenzene Chemical compound FC1=CC=C(N=C=O)C=C1 DSVGFKBFFICWLZ-UHFFFAOYSA-N 0.000 claims description 2
- 150000004678 hydrides Chemical class 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 claims 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 3
- 230000002456 anti-arthritic effect Effects 0.000 abstract description 2
- 125000001589 carboacyl group Chemical group 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 117
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 88
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 74
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 72
- 239000000243 solution Substances 0.000 description 64
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 55
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- 238000002844 melting Methods 0.000 description 38
- 230000008018 melting Effects 0.000 description 38
- 238000003756 stirring Methods 0.000 description 37
- 239000000725 suspension Substances 0.000 description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 229960000443 hydrochloric acid Drugs 0.000 description 26
- 235000011167 hydrochloric acid Nutrition 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 20
- 239000012312 sodium hydride Substances 0.000 description 20
- 229910000104 sodium hydride Inorganic materials 0.000 description 20
- 239000007858 starting material Substances 0.000 description 20
- 229940086542 triethylamine Drugs 0.000 description 16
- 239000002480 mineral oil Substances 0.000 description 15
- 235000010446 mineral oil Nutrition 0.000 description 15
- 239000003208 petroleum Substances 0.000 description 13
- 239000002244 precipitate Substances 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- 239000013078 crystal Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 8
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- VONGYFFEWFJHNP-UHFFFAOYSA-N pyrrolecarboxylic acid methyl ester Natural products COC(=O)C1=CC=CN1 VONGYFFEWFJHNP-UHFFFAOYSA-N 0.000 description 6
- 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 5
- 241000700159 Rattus Species 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 150000001340 alkali metals Chemical class 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000003399 chemotactic effect Effects 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 235000015424 sodium Nutrition 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- ILAOVOOZLVGAJF-UHFFFAOYSA-N 1-methylpyrrole-2-carboxylic acid Chemical compound CN1C=CC=C1C(O)=O ILAOVOOZLVGAJF-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
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- MLIREBYILWEBDM-UHFFFAOYSA-N anhydrous cyanoacetic acid Natural products OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 3
- 229940051881 anilide analgesics and antipyretics Drugs 0.000 description 3
- 238000003556 assay Methods 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
- 239000002775 capsule Substances 0.000 description 3
- 230000035605 chemotaxis Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- ZYBWTEQKHIADDQ-UHFFFAOYSA-N ethanol;methanol Chemical compound OC.CCO ZYBWTEQKHIADDQ-UHFFFAOYSA-N 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 229960001614 levamisole Drugs 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- XCTQPMCULSZKLT-UHFFFAOYSA-N 2-cyano-n-phenylacetamide Chemical compound N#CCC(=O)NC1=CC=CC=C1 XCTQPMCULSZKLT-UHFFFAOYSA-N 0.000 description 2
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 239000012670 alkaline solution Substances 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 150000003931 anilides Chemical class 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- GMKILXWDKRXSNM-UHFFFAOYSA-N diethyl 1,3,5-trimethylpyrrole-2,4-dicarboxylate Chemical compound CCOC(=O)C=1C(C)=C(C(=O)OCC)N(C)C=1C GMKILXWDKRXSNM-UHFFFAOYSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- 229940088679 drug related substance Drugs 0.000 description 2
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 150000002513 isocyanates Chemical class 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- HMVKMAMIRAVXAN-UHFFFAOYSA-N 1,3-dichloro-2-isocyanatobenzene Chemical compound ClC1=CC=CC(Cl)=C1N=C=O HMVKMAMIRAVXAN-UHFFFAOYSA-N 0.000 description 1
- HLVFKOKELQSXIQ-UHFFFAOYSA-N 1-bromo-2-methylpropane Chemical compound CC(C)CBr HLVFKOKELQSXIQ-UHFFFAOYSA-N 0.000 description 1
- ADAKRBAJFHTIEW-UHFFFAOYSA-N 1-chloro-4-isocyanatobenzene Chemical compound ClC1=CC=C(N=C=O)C=C1 ADAKRBAJFHTIEW-UHFFFAOYSA-N 0.000 description 1
- FMDGXCSMDZMDHZ-UHFFFAOYSA-N 1-isocyanato-4-methoxybenzene Chemical compound COC1=CC=C(N=C=O)C=C1 FMDGXCSMDZMDHZ-UHFFFAOYSA-N 0.000 description 1
- GFNKTLQTQSALEJ-UHFFFAOYSA-N 1-isocyanato-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(N=C=O)C=C1 GFNKTLQTQSALEJ-UHFFFAOYSA-N 0.000 description 1
- JOYDZQJINHJNPM-UHFFFAOYSA-N 1-methylpyrrole-2-carbonyl chloride Chemical compound CN1C=CC=C1C(Cl)=O JOYDZQJINHJNPM-UHFFFAOYSA-N 0.000 description 1
- 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 1
- IPOVOSHRRIJKBR-UHFFFAOYSA-N 2-ethylpropanedioyl dichloride Chemical compound CCC(C(Cl)=O)C(Cl)=O IPOVOSHRRIJKBR-UHFFFAOYSA-N 0.000 description 1
- HDSRPMNZJOKFPL-UHFFFAOYSA-N 3-(1h-pyrrol-2-yl)propanenitrile Chemical compound N#CCCC1=CC=CN1 HDSRPMNZJOKFPL-UHFFFAOYSA-N 0.000 description 1
- GROUMZKOOYDLTR-UHFFFAOYSA-N 3-(1h-pyrrol-3-yl)propanenitrile Chemical compound N#CCCC=1C=CNC=1 GROUMZKOOYDLTR-UHFFFAOYSA-N 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- ZXGKYNSOZLZWRO-UHFFFAOYSA-N 5-(1-methylpyrrol-2-yl)-n-phenyl-1,2-oxazole-4-carboxamide Chemical compound CN1C=CC=C1C1=C(C(=O)NC=2C=CC=CC=2)C=NO1 ZXGKYNSOZLZWRO-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/337—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members 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
- C07D207/36—Oxygen or sulfur atoms
- C07D207/40—2,5-Pyrrolidine-diones
- C07D207/416—2,5-Pyrrolidine-diones 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 other ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members 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
- C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4606379A | 1979-06-11 | 1979-06-11 | |
| US46,063 | 1979-06-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1133917A true CA1133917A (en) | 1982-10-19 |
Family
ID=21941390
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA353,624A Expired CA1133917A (en) | 1979-06-11 | 1980-06-09 | Alphacarbamoyl-pyrrolpropionitriles, process for their manufacture, pharmaceutical preparations containing these compounds and their therapeutic application |
Country Status (22)
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2127809B (en) * | 1982-09-28 | 1986-03-12 | Ciba Geigy Ag | Certain b-oxo-a-carbamoyl-pyrrolepropionitriles |
| DE3247454A1 (de) * | 1982-12-22 | 1984-06-28 | Laboratorios Bago S.A., Buenos Aires | Substituierte 3-phenyl-5-methyl-isoxazol-4-carboxy-anilide, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DE3525623A1 (de) * | 1985-07-18 | 1987-01-22 | Celamerck Gmbh & Co Kg | Fungizid wirksame acrylsaeureamide |
| GB8619433D0 (en) * | 1986-08-08 | 1986-09-17 | Lilly Industries Ltd | Pharmaceutical compounds |
| GB8619432D0 (en) * | 1986-08-08 | 1986-09-17 | Lilly Industries Ltd | Pharmaceutical compounds |
| JPH02502534A (ja) * | 1987-12-18 | 1990-08-16 | チバ‐ガイギー アクチェンゲゼルシャフト | １‐メチル‐β‐オキソ‐α‐（フェニルカルバモイル）‐２‐ピロールプロピオニトリルのトロメタミン塩 |
| IL92508A0 (en) * | 1988-12-08 | 1990-08-31 | Ciba Geigy Ag | Novel alpha-cyano-beta-oxopropionamides |
| GR880100839A (el) * | 1988-12-15 | 1994-03-31 | Ciba Geigy | Αλας τρομε?αμίνης του 1-με?ύλ-Β-ΟΞΟ-Α-(φαινυλοκαρβομουλό)-2-πυρρολοπροπιονιτριλίου. |
| AU625688B2 (en) * | 1989-01-31 | 1992-07-16 | Merrell Dow Pharmaceuticals Inc. | Method of using aryl- or heteroaryl-1-alkyl-pyrrole-2- carboxylic acid compounds in the treatment of interleukin-1 mediated conditions |
| GB9720899D0 (en) * | 1997-10-01 | 1997-12-03 | Pharmacia & Upjohn Spa | Condensed heterocyclic compounds |
| CN1643587A (zh) * | 2002-03-19 | 2005-07-20 | 拜尔化学品股份公司 | 在光数据载体信息层中作为光吸收化合物的方酸类染料 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE861500C (de) * | 1942-07-05 | 1953-01-05 | Beth Ag Maschf | Spuelluftfilter |
| GB1201061A (en) * | 1966-08-26 | 1970-08-05 | Endo Lab | Oxo pyrroles and process for preparing same |
| 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. | |
| ES448386A1 (es) * | 1975-06-05 | 1978-04-16 | Hoechst Ag | Procedimiento para la preparacion de anilidas de acido 5-me-til-isoxazol-4-carboxilico. |
| DE2654797A1 (de) * | 1976-12-03 | 1978-06-08 | Hoechst Ag | Verfahren zur herstellung von isoxazolderivaten |
-
1980
- 1980-06-09 FI FI801840A patent/FI71129C/fi not_active IP Right Cessation
- 1980-06-09 DD DD80221679A patent/DD151307A5/de not_active IP Right Cessation
- 1980-06-09 AT AT80103180T patent/ATE14724T1/de not_active IP Right Cessation
- 1980-06-09 PT PT71367A patent/PT71367A/pt unknown
- 1980-06-09 EP EP84102678A patent/EP0143142A3/de not_active Withdrawn
- 1980-06-09 IL IL60269A patent/IL60269A/xx unknown
- 1980-06-09 CA CA353,624A patent/CA1133917A/en not_active Expired
- 1980-06-09 GR GR62165A patent/GR69239B/el unknown
- 1980-06-09 EP EP80103180A patent/EP0021207B1/de not_active Expired
- 1980-06-09 DE DE8080103180T patent/DE3070951D1/de not_active Expired
- 1980-06-10 KR KR1019800002269A patent/KR840001131B1/ko not_active Expired
- 1980-06-10 HU HU801461A patent/HU182670B/hu not_active IP Right Cessation
- 1980-06-10 AU AU59173/80A patent/AU539967B2/en not_active Ceased
- 1980-06-10 NO NO801733A patent/NO155197C/no unknown
- 1980-06-10 DK DK250180A patent/DK155996C/da not_active IP Right Cessation
- 1980-06-10 IE IE1185/80A patent/IE50288B1/en not_active IP Right Cessation
- 1980-06-10 ZA ZA00803461A patent/ZA803461B/xx unknown
- 1980-06-10 NZ NZ193995A patent/NZ193995A/xx unknown
- 1980-06-10 ES ES492278A patent/ES492278A0/es active Granted
- 1980-06-11 JP JP7790080A patent/JPS562961A/ja active Granted
-
1984
- 1984-05-29 KR KR1019840002949A patent/KR840001133B1/ko not_active Expired
- 1984-05-29 KR KR1019840002950A patent/KR840001134B1/ko not_active Expired
- 1984-05-29 KR KR1019840002948A patent/KR840001132B1/ko not_active Expired
-
1988
- 1988-01-25 KE KE3795A patent/KE3795A/xx unknown
- 1988-07-07 HK HK502/88A patent/HK50288A/xx unknown
- 1988-09-02 CY CY1426A patent/CY1426A/xx unknown
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| Date | Code | Title | Description |
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| MKEX | Expiry |