CA2198266C - Derives nouveaux de benzimidazole - Google Patents
Derives nouveaux de benzimidazole Download PDFInfo
- Publication number
- CA2198266C CA2198266C CA002198266A CA2198266A CA2198266C CA 2198266 C CA2198266 C CA 2198266C CA 002198266 A CA002198266 A CA 002198266A CA 2198266 A CA2198266 A CA 2198266A CA 2198266 C CA2198266 C CA 2198266C
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- Canada
- Prior art keywords
- group
- substituted
- formula
- alkyl group
- alkyl
- Prior art date
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- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title claims description 3
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title abstract description 21
- -1 3,4dihydro-2(1H)-quinolinonyl group Chemical group 0.000 claims abstract description 323
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 74
- 150000003839 salts Chemical class 0.000 claims abstract description 66
- 150000001556 benzimidazoles Chemical class 0.000 claims abstract description 62
- 125000005843 halogen group Chemical group 0.000 claims abstract description 52
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 38
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims abstract description 14
- 125000001041 indolyl group Chemical group 0.000 claims abstract description 14
- 125000005955 1H-indazolyl group Chemical group 0.000 claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims description 265
- 239000002904 solvent Substances 0.000 claims description 104
- 125000001424 substituent group Chemical group 0.000 claims description 86
- 230000002401 inhibitory effect Effects 0.000 claims description 41
- 239000000203 mixture Substances 0.000 claims description 40
- 150000001412 amines Chemical class 0.000 claims description 38
- 230000035755 proliferation Effects 0.000 claims description 30
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 29
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000003277 amino group Chemical group 0.000 claims description 21
- 229920006395 saturated elastomer Polymers 0.000 claims description 20
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 16
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims description 12
- 230000002255 enzymatic effect Effects 0.000 claims description 10
- 125000004043 oxo group Chemical group O=* 0.000 claims description 10
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000004434 sulfur atom Chemical group 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 102000008186 Collagen Human genes 0.000 claims description 5
- 108010035532 Collagen Proteins 0.000 claims description 5
- 229920001436 collagen Polymers 0.000 claims description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 230000028327 secretion Effects 0.000 claims description 5
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- 230000007062 hydrolysis Effects 0.000 claims description 4
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical group C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 3
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 3
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 2
- TZOYXRMEFDYWDQ-UHFFFAOYSA-N 3,4-dihydro-1h-quinolin-2-one Chemical group C1=CC=C2NC(=O)CCC2=C1 TZOYXRMEFDYWDQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000001819 4H-chromenyl group Chemical group O1C(=CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000005946 imidazo[1,2-a]pyridyl group Chemical group 0.000 claims description 2
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 2
- 230000001506 immunosuppresive effect Effects 0.000 claims description 2
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 2
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000005543 phthalimide group Chemical group 0.000 claims description 2
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 2
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 87
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 18
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 12
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 8
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 7
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 7
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- KMLKVKBMXYSALS-UHFFFAOYSA-N 1-benzyl-6-chloro-n-[1-(3-imidazol-1-ylpropyl)indol-5-yl]benzimidazole-2-carboxamide Chemical compound C=1C=CC=CC=1CN1C2=CC(Cl)=CC=C2N=C1C(=O)NC(C=C1C=C2)=CC=C1N2CCCN1C=CN=C1 KMLKVKBMXYSALS-UHFFFAOYSA-N 0.000 claims 1
- LKEFOCJVSAVQLM-UHFFFAOYSA-N 1-benzyl-6-chloro-n-[1-(3-pyrazol-1-ylpropyl)indol-5-yl]benzimidazole-2-carboxamide Chemical compound C=1C=CC=CC=1CN1C2=CC(Cl)=CC=C2N=C1C(=O)NC(C=C1C=C2)=CC=C1N2CCCN1C=CC=N1 LKEFOCJVSAVQLM-UHFFFAOYSA-N 0.000 claims 1
- GLRAXZSBUGHTHZ-UHFFFAOYSA-N 1-benzyl-6-chloro-n-[1-[3-(1,2,4-triazol-1-yl)propyl]indol-5-yl]benzimidazole-2-carboxamide Chemical compound C=1C=CC=CC=1CN1C2=CC(Cl)=CC=C2N=C1C(=O)NC(C=C1C=C2)=CC=C1N2CCCN1C=NC=N1 GLRAXZSBUGHTHZ-UHFFFAOYSA-N 0.000 claims 1
- PJNWEKCTGWNRLU-UHFFFAOYSA-N 1-benzyl-6-chloro-n-[1-[3-(4-hydroxy-4-phenylpiperidin-1-yl)propyl]indol-5-yl]benzimidazole-2-carboxamide Chemical compound C1CC(O)(C=2C=CC=CC=2)CCN1CCCN(C1=CC=2)C=CC1=CC=2NC(=O)C1=NC2=CC=C(Cl)C=C2N1CC1=CC=CC=C1 PJNWEKCTGWNRLU-UHFFFAOYSA-N 0.000 claims 1
- AOLQHCDZEAGLLA-UHFFFAOYSA-N 1-benzyl-6-chloro-n-[1-[3-[cyclohexyl(methyl)amino]propyl]indol-5-yl]benzimidazole-2-carboxamide Chemical compound C1CCCCC1N(C)CCCN(C1=CC=2)C=CC1=CC=2NC(=O)C1=NC2=CC=C(Cl)C=C2N1CC1=CC=CC=C1 AOLQHCDZEAGLLA-UHFFFAOYSA-N 0.000 claims 1
- YTVKRZNLBRAFTF-UHFFFAOYSA-N 1-benzyl-6-chloro-n-[4-[3-(pyridine-2-carbonylamino)propyl]-2,3-dihydro-1,4-benzoxazin-7-yl]benzimidazole-2-carboxamide Chemical compound C=1C=CC=CC=1CN1C2=CC(Cl)=CC=C2N=C1C(=O)NC(C=C1OCC2)=CC=C1N2CCCNC(=O)C1=CC=CC=N1 YTVKRZNLBRAFTF-UHFFFAOYSA-N 0.000 claims 1
- 125000002541 furyl group Chemical group 0.000 claims 1
- YPMMOZSZWWEJLF-UHFFFAOYSA-N n-[3-[5-[(1-benzyl-6-chlorobenzimidazole-2-carbonyl)amino]indol-1-yl]propyl]-3,5-dimethyl-1,2-oxazole-4-carboxamide Chemical compound CC1=NOC(C)=C1C(=O)NCCCN1C2=CC=C(NC(=O)C=3N(C4=CC(Cl)=CC=C4N=3)CC=3C=CC=CC=3)C=C2C=C1 YPMMOZSZWWEJLF-UHFFFAOYSA-N 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 73
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 abstract description 29
- 239000003795 chemical substances by application Substances 0.000 abstract description 22
- 201000010099 disease Diseases 0.000 abstract description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 13
- 125000002947 alkylene group Chemical group 0.000 abstract description 5
- 238000006243 chemical reaction Methods 0.000 description 158
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 83
- 239000013078 crystal Substances 0.000 description 71
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- 238000000034 method Methods 0.000 description 54
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 52
- 239000000047 product Substances 0.000 description 49
- 238000002844 melting Methods 0.000 description 48
- 230000008018 melting Effects 0.000 description 48
- 235000019441 ethanol Nutrition 0.000 description 47
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 43
- 101150041968 CDC13 gene Proteins 0.000 description 41
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 41
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 41
- 238000005160 1H NMR spectroscopy Methods 0.000 description 40
- 230000000694 effects Effects 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- 238000001953 recrystallisation Methods 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 34
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 32
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 31
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 26
- 238000012360 testing method Methods 0.000 description 26
- 238000005481 NMR spectroscopy Methods 0.000 description 25
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- 239000003638 chemical reducing agent Substances 0.000 description 24
- 239000000243 solution Substances 0.000 description 23
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 22
- 239000000825 pharmaceutical preparation Substances 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000002253 acid Substances 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
- 239000003826 tablet Substances 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 18
- 150000002148 esters Chemical class 0.000 description 17
- 239000007858 starting material Substances 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 150000007514 bases Chemical class 0.000 description 16
- 125000004432 carbon atom Chemical group C* 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 229960001701 chloroform Drugs 0.000 description 15
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
- 238000004821 distillation Methods 0.000 description 14
- 150000002170 ethers Chemical class 0.000 description 14
- 150000001298 alcohols Chemical class 0.000 description 13
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 13
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 125000003342 alkenyl group Chemical group 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- 239000008187 granular material Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 210000000624 ear auricle Anatomy 0.000 description 10
- 150000002367 halogens Chemical group 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 9
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 9
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 9
- 235000019253 formic acid Nutrition 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
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- 125000001309 chloro group Chemical group Cl* 0.000 description 8
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- 150000004678 hydrides Chemical class 0.000 description 8
- 229910052751 metal Inorganic materials 0.000 description 8
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
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- 238000011282 treatment Methods 0.000 description 8
- 201000004624 Dermatitis Diseases 0.000 description 7
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 7
- 125000003545 alkoxy group Chemical group 0.000 description 7
- 239000000969 carrier Substances 0.000 description 7
- 229960000443 hydrochloric acid Drugs 0.000 description 7
- 235000011167 hydrochloric acid Nutrition 0.000 description 7
- 239000012280 lithium aluminium hydride Substances 0.000 description 7
- 210000003584 mesangial cell Anatomy 0.000 description 7
- 238000000926 separation method Methods 0.000 description 7
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- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- 239000008107 starch Substances 0.000 description 7
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Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Nouveaux dérivés de benzimidazole ou sels desdits dérivés, de formule générale (1) dans laquelle R<1> est un atome d'hydrogène ou un atome d'halogène, R<2> est un groupe phényle-alkyle inférieur, R<3> est un groupe hétérocyclique choisi dans le groupe constitué d'un groupe indolyle, d'un groupe indolinyle, d'un groupe 1H-indazolyle, d'un groupe 2(1H)-quinolinonyle, d'un groupe 3,4-dihydro-2(1H)-quinolinonyle et d'un groupe 1,4-benzoxazinyle, A est un groupe alkylène inférieur, n est 0 ou 1. Lesdits dérivés de benzimidazole ou sels de la présente invention sont des agents efficaces pour traiter diverses maladies artérioscléreuses.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7/171807 | 1995-07-07 | ||
| JP17180795 | 1995-07-07 | ||
| PCT/JP1996/001841 WO1997003070A1 (fr) | 1995-07-07 | 1996-07-03 | Nouveaux derives de benzimidazole ayant une activite d'inhibition de la cgmp-phosphodisterase |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2198266A1 CA2198266A1 (fr) | 1997-01-30 |
| CA2198266C true CA2198266C (fr) | 2006-04-04 |
Family
ID=36143252
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002198266A Expired - Fee Related CA2198266C (fr) | 1995-07-07 | 1996-07-03 | Derives nouveaux de benzimidazole |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2198266C (fr) |
-
1996
- 1996-07-03 CA CA002198266A patent/CA2198266C/fr not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2198266A1 (fr) | 1997-01-30 |
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| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |