JPH053851B2 - - Google Patents
Info
- Publication number
- JPH053851B2 JPH053851B2 JP60068512A JP6851285A JPH053851B2 JP H053851 B2 JPH053851 B2 JP H053851B2 JP 60068512 A JP60068512 A JP 60068512A JP 6851285 A JP6851285 A JP 6851285A JP H053851 B2 JPH053851 B2 JP H053851B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- isoquinolinesulfonyl
- acid
- homopiperazine
- methylhomopiperazine
- 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 - Lifetime
Links
- 239000002253 acid Substances 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 229940124549 vasodilator Drugs 0.000 claims description 4
- 239000003071 vasodilator agent Substances 0.000 claims description 4
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 150000001875 compounds Chemical class 0.000 description 17
- 239000000243 solution Substances 0.000 description 14
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- -1 2-ethyl homopiperazine Chemical compound 0.000 description 8
- 230000017531 blood circulation Effects 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000000370 acceptor Substances 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- NGOGFTYYXHNFQH-UHFFFAOYSA-N fasudil Chemical compound C=1C=CC2=CN=CC=C2C=1S(=O)(=O)N1CCCNCC1 NGOGFTYYXHNFQH-UHFFFAOYSA-N 0.000 description 5
- 210000001105 femoral artery Anatomy 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 230000002040 relaxant effect Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 210000002385 vertebral artery Anatomy 0.000 description 5
- FOHHXQVBNAWSRY-UHFFFAOYSA-N 5-[(6-benzyl-1,4-diazepan-1-yl)sulfonyl]isoquinoline Chemical compound C=1C=CC2=CN=CC=C2C=1S(=O)(=O)N(C1)CCNCC1CC1=CC=CC=C1 FOHHXQVBNAWSRY-UHFFFAOYSA-N 0.000 description 4
- MYAPYEAJIBZZJX-UHFFFAOYSA-N 5-[(6-methyl-1,4-diazepan-1-yl)sulfonyl]isoquinoline Chemical compound C1C(C)CNCCN1S(=O)(=O)C1=CC=CC2=CN=CC=C12 MYAPYEAJIBZZJX-UHFFFAOYSA-N 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 3
- CUCODOZMSCSEPM-UHFFFAOYSA-N 5-[(3-phenyl-1,4-diazepan-1-yl)sulfonyl]isoquinoline Chemical compound C=1C=CC2=CN=CC=C2C=1S(=O)(=O)N(C1)CCCNC1C1=CC=CC=C1 CUCODOZMSCSEPM-UHFFFAOYSA-N 0.000 description 3
- HMFOONDXHLLTKQ-UHFFFAOYSA-N 5-[(6-hexyl-1,4-diazepan-1-yl)sulfonyl]isoquinoline Chemical compound C1C(CCCCCC)CNCCN1S(=O)(=O)C1=CC=CC2=CN=CC=C12 HMFOONDXHLLTKQ-UHFFFAOYSA-N 0.000 description 3
- VHJDJLJQIUIBDM-UHFFFAOYSA-N 5-[(6-propyl-1,4-diazepan-1-yl)sulfonyl]isoquinoline Chemical compound C1C(CCC)CNCCN1S(=O)(=O)C1=CC=CC2=CN=CC=C12 VHJDJLJQIUIBDM-UHFFFAOYSA-N 0.000 description 3
- FXMGNOMVHROLBO-UHFFFAOYSA-N 5-[[3-(2-methylpropyl)-1,4-diazepan-1-yl]sulfonyl]isoquinoline Chemical compound C1CCNC(CC(C)C)CN1S(=O)(=O)C1=CC=CC2=CN=CC=C12 FXMGNOMVHROLBO-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000008602 contraction Effects 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 150000004050 homopiperazines Chemical class 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- GZQNTWHQJJVIAK-UHFFFAOYSA-N isoquinoline-5-sulfonyl chloride;hydrochloride Chemical compound Cl.N1=CC=C2C(S(=O)(=O)Cl)=CC=CC2=C1 GZQNTWHQJJVIAK-UHFFFAOYSA-N 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 210000001363 mesenteric artery superior Anatomy 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000001103 potassium chloride Substances 0.000 description 3
- 235000011164 potassium chloride Nutrition 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- UIJOYUWVUOLWGZ-UHFFFAOYSA-N 5-[(3-benzyl-1,4-diazepan-1-yl)sulfonyl]isoquinoline Chemical compound C=1C=CC2=CN=CC=C2C=1S(=O)(=O)N(C1)CCCNC1CC1=CC=CC=C1 UIJOYUWVUOLWGZ-UHFFFAOYSA-N 0.000 description 2
- PDDYZDBYVDJCNL-UHFFFAOYSA-N 5-[(3-methyl-1,4-diazepan-1-yl)sulfonyl]isoquinoline Chemical compound C1CCNC(C)CN1S(=O)(=O)C1=CC=CC2=CN=CC=C12 PDDYZDBYVDJCNL-UHFFFAOYSA-N 0.000 description 2
- ZORUZQHLSMGYFV-UHFFFAOYSA-N 5-[(6-butyl-1,4-diazepan-1-yl)sulfonyl]isoquinoline Chemical compound C1C(CCCC)CNCCN1S(=O)(=O)C1=CC=CC2=CN=CC=C12 ZORUZQHLSMGYFV-UHFFFAOYSA-N 0.000 description 2
- ZKWABTWQSZMPDK-UHFFFAOYSA-N 5-[(6-pentyl-1,4-diazepan-1-yl)sulfonyl]isoquinoline Chemical compound C1C(CCCCC)CNCCN1S(=O)(=O)C1=CC=CC2=CN=CC=C12 ZKWABTWQSZMPDK-UHFFFAOYSA-N 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 241000283977 Oryctolagus Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- JOINYCKVHXRGDV-UHFFFAOYSA-N benzyl 3-methyl-1,4-diazepane-1-carboxylate Chemical compound C1CCNC(C)CN1C(=O)OCC1=CC=CC=C1 JOINYCKVHXRGDV-UHFFFAOYSA-N 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- YFMJTLUPSMCTOQ-UHFFFAOYSA-N isoquinoline-5-sulfonic acid Chemical compound N1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 YFMJTLUPSMCTOQ-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 210000002464 muscle smooth vascular Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- YQWYNMOCRRYVCE-UHFFFAOYSA-N 1,4-dimethyl-1,4-diazepane Chemical compound CN1CCCN(C)CC1 YQWYNMOCRRYVCE-UHFFFAOYSA-N 0.000 description 1
- NGECKXKOOXAGCQ-UHFFFAOYSA-N 1-benzyl-3-methyl-1,4-diazepane Chemical compound C1CCNC(C)CN1CC1=CC=CC=C1 NGECKXKOOXAGCQ-UHFFFAOYSA-N 0.000 description 1
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 1
- BCPHESVFXXEVHA-UHFFFAOYSA-N 2,2-dimethyl-1,4-diazepane Chemical compound CC1(C)CNCCCN1 BCPHESVFXXEVHA-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical group CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- SVMWMAWMDBDDIM-UHFFFAOYSA-N 2-benzyl-1,4-diazepane Chemical compound C=1C=CC=CC=1CC1CNCCCN1 SVMWMAWMDBDDIM-UHFFFAOYSA-N 0.000 description 1
- PQOLMVXRIQLMNF-UHFFFAOYSA-N 2-phenyl-1,4-diazepane Chemical compound N1CCCNCC1C1=CC=CC=C1 PQOLMVXRIQLMNF-UHFFFAOYSA-N 0.000 description 1
- KBRAFCMQLHSOQL-UHFFFAOYSA-N 5,7-dimethyl-1,4-diazepane Chemical compound CC1CC(C)NCCN1 KBRAFCMQLHSOQL-UHFFFAOYSA-N 0.000 description 1
- SBNQPUSUBMHWKQ-UHFFFAOYSA-N 5-[(2,3-dimethyl-1,4-diazepan-1-yl)sulfonyl]isoquinoline Chemical compound CC1C(C)NCCCN1S(=O)(=O)C1=CC=CC2=CN=CC=C12 SBNQPUSUBMHWKQ-UHFFFAOYSA-N 0.000 description 1
- DSOQHHGSXZTTAQ-UHFFFAOYSA-N 5-[(2-methyl-1,4-diazepan-1-yl)sulfonyl]isoquinoline Chemical compound CC1CNCCCN1S(=O)(=O)C1=CC=CC2=CN=CC=C12 DSOQHHGSXZTTAQ-UHFFFAOYSA-N 0.000 description 1
- ZNCQFVSAEWMXEH-UHFFFAOYSA-N 5-[(3,3-dimethyl-1,4-diazepan-1-yl)sulfonyl]isoquinoline Chemical compound C1CCNC(C)(C)CN1S(=O)(=O)C1=CC=CC2=CN=CC=C12 ZNCQFVSAEWMXEH-UHFFFAOYSA-N 0.000 description 1
- XPZIPBHGKYENEW-UHFFFAOYSA-N 5-[(3-ethyl-1,4-diazepan-1-yl)sulfonyl]isoquinoline Chemical compound C1CCNC(CC)CN1S(=O)(=O)C1=CC=CC2=CN=CC=C12 XPZIPBHGKYENEW-UHFFFAOYSA-N 0.000 description 1
- ZAVGOWDXUKLLDG-UHFFFAOYSA-N 5-[(6-ethyl-1,4-diazepan-1-yl)sulfonyl]isoquinoline Chemical compound C1C(CC)CNCCN1S(=O)(=O)C1=CC=CC2=CN=CC=C12 ZAVGOWDXUKLLDG-UHFFFAOYSA-N 0.000 description 1
- ACXJJHSDUAJXCI-UHFFFAOYSA-N 5-[(6-phenyl-1,4-diazepan-1-yl)sulfonyl]isoquinoline Chemical compound C=1C=CC2=CN=CC=C2C=1S(=O)(=O)N(C1)CCNCC1C1=CC=CC=C1 ACXJJHSDUAJXCI-UHFFFAOYSA-N 0.000 description 1
- ASSSRDKELRPUBU-UHFFFAOYSA-N 5-ethyl-1,4-diazepane Chemical compound CCC1CCNCCN1 ASSSRDKELRPUBU-UHFFFAOYSA-N 0.000 description 1
- PCSCFJLGJHWKJL-UHFFFAOYSA-N 5-methyl-1,4-diazepane Chemical compound CC1CCNCCN1 PCSCFJLGJHWKJL-UHFFFAOYSA-N 0.000 description 1
- HTFBFCBNOJSGCN-UHFFFAOYSA-N 6-benzyl-1,4-diazepane Chemical compound C=1C=CC=CC=1CC1CNCCNC1 HTFBFCBNOJSGCN-UHFFFAOYSA-N 0.000 description 1
- WKZZHWMGFNCQRG-UHFFFAOYSA-N 6-butyl-1,4-diazepane Chemical compound CCCCC1CNCCNC1 WKZZHWMGFNCQRG-UHFFFAOYSA-N 0.000 description 1
- RWGWOOIFJQGCOX-UHFFFAOYSA-N 6-ethyl-1,4-diazepane Chemical compound CCC1CNCCNC1 RWGWOOIFJQGCOX-UHFFFAOYSA-N 0.000 description 1
- BJGANCARKGYUEU-UHFFFAOYSA-N 6-hexyl-1,4-diazepane Chemical compound CCCCCCC1CNCCNC1 BJGANCARKGYUEU-UHFFFAOYSA-N 0.000 description 1
- VMJOIXFVKVPLRQ-UHFFFAOYSA-N 6-methyl-1,4-diazepane Chemical compound CC1CNCCNC1 VMJOIXFVKVPLRQ-UHFFFAOYSA-N 0.000 description 1
- XAUFKSXCSWRZJQ-UHFFFAOYSA-N 6-phenyl-1,4-diazepane Chemical compound C1NCCNCC1C1=CC=CC=C1 XAUFKSXCSWRZJQ-UHFFFAOYSA-N 0.000 description 1
- KWEYWXIDSIKQCZ-UHFFFAOYSA-N 6-propyl-1,4-diazepane Chemical compound CCCC1CNCCNC1 KWEYWXIDSIKQCZ-UHFFFAOYSA-N 0.000 description 1
- LZKIDRNIHSEQGN-UHFFFAOYSA-N C1CNC(CCC)CN1C(=O)OCC1=CC=CC=C1 Chemical compound C1CNC(CCC)CN1C(=O)OCC1=CC=CC=C1 LZKIDRNIHSEQGN-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- MNZMECMQTYGSOI-UHFFFAOYSA-N acetic acid;hydron;bromide Chemical compound Br.CC(O)=O MNZMECMQTYGSOI-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000001339 alkali metal compounds Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000004531 blood pressure lowering effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- LFVPBERIVUNMGV-UHFFFAOYSA-N fasudil hydrochloride Chemical compound Cl.C=1C=CC2=CN=CC=C2C=1S(=O)(=O)N1CCCNCC1 LFVPBERIVUNMGV-UHFFFAOYSA-N 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- WHIDHHUCCTYJKA-UHFFFAOYSA-N isoquinoline-5-sulfonyl chloride Chemical compound N1=CC=C2C(S(=O)(=O)Cl)=CC=CC2=C1 WHIDHHUCCTYJKA-UHFFFAOYSA-N 0.000 description 1
- 150000002537 isoquinolines Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- GDTFCUXOVITPHU-UHFFFAOYSA-N tert-butyl 3-methyl-1,4-diazepane-1-carboxylate Chemical compound CC1CN(C(=O)OC(C)(C)C)CCCN1 GDTFCUXOVITPHU-UHFFFAOYSA-N 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
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6851285A JPS61227581A (ja) | 1985-04-02 | 1985-04-02 | 血管拡張剤 |
| DE8585116520T DE3583287D1 (de) | 1984-12-27 | 1985-12-23 | Substituierte isochinolinsulfonyl-verbindungen. |
| AT85116520T ATE64598T1 (de) | 1984-12-27 | 1985-12-23 | Substituierte isochinolinsulfonyl-verbindungen. |
| EP19850116520 EP0187371B1 (de) | 1984-12-27 | 1985-12-23 | Substituierte Isochinolinsulfonyl-Verbindungen |
| US06813973 US4678783B1 (en) | 1983-11-04 | 1985-12-27 | Substituted isoquinolinesulfonyl compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6851285A JPS61227581A (ja) | 1985-04-02 | 1985-04-02 | 血管拡張剤 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61227581A JPS61227581A (ja) | 1986-10-09 |
| JPH053851B2 true JPH053851B2 (de) | 1993-01-18 |
Family
ID=13375841
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6851285A Granted JPS61227581A (ja) | 1983-11-04 | 1985-04-02 | 血管拡張剤 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61227581A (de) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0667926B2 (ja) * | 1985-11-12 | 1994-08-31 | 旭化成工業株式会社 | 環状のイソキノリンスルホンアミド誘導体 |
| JP2720348B2 (ja) * | 1989-03-30 | 1998-03-04 | 旭化成工業株式会社 | 脳細胞機能障害改善剤 |
| JP2893029B2 (ja) * | 1992-08-10 | 1999-05-17 | 旭化成工業株式会社 | 心臓保護剤 |
| JPH0680569A (ja) * | 1992-09-03 | 1994-03-22 | Asahi Chem Ind Co Ltd | 血小板凝集阻害剤 |
| JP3834663B2 (ja) * | 1996-02-02 | 2006-10-18 | 株式会社デ・ウエスタン・セラピテクス研究所 | イソキノリン誘導体及び医薬 |
| ATE359822T1 (de) * | 1996-08-12 | 2007-05-15 | Mitsubishi Pharma Corp | Medikamente enthaltend rho-kinase inhibitoren |
| CA2327276A1 (en) * | 1998-04-23 | 1999-10-28 | Hiroshi Muramatsu | Isoquinolinesulfonamide derivatives and drugs containing the same as the active ingredient |
| CN100444843C (zh) * | 1998-08-10 | 2008-12-24 | 旭化成制药株式会社 | 法舒地尔盐酸盐缓释口服制剂 |
| CA2369560C (en) | 1999-04-27 | 2011-02-01 | Makoto Nakamuta | Agent for prophylaxis and treatment of liver disease |
| JP4582561B2 (ja) * | 2000-10-23 | 2010-11-17 | 旭化成ファーマ株式会社 | 移植による血管病変の発生抑制剤 |
| JP4854070B2 (ja) * | 2004-01-29 | 2012-01-11 | 旭化成ファーマ株式会社 | バイパス術に伴う血管攣縮治療剤 |
| CA2559630C (en) | 2004-03-16 | 2012-04-17 | Asahi Kasei Pharma Corporation | Fasudil-containing preparation and method of improving stability thereof |
| WO2006115247A1 (ja) | 2005-04-25 | 2006-11-02 | D. Western Therapeutics Institute, Inc. | 高選択的Ｒｈｏキナーゼ阻害剤 |
| KR101333990B1 (ko) | 2005-07-12 | 2013-11-27 | 코와 가부시키가이샤 | 녹내장을 예방 또는 치료하는 약제 |
| JP5781727B2 (ja) | 2007-02-23 | 2015-09-24 | 株式会社ネクスト２１ | 血管攣縮の治療剤又は予防剤 |
| JP5858917B2 (ja) * | 2010-08-26 | 2016-02-10 | 興和株式会社 | イソキノリン誘導体又はその塩の新規製造方法 |
| WO2019057121A1 (zh) * | 2017-09-25 | 2019-03-28 | 南京明德新药研发股份有限公司 | 一种异喹啉磺酰衍生物的晶型及其制备方法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS57200366A (en) * | 1981-06-01 | 1982-12-08 | Asahi Chem Ind Co Ltd | Isoquinoline compound |
| JPS58121279A (ja) * | 1982-01-14 | 1983-07-19 | Asahi Chem Ind Co Ltd | イソキノリンスルホニル化合物 |
| EP0109023A1 (de) * | 1982-11-18 | 1984-05-23 | Asahi Kasei Kogyo Kabushiki Kaisha | Isochinolin-sulfonamidderivate und Verfahren für ihre Herstellung |
-
1985
- 1985-04-02 JP JP6851285A patent/JPS61227581A/ja active Granted
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS57200366A (en) * | 1981-06-01 | 1982-12-08 | Asahi Chem Ind Co Ltd | Isoquinoline compound |
| JPS58121279A (ja) * | 1982-01-14 | 1983-07-19 | Asahi Chem Ind Co Ltd | イソキノリンスルホニル化合物 |
| EP0109023A1 (de) * | 1982-11-18 | 1984-05-23 | Asahi Kasei Kogyo Kabushiki Kaisha | Isochinolin-sulfonamidderivate und Verfahren für ihre Herstellung |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61227581A (ja) | 1986-10-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH053851B2 (de) | ||
| JP5405314B2 (ja) | シクロアルキルアミン置換イソキノロン誘導体 | |
| JP5318779B2 (ja) | シクロアルキルアミン置換イソキノリン及びイソキノリノン誘導体 | |
| JP5405316B2 (ja) | シクロアルキルアミン置換イソキノリン誘導体 | |
| JP5318778B2 (ja) | シクロアルキルアミン置換イソキノロン及びイソキノリノン誘導体 | |
| JP2898139B2 (ja) | 環状ジアミン化合物及びその中間体 | |
| JPH0428698B2 (de) | ||
| JPS62111981A (ja) | 環状のイソキノリンスルホンアミド誘導体 | |
| HUT74579A (en) | New ginkgolide derivatives, process for preparing them and pharmaceutical composition containing them | |
| KR100264807B1 (ko) | 혈관내막비후억제제 | |
| HU214871B (hu) | Eljárás pirazol-piridin-származékok előállítására | |
| BG66240B1 (bg) | Аминоалкилбензоил - бензофурани или бензотиофени, метод за получаването им и състави, които ги съдържат | |
| HU218487B (hu) | N-Ciano-piridin-karboximid-amid-származékok, ilyen vegyületeket tartalmazó gyógyászati készítmények és eljárás a vegyületek előállítására | |
| EP0597112A1 (de) | Neue imidazolderivate, ihre pharmazeutische verwendung und ihre intermediate | |
| EP0326106A2 (de) | Alkylen-diamine | |
| JPH062741B2 (ja) | ２級のイソキノリンスルホンアミド誘導体 | |
| JPS6361942B2 (de) | ||
| JPH0481986B2 (de) | ||
| JP3140155B2 (ja) | Ｎ，ｎ’−ジ置換アミド誘導体 | |
| JP2980749B2 (ja) | フラン誘導体 | |
| JPH069565A (ja) | イソキノリンスルホン酸アミド化合物 | |
| JPH0227992B2 (ja) | Isokinorinsuruhonirukagobutsu | |
| JP3269658B2 (ja) | フェノール誘導体 | |
| JPH0742276B2 (ja) | 新規ｎ置換３，４―ジヒドロピリミジン誘導体および血管拡張剤 | |
| JPS6130677B2 (de) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EXPY | Cancellation because of completion of term |