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 |
| EP19850116520 EP0187371B1 (en) | 1984-12-27 | 1985-12-23 | Substituted isoquinolinesulfonyl compounds |
| DE8585116520T DE3583287D1 (de) | 1984-12-27 | 1985-12-23 | Substituierte isochinolinsulfonyl-verbindungen. |
| AT85116520T ATE64598T1 (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 (es) | 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 (es) |
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 |
| CA2263425C (en) * | 1996-08-12 | 2008-09-30 | Yoshitomi Pharmaceutical Industries Ltd. | Pharmaceutical agent containing rho kinase inhibitor |
| EP1074545A4 (en) * | 1998-04-23 | 2001-08-22 | Hiroyoshi Hidaka | ISOCHINOLINE SULPHONAMIDE DERIVATIVES AND MEDICINES CONTAINING IT AS AN ACTIVE INGREDIENT |
| JP4260370B2 (ja) * | 1998-08-10 | 2009-04-30 | 旭化成ファーマ株式会社 | 塩酸ファスジルの経口徐放性製剤 |
| 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 |
| WO2005073218A1 (ja) * | 2004-01-29 | 2005-08-11 | Asahi Kasei Pharma Corporation | バイパス術に伴う血管攣縮治療剤 |
| KR101194123B1 (ko) | 2004-03-16 | 2012-10-24 | 아사히 가세이 파마 가부시키가이샤 | 패수딜 함유 제제 및 그 안정성을 개선하는 방법 |
| JP4257383B2 (ja) | 2005-04-25 | 2009-04-22 | 株式会社デ・ウエスタン・セラピテクス研究所 | 高選択的Ｒｈｏキナーゼ阻害剤 |
| WO2007007737A1 (ja) | 2005-07-12 | 2007-01-18 | Kowa Co., Ltd. | 緑内障を予防又は治療する薬剤 |
| US8283337B2 (en) | 2007-02-23 | 2012-10-09 | Next21 K.K. | Therapeutic or prophylactic agent for vasoconstriction |
| EP2818463A1 (en) | 2010-08-26 | 2014-12-31 | Kowa Co., Ltd. | Production method of 1,4-diazepane derivatives |
| CN111132983B (zh) * | 2017-09-25 | 2022-05-17 | 华润医药控股有限公司 | 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 (en) * | 1982-11-18 | 1984-05-23 | Asahi Kasei Kogyo Kabushiki Kaisha | Isoquinolinesulfonamide derivatives and process for the preparation thereof |
-
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 (en) * | 1982-11-18 | 1984-05-23 | Asahi Kasei Kogyo Kabushiki Kaisha | Isoquinolinesulfonamide derivatives and process for the preparation thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61227581A (ja) | 1986-10-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EXPY | Cancellation because of completion of term |