JPS6342622B2 - - Google Patents
Info
- Publication number
- JPS6342622B2 JPS6342622B2 JP55083844A JP8384480A JPS6342622B2 JP S6342622 B2 JPS6342622 B2 JP S6342622B2 JP 55083844 A JP55083844 A JP 55083844A JP 8384480 A JP8384480 A JP 8384480A JP S6342622 B2 JPS6342622 B2 JP S6342622B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- thiazole
- yield
- benzo
- tetrahydro
- 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 claims description 59
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 22
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- 150000001412 amines Chemical class 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 4
- -1 lithium aluminum hydride Chemical compound 0.000 claims description 4
- GOBQGMKTJNILRX-UHFFFAOYSA-N 1-(2-butyl-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl)-n-methylmethanamine Chemical compound CNCC1CCCC2=C1N=C(CCCC)S2 GOBQGMKTJNILRX-UHFFFAOYSA-N 0.000 claims description 3
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 claims description 3
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 3
- OFSPYMGCSOTXQN-UHFFFAOYSA-N n-methyl-1-(2-methyl-4,5,6,7-tetrahydro-1,3-benzothiazol-5-yl)methanamine Chemical compound C1C(CNC)CCC2=C1N=C(C)S2 OFSPYMGCSOTXQN-UHFFFAOYSA-N 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- 238000000034 method Methods 0.000 description 19
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 241000282472 Canis lupus familiaris Species 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 230000017531 blood circulation Effects 0.000 description 6
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 210000001367 artery Anatomy 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- VKCMWLOBUILIOQ-UHFFFAOYSA-N ethyl 3-bromo-2-oxocyclohexane-1-carboxylate Chemical compound CCOC(=O)C1CCCC(Br)C1=O VKCMWLOBUILIOQ-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- UHGULLIUJBCTEF-UHFFFAOYSA-N 2-aminobenzothiazole Chemical class C1=CC=C2SC(N)=NC2=C1 UHGULLIUJBCTEF-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 210000000748 cardiovascular system Anatomy 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 210000001105 femoral artery Anatomy 0.000 description 3
- CYEBJEDOHLIWNP-UHFFFAOYSA-N methanethioamide Chemical compound NC=S CYEBJEDOHLIWNP-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 3
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 3
- 150000003556 thioamides Chemical class 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- MUMCMYYMLIPEGV-UHFFFAOYSA-N (2-methyl-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl)methanamine Chemical compound NCC1CCCC2=C1N=C(C)S2 MUMCMYYMLIPEGV-UHFFFAOYSA-N 0.000 description 2
- UKIGHVSLNMIODZ-UHFFFAOYSA-N 1-(2-butyl-4,5,6,7-tetrahydro-1,3-benzothiazol-5-yl)-n-methylmethanamine Chemical compound C1C(CNC)CCC2=C1N=C(CCCC)S2 UKIGHVSLNMIODZ-UHFFFAOYSA-N 0.000 description 2
- HALOWOFMAIDLKM-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1,3-benzothiazol-4-ylmethanamine Chemical compound NCC1CCCC2=C1N=CS2 HALOWOFMAIDLKM-UHFFFAOYSA-N 0.000 description 2
- KZMOYPDEKDQCQQ-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1,3-benzothiazol-6-ylmethanamine Chemical compound C1C(CN)CCC2=C1SC=N2 KZMOYPDEKDQCQQ-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- OJYGBLRPYBAHRT-IPQSZEQASA-N chloralose Chemical compound O1[C@H](C(Cl)(Cl)Cl)O[C@@H]2[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]21 OJYGBLRPYBAHRT-IPQSZEQASA-N 0.000 description 2
- 229950009941 chloralose Drugs 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- IGOWSOGBQMBHIY-UHFFFAOYSA-N ethyl 3-bromo-4-oxocyclohexane-1-carboxylate Chemical compound CCOC(=O)C1CCC(=O)C(Br)C1 IGOWSOGBQMBHIY-UHFFFAOYSA-N 0.000 description 2
- PTBQJQQHFAEVAU-UHFFFAOYSA-N ethyl 4,5,6,7-tetrahydro-1,3-benzothiazole-6-carboxylate Chemical compound C1C(C(=O)OCC)CCC2=C1SC=N2 PTBQJQQHFAEVAU-UHFFFAOYSA-N 0.000 description 2
- UDLLBXAEMDYVSW-UHFFFAOYSA-N ethyl 4-bromo-3-oxocyclohexane-1-carboxylate Chemical compound CCOC(=O)C1CCC(Br)C(=O)C1 UDLLBXAEMDYVSW-UHFFFAOYSA-N 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- IFRZMLXGVMVTCG-UHFFFAOYSA-N n-[(2-ethyl-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl)methyl]ethanamine Chemical compound C1C(CNCC)CCC2=C1SC(CC)=N2 IFRZMLXGVMVTCG-UHFFFAOYSA-N 0.000 description 2
- RPJDREGXHFGIBJ-UHFFFAOYSA-N n-methyl-1-(2-methyl-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl)methanamine Chemical compound C1C(CNC)CCC2=C1SC(C)=N2 RPJDREGXHFGIBJ-UHFFFAOYSA-N 0.000 description 2
- POVNCAJVJMSJEW-UHFFFAOYSA-N n-methyl-1-(2-propan-2-yl-4,5,6,7-tetrahydro-1,3-benzothiazol-5-yl)methanamine Chemical compound C1C(CNC)CCC2=C1N=C(C(C)C)S2 POVNCAJVJMSJEW-UHFFFAOYSA-N 0.000 description 2
- QBOJNGZZIUUNRV-UHFFFAOYSA-N n-methyl-1-(4,5,6,7-tetrahydro-1,3-benzothiazol-5-yl)methanamine Chemical compound C1C(CNC)CCC2=C1N=CS2 QBOJNGZZIUUNRV-UHFFFAOYSA-N 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- TXQRWUYYHVIJDU-UHFFFAOYSA-N (2-butyl-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl)methanol Chemical compound OCC1CCCC2=C1N=C(CCCC)S2 TXQRWUYYHVIJDU-UHFFFAOYSA-N 0.000 description 1
- BPNGJVMDJUTXGZ-UHFFFAOYSA-N (2-butyl-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl)methyl 4-methylbenzenesulfonate Chemical compound C1CCC=2SC(CCCC)=NC=2C1COS(=O)(=O)C1=CC=C(C)C=C1 BPNGJVMDJUTXGZ-UHFFFAOYSA-N 0.000 description 1
- YAUOABDEZLLLRA-UHFFFAOYSA-N (2-butyl-4,5,6,7-tetrahydro-1,3-benzothiazol-5-yl)methanol Chemical compound C1C(CO)CCC2=C1N=C(CCCC)S2 YAUOABDEZLLLRA-UHFFFAOYSA-N 0.000 description 1
- SJFKMVBIYATFGJ-UHFFFAOYSA-N (2-butyl-4,5,6,7-tetrahydro-1,3-benzothiazol-5-yl)methyl 4-methylbenzenesulfonate Chemical compound C1CC=2SC(CCCC)=NC=2CC1COS(=O)(=O)C1=CC=C(C)C=C1 SJFKMVBIYATFGJ-UHFFFAOYSA-N 0.000 description 1
- GDSLLGUBDBYYID-UHFFFAOYSA-N (2-ethyl-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl)methanol Chemical compound C1CC(CO)CC2=C1N=C(CC)S2 GDSLLGUBDBYYID-UHFFFAOYSA-N 0.000 description 1
- PHTNBGSBZBPUOC-UHFFFAOYSA-N (2-methyl-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl)methanol Chemical compound OCC1CCCC2=C1N=C(C)S2 PHTNBGSBZBPUOC-UHFFFAOYSA-N 0.000 description 1
- ORLSLKMDNKEXQM-UHFFFAOYSA-N (2-methyl-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl)methyl 4-methylbenzenesulfonate Chemical compound C1CCC=2SC(C)=NC=2C1COS(=O)(=O)C1=CC=C(C)C=C1 ORLSLKMDNKEXQM-UHFFFAOYSA-N 0.000 description 1
- VQVKKIYLIHOYPJ-UHFFFAOYSA-N (2-methyl-4,5,6,7-tetrahydro-1,3-benzothiazol-5-yl)methanol Chemical compound C1C(CO)CCC2=C1N=C(C)S2 VQVKKIYLIHOYPJ-UHFFFAOYSA-N 0.000 description 1
- ZNYAYVDQWPROFY-UHFFFAOYSA-N (2-methyl-4,5,6,7-tetrahydro-1,3-benzothiazol-5-yl)methyl 4-methylbenzenesulfonate Chemical compound C1CC=2SC(C)=NC=2CC1COS(=O)(=O)C1=CC=C(C)C=C1 ZNYAYVDQWPROFY-UHFFFAOYSA-N 0.000 description 1
- QXXDTKKDDQWYBZ-UHFFFAOYSA-N (2-methyl-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl)methanol Chemical compound C1CC(CO)CC2=C1N=C(C)S2 QXXDTKKDDQWYBZ-UHFFFAOYSA-N 0.000 description 1
- QKSPJEDIMBBXEK-UHFFFAOYSA-N (2-propan-2-yl-4,5,6,7-tetrahydro-1,3-benzothiazol-5-yl)methanol Chemical compound C1C(CO)CCC2=C1N=C(C(C)C)S2 QKSPJEDIMBBXEK-UHFFFAOYSA-N 0.000 description 1
- CCWUIBHSYCEHNT-UHFFFAOYSA-N (2-propan-2-yl-4,5,6,7-tetrahydro-1,3-benzothiazol-5-yl)methyl 4-methylbenzenesulfonate Chemical compound C1CC=2SC(C(C)C)=NC=2CC1COS(=O)(=O)C1=CC=C(C)C=C1 CCWUIBHSYCEHNT-UHFFFAOYSA-N 0.000 description 1
- NPCLRBQYESMUPD-UHFFFAOYSA-N 2-methylpropanethioamide Chemical compound CC(C)C(N)=S NPCLRBQYESMUPD-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OPITVRBXKRIOFT-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1,3-benzothiazol-4-ylmethanol Chemical compound OCC1CCCC2=C1N=CS2 OPITVRBXKRIOFT-UHFFFAOYSA-N 0.000 description 1
- CAJANQXVJVNVKK-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1,3-benzothiazol-4-ylmethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1C(N=CS2)=C2CCC1 CAJANQXVJVNVKK-UHFFFAOYSA-N 0.000 description 1
- YEWRYMJJBNLVRG-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1,3-benzothiazol-5-ylmethanol Chemical compound C1C(CO)CCC2=C1N=CS2 YEWRYMJJBNLVRG-UHFFFAOYSA-N 0.000 description 1
- VTXJLZDBWYUHPI-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1,3-benzothiazol-5-ylmethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1CC(N=CS2)=C2CC1 VTXJLZDBWYUHPI-UHFFFAOYSA-N 0.000 description 1
- JZAVASOFSYHZIZ-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1,3-benzothiazol-6-ylmethanol Chemical compound C1C(CO)CCC2=C1SC=N2 JZAVASOFSYHZIZ-UHFFFAOYSA-N 0.000 description 1
- RRGACZQNUDSSSU-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1,3-benzothiazol-6-ylmethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1CC(SC=N2)=C2CC1 RRGACZQNUDSSSU-UHFFFAOYSA-N 0.000 description 1
- MNPZWXLNHBUNIG-UHFFFAOYSA-N 5-acetyl-2-bromocyclohexan-1-one Chemical compound CC(=O)C1CCC(Br)C(=O)C1 MNPZWXLNHBUNIG-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 206010065929 Cardiovascular insufficiency Diseases 0.000 description 1
- 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 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000008321 arterial blood flow Effects 0.000 description 1
- 210000004191 axillary artery Anatomy 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- UROXPWFRQZOHOO-UHFFFAOYSA-N ethyl 2-butyl-4,5,6,7-tetrahydro-1,3-benzothiazole-4-carboxylate Chemical compound CCOC(=O)C1CCCC2=C1N=C(CCCC)S2 UROXPWFRQZOHOO-UHFFFAOYSA-N 0.000 description 1
- XCYGVEIYRCAGGJ-UHFFFAOYSA-N ethyl 2-butyl-4,5,6,7-tetrahydro-1,3-benzothiazole-5-carboxylate Chemical compound C1C(C(=O)OCC)CCC2=C1N=C(CCCC)S2 XCYGVEIYRCAGGJ-UHFFFAOYSA-N 0.000 description 1
- TVULSXCAFGMKQR-UHFFFAOYSA-N ethyl 2-methyl-4,5,6,7-tetrahydro-1,3-benzothiazole-4-carboxylate Chemical compound CCOC(=O)C1CCCC2=C1N=C(C)S2 TVULSXCAFGMKQR-UHFFFAOYSA-N 0.000 description 1
- KLYDWMHKPCZUCD-UHFFFAOYSA-N ethyl 2-methyl-4,5,6,7-tetrahydro-1,3-benzothiazole-5-carboxylate Chemical compound C1C(C(=O)OCC)CCC2=C1N=C(C)S2 KLYDWMHKPCZUCD-UHFFFAOYSA-N 0.000 description 1
- FCNBWQFEVMWBAH-UHFFFAOYSA-N ethyl 2-methyl-4,5,6,7-tetrahydro-1,3-benzothiazole-6-carboxylate Chemical compound C1C(C(=O)OCC)CCC2=C1SC(C)=N2 FCNBWQFEVMWBAH-UHFFFAOYSA-N 0.000 description 1
- NOJBYOKLFOGIKG-UHFFFAOYSA-N ethyl 2-propan-2-yl-4,5,6,7-tetrahydro-1,3-benzothiazole-5-carboxylate Chemical compound C1C(C(=O)OCC)CCC2=C1N=C(C(C)C)S2 NOJBYOKLFOGIKG-UHFFFAOYSA-N 0.000 description 1
- CZWCQRFMTZHZLB-UHFFFAOYSA-N ethyl 4,5,6,7-tetrahydro-1,3-benzothiazole-4-carboxylate Chemical compound CCOC(=O)C1CCCC2=C1N=CS2 CZWCQRFMTZHZLB-UHFFFAOYSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000003447 ipsilateral effect Effects 0.000 description 1
- 108010063993 lens intrinsic protein MP 64 Proteins 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- XRIUNXOTAHFTCP-UHFFFAOYSA-N methyl 4,5,6,7-tetrahydro-1,3-benzothiazole-5-carboxylate Chemical compound C1C(C(=O)OC)CCC2=C1N=CS2 XRIUNXOTAHFTCP-UHFFFAOYSA-N 0.000 description 1
- NPNURABQPHGRPL-UHFFFAOYSA-N n-(4,5,6,7-tetrahydro-1,3-benzothiazol-6-ylmethyl)propan-1-amine Chemical compound C1C(CNCCC)CCC2=C1SC=N2 NPNURABQPHGRPL-UHFFFAOYSA-N 0.000 description 1
- YMPQTOGHEILJPC-UHFFFAOYSA-N n-methyl-1-(2-methyl-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl)methanamine Chemical compound CNCC1CCCC2=C1N=C(C)S2 YMPQTOGHEILJPC-UHFFFAOYSA-N 0.000 description 1
- YNODPVUCUARLIY-UHFFFAOYSA-N n-methyl-1-(4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl)methanamine Chemical compound CNCC1CCCC2=C1N=CS2 YNODPVUCUARLIY-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- WPZSAUFQHYFIPG-UHFFFAOYSA-N propanethioamide Chemical compound CCC(N)=S WPZSAUFQHYFIPG-UHFFFAOYSA-N 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Heart & Thoracic Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7915774A FR2459239A1 (fr) | 1979-06-20 | 1979-06-20 | Nouveaux derives amines du benzothiazole, leur procede de preparation et leur application en therapeutique |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS567772A JPS567772A (en) | 1981-01-27 |
| JPS6342622B2 true JPS6342622B2 (show.php) | 1988-08-24 |
Family
ID=9226843
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8384480A Granted JPS567772A (en) | 1979-06-20 | 1980-06-20 | Novel amino derivative of benzothiazole and its manufacture |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US4337343A (show.php) |
| EP (1) | EP0021940B1 (show.php) |
| JP (1) | JPS567772A (show.php) |
| CA (1) | CA1140136A (show.php) |
| DE (1) | DE3061672D1 (show.php) |
| ES (1) | ES492578A0 (show.php) |
| FR (1) | FR2459239A1 (show.php) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3572485D1 (en) * | 1984-12-22 | 1989-09-28 | Thomae Gmbh Dr K | Tetrahydro-benzothiazoles, their production and their use as intermediates or drugs |
| JPS62292229A (ja) * | 1986-06-13 | 1987-12-18 | Toyo Seikan Kaisha Ltd | 易開口性蓋の製造方法 |
| DE3620813A1 (de) | 1986-06-21 | 1987-12-23 | Boehringer Ingelheim Kg | Neue tetrahydro-benzothiazole, ihre herstellung und verwendung |
| WO2008001200A2 (en) * | 2006-06-29 | 2008-01-03 | Antares Pharma Ipl Ag | Transdermal composition having enhanced color stability |
| CN104193761B (zh) | 2009-12-04 | 2017-10-17 | 桑诺维恩药品公司 | 多环化合物及其使用方法 |
| BR112019001407A2 (pt) | 2016-07-29 | 2019-07-09 | Sunovion Pharmaceuticals Inc. | compostos e composições e usos dos mesmos |
| SG10202100724UA (en) | 2016-07-29 | 2021-03-30 | Sunovion Pharmaceuticals Inc | Compounds and compositions and uses thereof |
| EP3582815A1 (en) | 2017-02-16 | 2019-12-25 | Sunovion Pharmaceuticals Inc. | Methods of treating schizophrenia |
| MX2020000523A (es) | 2017-08-02 | 2020-08-20 | Sunovion Pharmaceuticals Inc | Compuestos de isocromano y usos de los mismos. |
| SG11202007823PA (en) | 2018-02-16 | 2020-09-29 | Sunovion Pharmaceuticals Inc | Salts, crystal forms, and production methods thereof |
| JP7703449B2 (ja) | 2019-03-14 | 2025-07-07 | スミトモ・ファーマ・アメリカ・インコーポレイテッド | イソクロマニル化合物の塩およびその結晶体、ならびにそれらの製造方法、治療用途および医薬組成物 |
| KR20230003503A (ko) | 2020-04-14 | 2023-01-06 | 선오비온 파마슈티컬스 인코포레이티드 | 신경학적 및 정신의학적 장애의 치료를 위한 (S)-(4,5-디히드로-7H-티에노[2,3-c]피란-7-일)-N-메틸메탄아민 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE792402A (fr) * | 1971-12-07 | 1973-06-07 | Ciba Geigy | Composes heterocycliques azotes et medicaments anthelminthiqueset antimicrobiens qui en contiennent |
| JPS4930360A (show.php) * | 1972-03-04 | 1974-03-18 | ||
| JPS50108261A (show.php) * | 1974-02-12 | 1975-08-26 | ||
| FR2406635A1 (fr) * | 1977-10-24 | 1979-05-18 | Logeais Labor Jacques | Nouveaux derives du benzo(d)thiazole, leur procede de preparation et leurs applications en therapeutique |
-
1979
- 1979-06-20 FR FR7915774A patent/FR2459239A1/fr active Granted
-
1980
- 1980-06-10 DE DE8080400831T patent/DE3061672D1/de not_active Expired
- 1980-06-10 EP EP80400831A patent/EP0021940B1/fr not_active Expired
- 1980-06-12 CA CA000353873A patent/CA1140136A/en not_active Expired
- 1980-06-18 US US06/160,458 patent/US4337343A/en not_active Expired - Lifetime
- 1980-06-19 ES ES492578A patent/ES492578A0/es active Granted
- 1980-06-20 JP JP8384480A patent/JPS567772A/ja active Granted
-
1982
- 1982-03-10 US US06/356,617 patent/US4423056A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP0021940B1 (fr) | 1983-01-19 |
| JPS567772A (en) | 1981-01-27 |
| EP0021940A1 (fr) | 1981-01-07 |
| ES8103071A1 (es) | 1981-02-16 |
| FR2459239B1 (show.php) | 1982-09-10 |
| FR2459239A1 (fr) | 1981-01-09 |
| CA1140136A (en) | 1983-01-25 |
| DE3061672D1 (en) | 1983-02-24 |
| ES492578A0 (es) | 1981-02-16 |
| US4423056A (en) | 1983-12-27 |
| US4337343A (en) | 1982-06-29 |
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