NO132094B - - Google Patents
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- Publication number
- NO132094B NO132094B NO2575/70A NO257570A NO132094B NO 132094 B NO132094 B NO 132094B NO 2575/70 A NO2575/70 A NO 2575/70A NO 257570 A NO257570 A NO 257570A NO 132094 B NO132094 B NO 132094B
- Authority
- NO
- Norway
- Prior art keywords
- tetrahydroisoquinoline
- sulfonyl
- propionyl
- cyclohexyl
- sulfonamide
- Prior art date
Links
- -1 α-naphthyl- Chemical group 0.000 claims description 57
- 150000001875 compounds Chemical class 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 229940100389 Sulfonylurea Drugs 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 239000007858 starting material Substances 0.000 claims description 7
- 239000003513 alkali Substances 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 6
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims description 5
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- FOOQESAZHHBZBD-UHFFFAOYSA-N 1-cyclohexyl-3-[[2-(2-phenylpropanoyl)-3,4-dihydro-1H-isoquinolin-7-yl]sulfonyl]urea Chemical compound C1(=CC=CC=C1)C(C(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)NC(=O)NC1CCCCC1)C FOOQESAZHHBZBD-UHFFFAOYSA-N 0.000 claims description 2
- ZPZBJMYPHWKXSS-UHFFFAOYSA-N CC1=CC=C(C=C1)C(C(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)NC(=O)NC1CCCCC1)C Chemical compound CC1=CC=C(C=C1)C(C(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)NC(=O)NC1CCCCC1)C ZPZBJMYPHWKXSS-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000006267 biphenyl group Chemical group 0.000 claims description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate group Chemical group [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical compound O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 5
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- RCIVSMPVTWFBIS-UHFFFAOYSA-N ClC1=CC=C(C=C1)C(C(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)NC(=O)NC1CCCCC1)C Chemical compound ClC1=CC=C(C=C1)C(C(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)NC(=O)NC1CCCCC1)C RCIVSMPVTWFBIS-UHFFFAOYSA-N 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 79
- 159000000000 sodium salts Chemical class 0.000 description 78
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 50
- KQWGXHWJMSMDJJ-UHFFFAOYSA-N cyclohexyl isocyanate Chemical compound O=C=NC1CCCCC1 KQWGXHWJMSMDJJ-UHFFFAOYSA-N 0.000 description 44
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 42
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 38
- 239000000243 solution Substances 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical class O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
- 238000001704 evaporation Methods 0.000 description 19
- 230000008020 evaporation Effects 0.000 description 19
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 229940124530 sulfonamide Drugs 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 150000003456 sulfonamides Chemical class 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
- 229960000583 acetic acid Drugs 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 10
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- 235000011121 sodium hydroxide Nutrition 0.000 description 8
- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 8
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
- 239000004202 carbamide Substances 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical compound OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000052 vinegar Substances 0.000 description 6
- 235000021419 vinegar Nutrition 0.000 description 6
- HFODCIWEQMGWCT-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline-7-sulfonamide;hydrochloride Chemical compound Cl.C1CNCC2=CC(S(=O)(=O)N)=CC=C21 HFODCIWEQMGWCT-UHFFFAOYSA-N 0.000 description 5
- IRUXSKJXJFMZPQ-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-3-benzazepine-7-sulfonamide Chemical compound C1CNCCC2=CC(S(=O)(=O)N)=CC=C21 IRUXSKJXJFMZPQ-UHFFFAOYSA-N 0.000 description 5
- WSBZVFWAVDZIJU-UHFFFAOYSA-N C1(=CC=CC=C1)CCC(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N Chemical compound C1(=CC=CC=C1)CCC(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N WSBZVFWAVDZIJU-UHFFFAOYSA-N 0.000 description 5
- 239000012670 alkaline solution Substances 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- UGLLZXSYRBMNOS-UHFFFAOYSA-N 1,2,3,4-tetrahydro-isoquinoline-7-sulfonic acid amide Chemical compound C1CNCC2=CC(S(=O)(=O)N)=CC=C21 UGLLZXSYRBMNOS-UHFFFAOYSA-N 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- ALJDYAQEODFQCX-UHFFFAOYSA-N ethyl N-[[2-(3-phenylpropanoyl)-3,4-dihydro-1H-isoquinolin-7-yl]sulfonyl]carbamate Chemical compound CCOC(=O)NS(=O)(=O)C1=CC2=C(CCN(C2)C(=O)CCC2=CC=CC=C2)C=C1 ALJDYAQEODFQCX-UHFFFAOYSA-N 0.000 description 4
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- AAFGZKYAEMJTLZ-UHFFFAOYSA-N 2-(2-phenylpropanoyl)-3,4-dihydro-1H-isoquinoline-7-sulfonamide Chemical compound C1(=CC=CC=C1)C(C(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N)C AAFGZKYAEMJTLZ-UHFFFAOYSA-N 0.000 description 3
- ILJBSAAGDQNOHZ-UHFFFAOYSA-N 2-[2-(4-chlorophenyl)propanoyl]-3,4-dihydro-1H-isoquinoline-7-sulfonamide Chemical compound ClC1=CC=C(C=C1)C(C(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N)C ILJBSAAGDQNOHZ-UHFFFAOYSA-N 0.000 description 3
- KSMVBYPXNKCPAJ-UHFFFAOYSA-N 4-Methylcyclohexylamine Chemical compound CC1CCC(N)CC1 KSMVBYPXNKCPAJ-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000002026 chloroform extract Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- AOCYHPQXGJBAQQ-UHFFFAOYSA-N ethyl n-sulfonylcarbamate Chemical compound CCOC(=O)N=S(=O)=O AOCYHPQXGJBAQQ-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000012948 isocyanate Substances 0.000 description 3
- 150000002513 isocyanates Chemical class 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- NABUFFLEHQEQPH-UHFFFAOYSA-N 1-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)ethanone Chemical compound C1CN(C(=O)C)CCC2=CC=CC=C21 NABUFFLEHQEQPH-UHFFFAOYSA-N 0.000 description 2
- JBPPSLURCSFQDH-UHFFFAOYSA-N 1-(3,4-dihydro-1h-isoquinolin-2-yl)ethanone Chemical compound C1=CC=C2CN(C(=O)C)CCC2=C1 JBPPSLURCSFQDH-UHFFFAOYSA-N 0.000 description 2
- XWVFMJLNNGXNSG-UHFFFAOYSA-N 1-(7-amino-3,4-dihydro-1h-isoquinolin-2-yl)ethanone Chemical compound C1=C(N)C=C2CN(C(=O)C)CCC2=C1 XWVFMJLNNGXNSG-UHFFFAOYSA-N 0.000 description 2
- BIGSDRLRUNXANK-UHFFFAOYSA-N 2-(3-phenylbutanoyl)-3,4-dihydro-1H-isoquinoline-7-sulfonamide Chemical compound C1(=CC=CC=C1)C(CC(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N)C BIGSDRLRUNXANK-UHFFFAOYSA-N 0.000 description 2
- XYVQFXSDLNCVQQ-UHFFFAOYSA-N 2-acetyl-3,4-dihydro-1h-isoquinoline-7-sulfonamide Chemical compound C1=C(S(N)(=O)=O)C=C2CN(C(=O)C)CCC2=C1 XYVQFXSDLNCVQQ-UHFFFAOYSA-N 0.000 description 2
- WZYNHWTZPLQOAG-UHFFFAOYSA-N C1(=CC=CC=C1)C(C(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)NC(OCC)=O)C Chemical compound C1(=CC=CC=C1)C(C(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)NC(OCC)=O)C WZYNHWTZPLQOAG-UHFFFAOYSA-N 0.000 description 2
- DBESOTBONSCZLF-UHFFFAOYSA-N C1(=CC=CC=C1)C(CC(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)NC(OCC)=O)C Chemical compound C1(=CC=CC=C1)C(CC(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)NC(OCC)=O)C DBESOTBONSCZLF-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 238000000297 Sandmeyer reaction Methods 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 150000007530 organic bases Chemical group 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- WZHRJGWXUCLILI-UHFFFAOYSA-N sulfonylcarbamic acid Chemical class OC(=O)N=S(=O)=O WZHRJGWXUCLILI-UHFFFAOYSA-N 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- VMEDBFRQSKKEEQ-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinolin-7-amine Chemical class C1CNCC2=CC(N)=CC=C21 VMEDBFRQSKKEEQ-UHFFFAOYSA-N 0.000 description 1
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical class C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 1
- FSYWMPRUEBTSIZ-UHFFFAOYSA-N 1-cyclohexyl-3-[[2-(4-methylbenzoyl)-3,4-dihydro-1H-isoquinolin-7-yl]sulfonyl]urea Chemical compound CC1=CC=C(C(=O)N2CC3=CC(=CC=C3CC2)S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 FSYWMPRUEBTSIZ-UHFFFAOYSA-N 0.000 description 1
- LOXPKSAIAHLVML-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-3-benzazepin-7-amine Chemical class C1CNCCC2=CC(N)=CC=C21 LOXPKSAIAHLVML-UHFFFAOYSA-N 0.000 description 1
- MWVMYAWMFTVYED-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-3-benzazepine Chemical class C1CNCCC2=CC=CC=C21 MWVMYAWMFTVYED-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- GSJVKPFXFCEEPQ-UHFFFAOYSA-N 2-(3-phenylpentanoyl)-3,4-dihydro-1H-isoquinoline-7-sulfonamide Chemical compound C1(=CC=CC=C1)C(CC(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N)CC GSJVKPFXFCEEPQ-UHFFFAOYSA-N 0.000 description 1
- PFDBEACWLCHWRZ-UHFFFAOYSA-N 2-(4-bromophenyl)propanoic acid Chemical compound OC(=O)C(C)C1=CC=C(Br)C=C1 PFDBEACWLCHWRZ-UHFFFAOYSA-N 0.000 description 1
- YOZILQVNIWNPFP-UHFFFAOYSA-N 2-(4-chlorophenyl)propanoic acid Chemical compound OC(=O)C(C)C1=CC=C(Cl)C=C1 YOZILQVNIWNPFP-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- APSGVUXOAHSBGR-UHFFFAOYSA-N 2-[2-(3,4-dichlorophenyl)propanoyl]-3,4-dihydro-1H-isoquinoline-7-sulfonamide Chemical compound ClC=1C=C(C=CC1Cl)C(C(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N)C APSGVUXOAHSBGR-UHFFFAOYSA-N 0.000 description 1
- UXSMEOLJRBKPKI-UHFFFAOYSA-N 2-[3-(3-chlorophenyl)propanoyl]-3,4-dihydro-1H-isoquinoline-7-sulfonamide Chemical compound ClC=1C=C(C=CC1)CCC(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N UXSMEOLJRBKPKI-UHFFFAOYSA-N 0.000 description 1
- MAUSSGMKFIPNAQ-UHFFFAOYSA-N 3-acetyl-1,2,4,5-tetrahydro-3-benzazepine-7-sulfonamide Chemical compound C(C)(=O)N1CCC2=C(CC1)C=CC(=C2)S(=O)(=O)N MAUSSGMKFIPNAQ-UHFFFAOYSA-N 0.000 description 1
- MFEILWXBDBCWKF-UHFFFAOYSA-N 3-phenylpropanoyl chloride Chemical compound ClC(=O)CCC1=CC=CC=C1 MFEILWXBDBCWKF-UHFFFAOYSA-N 0.000 description 1
- IKQCKANHUYSABG-UHFFFAOYSA-N 4-ethylcyclohexan-1-amine Chemical compound CCC1CCC(N)CC1 IKQCKANHUYSABG-UHFFFAOYSA-N 0.000 description 1
- 102100031126 6-phosphogluconolactonase Human genes 0.000 description 1
- 108010029731 6-phosphogluconolactonase Proteins 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 238000006418 Brown reaction Methods 0.000 description 1
- GUCLPCNETRTMIK-UHFFFAOYSA-N C(C)OC1=CC=C(C=C1)C(C(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N)C Chemical compound C(C)OC1=CC=C(C=C1)C(C(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N)C GUCLPCNETRTMIK-UHFFFAOYSA-N 0.000 description 1
- ATAAGXSCUHYATC-UHFFFAOYSA-N C(C1=CC=CC=C1)(=O)CC(=O)C1NCCC2=CC=C(C=C12)S(=O)(=O)N Chemical compound C(C1=CC=CC=C1)(=O)CC(=O)C1NCCC2=CC=C(C=C12)S(=O)(=O)N ATAAGXSCUHYATC-UHFFFAOYSA-N 0.000 description 1
- NASKLOJEFRXNCN-UHFFFAOYSA-N C(CC(C)C)(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N Chemical compound C(CC(C)C)(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N NASKLOJEFRXNCN-UHFFFAOYSA-N 0.000 description 1
- RSPVHMRCRNKTOA-UHFFFAOYSA-N C(CCC)(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N Chemical compound C(CCC)(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N RSPVHMRCRNKTOA-UHFFFAOYSA-N 0.000 description 1
- UIWGHTMEJUQOTF-UHFFFAOYSA-N C1(=CC=C(C=C1)CCC(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N)C Chemical compound C1(=CC=C(C=C1)CCC(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N)C UIWGHTMEJUQOTF-UHFFFAOYSA-N 0.000 description 1
- FSWUULHCNDYMGQ-UHFFFAOYSA-N CC(C(CC(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N)C1=CC=CC=C1)C Chemical compound CC(C(CC(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N)C1=CC=CC=C1)C FSWUULHCNDYMGQ-UHFFFAOYSA-N 0.000 description 1
- GRALOFCMPMMESQ-UHFFFAOYSA-N COC1=C(C=CC=C1)CCC(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N Chemical compound COC1=C(C=CC=C1)CCC(=O)N1CC2=CC(=CC=C2CC1)S(=O)(=O)N GRALOFCMPMMESQ-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical group CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 1
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 1
- 108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 1
- 102000005548 Hexokinase Human genes 0.000 description 1
- 108700040460 Hexokinases Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- ACFIXJIJDZMPPO-NNYOXOHSSA-J NADPH(4-) Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP([O-])(=O)OP([O-])(=O)OC[C@@H]2[C@H]([C@@H](OP([O-])([O-])=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-J 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical group 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000004531 blood pressure lowering effect Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- VXVVUHQULXCUPF-UHFFFAOYSA-N cycloheptanamine Chemical compound NC1CCCCCC1 VXVVUHQULXCUPF-UHFFFAOYSA-N 0.000 description 1
- WUESWDIHTKHGQA-UHFFFAOYSA-N cyclohexylurea Chemical compound NC(=O)NC1CCCCC1 WUESWDIHTKHGQA-UHFFFAOYSA-N 0.000 description 1
- HSOHBWMXECKEKV-UHFFFAOYSA-N cyclooctanamine Chemical compound NC1CCCCCCC1 HSOHBWMXECKEKV-UHFFFAOYSA-N 0.000 description 1
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- TXQDTCFYVNDVJK-UHFFFAOYSA-N ethyl N-ethoxycarbonyl-N-[[2-(3-phenylpropanoyl)-3,4-dihydro-1H-isoquinolin-7-yl]sulfonyl]carbamate Chemical compound C(=O)(OCC)N(S(=O)(=O)C1=CC=C2CCN(CC2=C1)C(CCC1=CC=CC=C1)=O)C(=O)OCC TXQDTCFYVNDVJK-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical compound OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- HNHVTXYLRVGMHD-UHFFFAOYSA-N n-butyl isocyanate Chemical compound CCCCN=C=O HNHVTXYLRVGMHD-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000004540 pour-on Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/06—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19691933388 DE1933388A1 (de) | 1969-07-01 | 1969-07-01 | Neue Sulfonylharnstoffe und Verfahren zu ihrer Herstellung |
| DE19702027436 DE2027436A1 (en) | 1970-06-04 | 1970-06-04 | Sulphenylurea cpds, hypoglycaemics |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO132094B true NO132094B (enrdf_load_stackoverflow) | 1975-06-09 |
| NO132094C NO132094C (enrdf_load_stackoverflow) | 1975-09-17 |
Family
ID=25757577
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO2575/70A NO132094C (enrdf_load_stackoverflow) | 1969-07-01 | 1970-06-30 |
Country Status (16)
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7229986B2 (en) | 2000-05-16 | 2007-06-12 | Takeda Pharmaceutical Company Ltd. | Melanin-concentrating hormone antagonist |
-
1970
- 1970-06-17 FI FI701712A patent/FI49828C/fi active
- 1970-06-24 SE SE08771/70A patent/SE357745B/xx unknown
- 1970-06-25 RO RO63739A patent/RO56857A/ro unknown
- 1970-06-26 BG BG16831A patent/BG18181A1/xx unknown
- 1970-06-27 ES ES381248A patent/ES381248A1/es not_active Expired
- 1970-06-29 CH CH982470A patent/CH536842A/de not_active IP Right Cessation
- 1970-06-30 NO NO2575/70A patent/NO132094C/no unknown
- 1970-06-30 PL PL1970141708A patent/PL81112B1/pl unknown
- 1970-06-30 AT AT586870A patent/AT301568B/de not_active IP Right Cessation
- 1970-06-30 GB GB3172270A patent/GB1313539A/en not_active Expired
- 1970-06-30 IE IE856/70A patent/IE34359B1/xx unknown
- 1970-06-30 IL IL34820A patent/IL34820A/en unknown
- 1970-06-30 DK DK338970AA patent/DK127928B/da unknown
- 1970-06-30 BE BE752760D patent/BE752760A/xx unknown
- 1970-07-01 NL NL7009704A patent/NL7009704A/xx unknown
- 1970-07-01 FR FR7024368A patent/FR2059465B1/fr not_active Expired
-
1971
- 1971-07-19 ES ES393416A patent/ES393416A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| NL7009704A (enrdf_load_stackoverflow) | 1971-01-05 |
| IE34359B1 (en) | 1975-04-16 |
| FR2059465A1 (enrdf_load_stackoverflow) | 1971-06-04 |
| SE357745B (enrdf_load_stackoverflow) | 1973-07-09 |
| IL34820A (en) | 1973-08-29 |
| DK127928B (da) | 1974-02-04 |
| RO56857A (enrdf_load_stackoverflow) | 1974-12-15 |
| NO132094C (enrdf_load_stackoverflow) | 1975-09-17 |
| ES393416A1 (es) | 1974-06-01 |
| FR2059465B1 (enrdf_load_stackoverflow) | 1974-03-22 |
| IE34359L (en) | 1971-01-01 |
| BG18181A1 (enrdf_load_stackoverflow) | 1974-09-02 |
| CH536842A (de) | 1973-05-15 |
| IL34820A0 (en) | 1970-09-17 |
| PL81112B1 (en) | 1975-08-30 |
| FI49828C (fi) | 1975-10-10 |
| FI49828B (enrdf_load_stackoverflow) | 1975-06-30 |
| ES381248A1 (es) | 1972-11-01 |
| BE752760A (fr) | 1970-12-30 |
| GB1313539A (en) | 1973-04-11 |
| AT301568B (de) | 1972-09-11 |
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