CS264288B2 - Process for preparing new dihydrobenzofuran- and chromat-carboxamides - Google Patents
Process for preparing new dihydrobenzofuran- and chromat-carboxamides Download PDFInfo
- Publication number
- CS264288B2 CS264288B2 CS87578A CS57887A CS264288B2 CS 264288 B2 CS264288 B2 CS 264288B2 CS 87578 A CS87578 A CS 87578A CS 57887 A CS57887 A CS 57887A CS 264288 B2 CS264288 B2 CS 264288B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- water
- filtered
- methyl
- solution
- dried
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 27
- 239000002253 acid Substances 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- -1 cyclopropylmethylsulphonyl group Chemical group 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 230000003287 optical effect Effects 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 2
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 150
- 239000000243 solution Substances 0.000 description 136
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 135
- 239000000047 product Substances 0.000 description 109
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 92
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 83
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 78
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 77
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 69
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 62
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 description 62
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 60
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 54
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 53
- 239000000203 mixture Substances 0.000 description 46
- 239000013078 crystal Substances 0.000 description 42
- 239000000706 filtrate Substances 0.000 description 38
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 38
- 238000001816 cooling Methods 0.000 description 37
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 239000002244 precipitate Substances 0.000 description 33
- 229910021529 ammonia Inorganic materials 0.000 description 31
- 239000011541 reaction mixture Substances 0.000 description 31
- 238000005406 washing Methods 0.000 description 31
- 238000002844 melting Methods 0.000 description 28
- 230000008018 melting Effects 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- 238000004821 distillation Methods 0.000 description 24
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 21
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 19
- 238000010438 heat treatment Methods 0.000 description 19
- 229910000027 potassium carbonate Inorganic materials 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 239000003610 charcoal Substances 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
- 238000003756 stirring Methods 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 15
- 229960004046 apomorphine Drugs 0.000 description 15
- 238000009835 boiling Methods 0.000 description 15
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 15
- 238000010908 decantation Methods 0.000 description 13
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 12
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 239000007789 gas Substances 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- 230000003042 antagnostic effect Effects 0.000 description 7
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- QFIYFROFRTUSPW-UHFFFAOYSA-N [1-(cyclopropylmethyl)pyrrolidin-2-yl]methanamine Chemical compound NCC1CCCN1CC1CC1 QFIYFROFRTUSPW-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000001530 fumaric acid Substances 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 208000009132 Catalepsy Diseases 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 206010047853 Waxy flexibility Diseases 0.000 description 5
- PUVRPONDSAVLJE-UHFFFAOYSA-N [1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methanamine Chemical compound NCC1CCCN1CC1=CCCCC1 PUVRPONDSAVLJE-UHFFFAOYSA-N 0.000 description 5
- 229940025084 amphetamine Drugs 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 230000033001 locomotion Effects 0.000 description 5
- CEQFOVLGLXCDCX-WUKNDPDISA-N methyl red Chemical compound C1=CC(N(C)C)=CC=C1\N=N\C1=CC=CC=C1C(O)=O CEQFOVLGLXCDCX-WUKNDPDISA-N 0.000 description 5
- 230000007659 motor function Effects 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 239000011343 solid material Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- UNRBEYYLYRXYCG-UHFFFAOYSA-N (1-ethylpyrrolidin-2-yl)methanamine Chemical compound CCN1CCCC1CN UNRBEYYLYRXYCG-UHFFFAOYSA-N 0.000 description 4
- 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 4
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 4
- AZPNKTZFUWEHDT-UHFFFAOYSA-N 6-(cyclopropylmethylsulfonyl)-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound C=1C=2CCCOC=2C(C(=O)O)=CC=1S(=O)(=O)CC1CC1 AZPNKTZFUWEHDT-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 230000002269 spontaneous effect Effects 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- ZHKWLZDQDAJMDE-UHFFFAOYSA-N 4-amino-5-chloro-2-methyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound OC(=O)C1=CC(Cl)=C(N)C2=C1OC(C)C2 ZHKWLZDQDAJMDE-UHFFFAOYSA-N 0.000 description 3
- WCLWARCNRCZCLX-UHFFFAOYSA-N 5-(cyclopropylmethylsulfonyl)-2-methyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound C=1C(C(O)=O)=C2OC(C)CC2=CC=1S(=O)(=O)CC1CC1 WCLWARCNRCZCLX-UHFFFAOYSA-N 0.000 description 3
- VTWDFRYGJWVOCB-UHFFFAOYSA-N 5-bromo-6-chlorosulfonyl-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound C1CCOC2=C1C(Br)=C(S(Cl)(=O)=O)C=C2C(=O)O VTWDFRYGJWVOCB-UHFFFAOYSA-N 0.000 description 3
- IKLTWEQRKUTUMF-UHFFFAOYSA-N 5-chloro-n-[[1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methyl]-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound C=1C(Cl)=CC=2CCOC=2C=1C(=O)NCC1CCCN1CC1=CCCCC1 IKLTWEQRKUTUMF-UHFFFAOYSA-N 0.000 description 3
- JKNYUUWDTUMXKG-UHFFFAOYSA-N 5-chlorosulfonyl-2-methyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound ClS(=O)(=O)C1=CC(C(O)=O)=C2OC(C)CC2=C1 JKNYUUWDTUMXKG-UHFFFAOYSA-N 0.000 description 3
- WFQGBZVMZKKVIY-UHFFFAOYSA-N 6-chlorosulfonyl-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound C1CCOC2=C1C=C(S(Cl)(=O)=O)C=C2C(=O)O WFQGBZVMZKKVIY-UHFFFAOYSA-N 0.000 description 3
- SXWUHKNCRQSTBA-UHFFFAOYSA-N 6-ethylsulfonyl-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound C1CCOC2=C1C=C(S(=O)(=O)CC)C=C2C(O)=O SXWUHKNCRQSTBA-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 3
- 230000001476 alcoholic effect Effects 0.000 description 3
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 3
- VJGNLOIQCWLBJR-UHFFFAOYSA-M benzyl(tributyl)azanium;chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CC1=CC=CC=C1 VJGNLOIQCWLBJR-UHFFFAOYSA-M 0.000 description 3
- 239000001569 carbon dioxide Substances 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 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
- 230000009194 climbing Effects 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 235000010265 sodium sulphite Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- DWCDRFVMIPLSMY-WLHGVMLRSA-N (e)-but-2-enedioic acid;6-chloro-n-[[1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methyl]-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound OC(=O)\C=C\C(O)=O.C=1C(Cl)=CC=2CCCOC=2C=1C(=O)NCC1CCCN1CC1=CCCCC1 DWCDRFVMIPLSMY-WLHGVMLRSA-N 0.000 description 2
- IAIORIGGWXAHOG-WLHGVMLRSA-N (e)-but-2-enedioic acid;n-[(1-ethylpyrrolidin-2-yl)methyl]-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound OC(=O)\C=C\C(O)=O.CCN1CCCC1CNC(=O)C1=CC=CC2=C1OCCC2 IAIORIGGWXAHOG-WLHGVMLRSA-N 0.000 description 2
- GGSGUFURNLIODZ-UHFFFAOYSA-N 2-methyl-5-(methylsulfamoyl)-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound OC(=O)C1=CC(S(=O)(=O)NC)=CC2=C1OC(C)C2 GGSGUFURNLIODZ-UHFFFAOYSA-N 0.000 description 2
- JVYRMZXDRCKMNK-UHFFFAOYSA-N 2-methyl-5-sulfanyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound SC1=CC(C(O)=O)=C2OC(C)CC2=C1 JVYRMZXDRCKMNK-UHFFFAOYSA-N 0.000 description 2
- LOFOWPRKKPHPDW-UHFFFAOYSA-N 3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound C1CCOC2=C1C=CC=C2C(=O)O LOFOWPRKKPHPDW-UHFFFAOYSA-N 0.000 description 2
- QVCKVMSEINXIDN-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-n,2-dimethyl-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound CCN(CC)CCN(C)C(=O)C1=CC(Cl)=C(N)C2=C1OC(C)C2 QVCKVMSEINXIDN-UHFFFAOYSA-N 0.000 description 2
- QUJARWZEVGNLIL-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-n,2-dimethyl-2,3-dihydro-1-benzofuran-7-carboxamide;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.CCN(CC)CCN(C)C(=O)C1=CC(Cl)=C(N)C2=C1OC(C)C2 QUJARWZEVGNLIL-UHFFFAOYSA-N 0.000 description 2
- PDDSSGRKQCLERH-UHFFFAOYSA-N 5-amino-6-(methylsulfamoyl)-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound O1CCCC2=C(N)C(S(=O)(=O)NC)=CC(C(O)=O)=C21 PDDSSGRKQCLERH-UHFFFAOYSA-N 0.000 description 2
- HMAQONNHUBCKQM-UHFFFAOYSA-N 5-amino-n-[[1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-6-ethylsulfonyl-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C=12OCCCC2=C(N)C(S(=O)(=O)CC)=CC=1C(=O)NCC1CCCN1CC1CC1 HMAQONNHUBCKQM-UHFFFAOYSA-N 0.000 description 2
- ZZVRSHCOXWQTMD-UHFFFAOYSA-N 5-bromo-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound C1CCOC2=C1C(Br)=CC=C2C(=O)O ZZVRSHCOXWQTMD-UHFFFAOYSA-N 0.000 description 2
- DMMOXNRMYOHPOG-UHFFFAOYSA-N 5-bromo-6-(methylsulfamoyl)-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound O1CCCC2=C(Br)C(S(=O)(=O)NC)=CC(C(O)=O)=C21 DMMOXNRMYOHPOG-UHFFFAOYSA-N 0.000 description 2
- BBQBSUIZHLFZFL-UHFFFAOYSA-N 5-bromo-6-ethylsulfonyl-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound O1CCCC2=C(Br)C(S(=O)(=O)CC)=CC(C(O)=O)=C21 BBQBSUIZHLFZFL-UHFFFAOYSA-N 0.000 description 2
- SGPAPRPKRANLEF-UHFFFAOYSA-N 5-chloro-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound OC(=O)C1=CC(Cl)=CC2=C1OCC2 SGPAPRPKRANLEF-UHFFFAOYSA-N 0.000 description 2
- BPKFAPZPAZSNPV-UHFFFAOYSA-N 5-ethylsulfonyl-2-methyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound OC(=O)C1=CC(S(=O)(=O)CC)=CC2=C1OC(C)C2 BPKFAPZPAZSNPV-UHFFFAOYSA-N 0.000 description 2
- AFOVEAQMIPOAHV-UHFFFAOYSA-N 5-methyl-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound O1CCCC2=C1C(C(O)=O)=CC=C2C AFOVEAQMIPOAHV-UHFFFAOYSA-N 0.000 description 2
- WCOVSVDZHFFOSC-UHFFFAOYSA-N 6-(cyclopropylmethyl)-3,4-dihydro-2h-thiochromene-8-carboxylic acid Chemical compound C=1C=2CCCSC=2C(C(=O)O)=CC=1CC1CC1 WCOVSVDZHFFOSC-UHFFFAOYSA-N 0.000 description 2
- YUGUBALHDJSUMT-UHFFFAOYSA-N 6-(methylsulfamoyl)-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound C1CCOC2=C1C=C(S(=O)(=O)NC)C=C2C(O)=O YUGUBALHDJSUMT-UHFFFAOYSA-N 0.000 description 2
- HIDAFWCPNYVJAD-UHFFFAOYSA-N 6-chloro-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound C1CCOC2=C1C=C(Cl)C=C2C(=O)O HIDAFWCPNYVJAD-UHFFFAOYSA-N 0.000 description 2
- XBRJTRHVGGRYID-UHFFFAOYSA-N 6-chloro-n-[[1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methyl]-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C=1C(Cl)=CC=2CCCOC=2C=1C(=O)NCC1CCCN1CC1=CCCCC1 XBRJTRHVGGRYID-UHFFFAOYSA-N 0.000 description 2
- NAWOZGJWOAYPIV-UHFFFAOYSA-N 6-chlorosulfonyl-5-methyl-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound C1CCOC2=C(C(O)=O)C=C(S(Cl)(=O)=O)C(C)=C21 NAWOZGJWOAYPIV-UHFFFAOYSA-N 0.000 description 2
- WOISHLGVPHAEDA-UHFFFAOYSA-N 6-ethylsulfonyl-5-methyl-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound O1CCCC2=C(C)C(S(=O)(=O)CC)=CC(C(O)=O)=C21 WOISHLGVPHAEDA-UHFFFAOYSA-N 0.000 description 2
- GIBFKPSXYYCRPS-UHFFFAOYSA-N 6-sulfanyl-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound C1CCOC2=C1C=C(S)C=C2C(=O)O GIBFKPSXYYCRPS-UHFFFAOYSA-N 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- 239000004342 Benzoyl peroxide Substances 0.000 description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 206010022998 Irritability Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 238000007112 amidation reaction Methods 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 229940101006 anhydrous sodium sulfite Drugs 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- AFAXGSQYZLGZPG-UHFFFAOYSA-L ethane-1,2-disulfonate Chemical compound [O-]S(=O)(=O)CCS([O-])(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-L 0.000 description 2
- DSGUSEBCDAKBCM-UHFFFAOYSA-N ethane-1,2-disulfonic acid;dihydrate Chemical compound O.O.OS(=O)(=O)CCS(O)(=O)=O DSGUSEBCDAKBCM-UHFFFAOYSA-N 0.000 description 2
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- WWRFRRUCQNLZBW-UHFFFAOYSA-N methyl 2-hydroxy-4-methyl-3-prop-2-enylbenzoate Chemical compound COC(=O)C1=CC=C(C)C(CC=C)=C1O WWRFRRUCQNLZBW-UHFFFAOYSA-N 0.000 description 2
- ZLLYFBIYPGDGGJ-UHFFFAOYSA-N methyl 4-acetamido-3-(3-bromopropyl)-2-hydroxybenzoate Chemical compound COC(=O)C1=CC=C(NC(C)=O)C(CCCBr)=C1O ZLLYFBIYPGDGGJ-UHFFFAOYSA-N 0.000 description 2
- SKTAEWIUWOCYCD-UHFFFAOYSA-N methyl 4-bromo-2-hydroxy-3-prop-2-enylbenzoate Chemical compound COC(=O)C1=CC=C(Br)C(CC=C)=C1O SKTAEWIUWOCYCD-UHFFFAOYSA-N 0.000 description 2
- JEMVEVUWSJXZMX-UHFFFAOYSA-N methyl 4-bromo-2-hydroxybenzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1O JEMVEVUWSJXZMX-UHFFFAOYSA-N 0.000 description 2
- YBTQUOABZWFEGO-UHFFFAOYSA-N methyl 4-methyl-2-prop-2-enoxybenzoate Chemical compound COC(=O)C1=CC=C(C)C=C1OCC=C YBTQUOABZWFEGO-UHFFFAOYSA-N 0.000 description 2
- QUGQJQKLRQWWRD-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-5-ethylsulfonyl-4-methoxy-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide;hydrochloride Chemical compound Cl.CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)CC)=C(OC)C2=C1OC(C)C2 QUGQJQKLRQWWRD-UHFFFAOYSA-N 0.000 description 2
- XIAQTKONUJUJAB-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-6-ethylsulfonyl-5-methyl-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)CC)=C(C)C2=C1OCCC2 XIAQTKONUJUJAB-UHFFFAOYSA-N 0.000 description 2
- XGXIYBAHFAGGRU-UHFFFAOYSA-N n-[[1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methyl]-2-methyl-5-(methylsulfamoyl)-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound C=1C(S(=O)(=O)NC)=CC=2CC(C)OC=2C=1C(=O)NCC1CCCN1CC1=CCCCC1 XGXIYBAHFAGGRU-UHFFFAOYSA-N 0.000 description 2
- DGXRDXCERKHGHV-UHFFFAOYSA-N n-[[1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methyl]-5-(cyclopropylmethylsulfonyl)-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound C=12OC(C)CC2=CC(S(=O)(=O)CC2CC2)=CC=1C(=O)NCC1CCCN1CC1=CCCCC1 DGXRDXCERKHGHV-UHFFFAOYSA-N 0.000 description 2
- XFOSLLKUFTXGDS-UHFFFAOYSA-N n-[[1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methyl]-6-(methylsulfamoyl)-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C=1C(S(=O)(=O)NC)=CC=2CCCOC=2C=1C(=O)NCC1CCCN1CC1=CCCCC1 XFOSLLKUFTXGDS-UHFFFAOYSA-N 0.000 description 2
- FMLJYMXKZJHZIN-UHFFFAOYSA-N n-[[1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-5-ethylsulfonyl-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide;hydrochloride Chemical compound Cl.C=1C(S(=O)(=O)CC)=CC=2CC(C)OC=2C=1C(=O)NCC1CCCN1CC1CC1 FMLJYMXKZJHZIN-UHFFFAOYSA-N 0.000 description 2
- ROLSLQXAZBRPOA-UHFFFAOYSA-N n-[[1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-6-ethylsulfonyl-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C=1C(S(=O)(=O)CC)=CC=2CCCOC=2C=1C(=O)NCC1CCCN1CC1CC1 ROLSLQXAZBRPOA-UHFFFAOYSA-N 0.000 description 2
- 230000000701 neuroleptic effect Effects 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
- 239000004296 sodium metabisulphite Substances 0.000 description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 229940001482 sodium sulfite Drugs 0.000 description 2
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
- UHXBMSNEECJPSX-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1OCC2 UHXBMSNEECJPSX-UHFFFAOYSA-N 0.000 description 1
- ATGSLQBVSZNJMT-UHFFFAOYSA-N 2,5-dichloropentan-1-amine;hydrochloride Chemical compound Cl.NCC(Cl)CCCCl ATGSLQBVSZNJMT-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
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- 229940093475 2-ethoxyethanol Drugs 0.000 description 1
- JDVYEAYUSLIUHX-UHFFFAOYSA-N 2-ethyl-1-methylpyrrolidin-2-amine Chemical compound CCC1(N)CCCN1C JDVYEAYUSLIUHX-UHFFFAOYSA-N 0.000 description 1
- GBGBIIDMPLANTO-UHFFFAOYSA-N 2-methyl-2,3-dihydro-1-benzofuran-7-carbonyl chloride Chemical compound C1=CC(C(Cl)=O)=C2OC(C)CC2=C1 GBGBIIDMPLANTO-UHFFFAOYSA-N 0.000 description 1
- ODPUQXPBOSLFOO-UHFFFAOYSA-N 2-methyl-5-(methylsulfamoyl)-2,3-dihydro-1-benzofuran-7-carbonyl chloride Chemical compound ClC(=O)C1=CC(S(=O)(=O)NC)=CC2=C1OC(C)C2 ODPUQXPBOSLFOO-UHFFFAOYSA-N 0.000 description 1
- DVURTEWCGPFUBO-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C2=C1OC(C)C2 DVURTEWCGPFUBO-UHFFFAOYSA-N 0.000 description 1
- DLSGTAJLCDZBJF-UHFFFAOYSA-N 4-methoxy-2-methyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound COC1=CC=C(C(O)=O)C2=C1CC(C)O2 DLSGTAJLCDZBJF-UHFFFAOYSA-N 0.000 description 1
- KPRWPAVXFHNNHY-UHFFFAOYSA-N 5-(cyclopropylmethylsulfanyl)-2-methyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound C=1C(C(O)=O)=C2OC(C)CC2=CC=1SCC1CC1 KPRWPAVXFHNNHY-UHFFFAOYSA-N 0.000 description 1
- ZTGYYMNIVDBVRY-UHFFFAOYSA-N 5-(cyclopropylmethylsulfonyl)-n-[(1-ethylpyrrolidin-2-yl)methyl]-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)CC2CC2)=CC2=C1OC(C)C2 ZTGYYMNIVDBVRY-UHFFFAOYSA-N 0.000 description 1
- QERQYAAEZTXMCX-UHFFFAOYSA-N 5-amino-6-ethylsulfonyl-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound O1CCCC2=C(N)C(S(=O)(=O)CC)=CC(C(O)=O)=C21 QERQYAAEZTXMCX-UHFFFAOYSA-N 0.000 description 1
- UCWRUKVGDLBXAB-UHFFFAOYSA-N 5-amino-n-[[1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-6-(methylsulfamoyl)-3,4-dihydro-2h-chromene-8-carboxamide;hydrochloride Chemical compound Cl.C=12OCCCC2=C(N)C(S(=O)(=O)NC)=CC=1C(=O)NCC1CCCN1CC1CC1 UCWRUKVGDLBXAB-UHFFFAOYSA-N 0.000 description 1
- YIYMIUAFLOAZGG-UHFFFAOYSA-N 5-chloro-n-[[1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methyl]-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound C=12OC(C)CC2=CC(Cl)=CC=1C(=O)NCC1CCCN1CC1=CCCCC1 YIYMIUAFLOAZGG-UHFFFAOYSA-N 0.000 description 1
- IJMZGXWLELXQOL-UHFFFAOYSA-N 5-chlorosulfonyl-4-methoxy-2-methyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound C1=C(S(Cl)(=O)=O)C(OC)=C2CC(C)OC2=C1C(O)=O IJMZGXWLELXQOL-UHFFFAOYSA-N 0.000 description 1
- OWWPIKBFOLAMAN-UHFFFAOYSA-N 5-ethylsulfonyl-4-methoxy-2-methyl-2,3-dihydro-1-benzofuran Chemical compound C(C)S(=O)(=O)C=1C=CC2=C(CC(O2)C)C=1OC OWWPIKBFOLAMAN-UHFFFAOYSA-N 0.000 description 1
- NBFBKENIEVTKNL-UHFFFAOYSA-N 5-ethylsulfonyl-4-methoxy-2-methyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound CCS(=O)(=O)C1=CC(C(O)=O)=C2OC(C)CC2=C1OC NBFBKENIEVTKNL-UHFFFAOYSA-N 0.000 description 1
- LZUIPOCVOKUROL-UHFFFAOYSA-N 6-(cyclopropylmethylsulfonyl)-n-[(1-ethylpyrrolidin-2-yl)methyl]-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)CC2CC2)=CC2=C1OCCC2 LZUIPOCVOKUROL-UHFFFAOYSA-N 0.000 description 1
- KPQIWYXPCLLEIJ-UHFFFAOYSA-N 6-chloro-3,4-dihydro-2h-chromene Chemical compound O1CCCC2=CC(Cl)=CC=C21 KPQIWYXPCLLEIJ-UHFFFAOYSA-N 0.000 description 1
- AQRHWJYTYSGIOK-UHFFFAOYSA-N 6-chloro-3,4-dihydro-2h-chromene-8-carbonyl chloride Chemical compound C1CCOC2=C1C=C(Cl)C=C2C(=O)Cl AQRHWJYTYSGIOK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- HTGKTSVPJJNEMQ-QMMMGPOBSA-N [(2s)-1-prop-2-enylpyrrolidin-2-yl]methanamine Chemical compound NC[C@@H]1CCCN1CC=C HTGKTSVPJJNEMQ-QMMMGPOBSA-N 0.000 description 1
- BCXIHNPGQKJBMF-UHFFFAOYSA-N [1-(cyclohexylmethyl)pyrrolidin-2-yl]methanamine Chemical compound NCC1CCCN1CC1CCCCC1 BCXIHNPGQKJBMF-UHFFFAOYSA-N 0.000 description 1
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 229910001431 copper ion Inorganic materials 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- 229960003280 cupric chloride Drugs 0.000 description 1
- 229940045803 cuprous chloride Drugs 0.000 description 1
- AYQJCDBGGILQIZ-UHFFFAOYSA-N cyclohexen-1-ylmethanamine Chemical compound NCC1=CCCCC1 AYQJCDBGGILQIZ-UHFFFAOYSA-N 0.000 description 1
- WRPMREPGSFVNAQ-UHFFFAOYSA-N cyclopropylmethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1CC1 WRPMREPGSFVNAQ-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- UITFCFWKYAOJEJ-UHFFFAOYSA-N methyl 2-hydroxy-4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C=C1O UITFCFWKYAOJEJ-UHFFFAOYSA-N 0.000 description 1
- WPIUICUWBBLVAJ-UHFFFAOYSA-N methyl 4-acetamido-2-hydroxy-3-prop-2-enylbenzoate Chemical compound COC(=O)C1=CC=C(NC(C)=O)C(CC=C)=C1O WPIUICUWBBLVAJ-UHFFFAOYSA-N 0.000 description 1
- LCXHOHRQXZMSQN-UHFFFAOYSA-N methyl 4-acetamido-2-hydroxybenzoate Chemical compound COC(=O)C1=CC=C(NC(C)=O)C=C1O LCXHOHRQXZMSQN-UHFFFAOYSA-N 0.000 description 1
- ABFGWYPYKMCEDC-UHFFFAOYSA-N methyl 4-acetamido-3-(3-bromopropyl)-5-chloro-2-hydroxybenzoate Chemical compound COC(=O)C1=CC(Cl)=C(NC(C)=O)C(CCCBr)=C1O ABFGWYPYKMCEDC-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- MKDYQLJYEBWUIG-UHFFFAOYSA-N n',n'-diethyl-n-methylethane-1,2-diamine Chemical compound CCN(CC)CCNC MKDYQLJYEBWUIG-UHFFFAOYSA-N 0.000 description 1
- GJZAXHCGEJGCKG-UHFFFAOYSA-N n-(2,5-dichloropentyl)-6-ethylsulfonyl-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C1CCOC2=C1C=C(S(=O)(=O)CC)C=C2C(=O)NCC(Cl)CCCCl GJZAXHCGEJGCKG-UHFFFAOYSA-N 0.000 description 1
- XRSGROYAHHYBQX-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound CCN1CCCC1CNC(=O)C1=CC=CC2=C1OCCC2 XRSGROYAHHYBQX-UHFFFAOYSA-N 0.000 description 1
- SEGNASMWALWFFW-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-5-ethylsulfonyl-4-methoxy-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)CC)=C(OC)C2=C1OC(C)C2 SEGNASMWALWFFW-UHFFFAOYSA-N 0.000 description 1
- VOOZZNJPDWKHMO-UHFFFAOYSA-N n-[[1-(cyclohexen-1-ylmethyl)pyrrolidin-2-yl]methyl]-5-(cyclopropylmethylsulfonyl)-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.C=12OC(C)CC2=CC(S(=O)(=O)CC2CC2)=CC=1C(=O)NCC1CCCN1CC1=CCCCC1 VOOZZNJPDWKHMO-UHFFFAOYSA-N 0.000 description 1
- STOOEPYBPULNTR-UHFFFAOYSA-N n-[[1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-6-(cyclopropylmethylsulfonyl)-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C=1C(S(=O)(=O)CC2CC2)=CC=2CCCOC=2C=1C(=O)NCC1CCCN1CC1CC1 STOOEPYBPULNTR-UHFFFAOYSA-N 0.000 description 1
- DLIFJJJTIASJQU-UHFFFAOYSA-N n-[[1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-6-ethylsulfonyl-3,4-dihydro-2h-chromene-8-carboxamide;hydrochloride Chemical compound Cl.C=1C(S(=O)(=O)CC)=CC=2CCCOC=2C=1C(=O)NCC1CCCN1CC1CC1 DLIFJJJTIASJQU-UHFFFAOYSA-N 0.000 description 1
- IQNCFOOPRZLWKT-UHFFFAOYSA-N n-[[1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-6-ethylsulfonyl-5-methyl-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C=12OCCCC2=C(C)C(S(=O)(=O)CC)=CC=1C(=O)NCC1CCCN1CC1CC1 IQNCFOOPRZLWKT-UHFFFAOYSA-N 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- QQOXBFUTRLDXDP-UHFFFAOYSA-N p-Aminosalicylic acid methyl ester Chemical compound COC(=O)C1=CC=C(N)C=C1O QQOXBFUTRLDXDP-UHFFFAOYSA-N 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical compound [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrane Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Medicinal Preparation (AREA)
- Furan Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Polyamides (AREA)
- Peptides Or Proteins (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS88362A CS264300B2 (cs) | 1986-01-30 | 1988-01-19 | Způsob výroby nových dihydrobenzcfuran- a -ehroman-karboxamidů |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8601279A FR2593504B1 (fr) | 1986-01-30 | 1986-01-30 | Nouveaux derives de dihydrobenzofuranne - et de chromane - carboxamides, leurs procedes de preparation et leur utilisation comme neuroleptiques |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS57887A2 CS57887A2 (en) | 1988-09-16 |
| CS264288B2 true CS264288B2 (en) | 1989-06-13 |
Family
ID=9331629
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS87578A CS264288B2 (en) | 1986-01-30 | 1987-01-29 | Process for preparing new dihydrobenzofuran- and chromat-carboxamides |
| CS88362A CS264300B2 (cs) | 1986-01-30 | 1988-01-19 | Způsob výroby nových dihydrobenzcfuran- a -ehroman-karboxamidů |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS88362A CS264300B2 (cs) | 1986-01-30 | 1988-01-19 | Způsob výroby nových dihydrobenzcfuran- a -ehroman-karboxamidů |
Country Status (40)
| Country | Link |
|---|---|
| US (1) | US5006570A (xx) |
| EP (1) | EP0231139B1 (xx) |
| JP (1) | JPS62277376A (xx) |
| KR (1) | KR870007160A (xx) |
| CN (2) | CN1016420B (xx) |
| AT (1) | ATE70063T1 (xx) |
| AU (1) | AU593605B2 (xx) |
| BE (1) | BE1000164A5 (xx) |
| BG (1) | BG46600A3 (xx) |
| CA (1) | CA1300161C (xx) |
| CH (1) | CH670827A5 (xx) |
| CS (2) | CS264288B2 (xx) |
| DD (1) | DD260065A5 (xx) |
| DE (2) | DE3702005A1 (xx) |
| DK (1) | DK46987A (xx) |
| ES (2) | ES2003671A6 (xx) |
| FI (1) | FI870347A (xx) |
| FR (1) | FR2593504B1 (xx) |
| GB (1) | GB2187188B (xx) |
| GR (2) | GR870134B (xx) |
| HU (1) | HU206107B (xx) |
| IE (1) | IE870128L (xx) |
| IL (1) | IL81299A (xx) |
| IN (2) | IN164389B (xx) |
| IS (1) | IS1446B6 (xx) |
| IT (1) | IT1205729B (xx) |
| LU (1) | LU86747A1 (xx) |
| MA (1) | MA20861A1 (xx) |
| NO (1) | NO168582C (xx) |
| NZ (1) | NZ219068A (xx) |
| OA (1) | OA08472A (xx) |
| PH (1) | PH23392A (xx) |
| PL (2) | PL152404B1 (xx) |
| PT (1) | PT84224B (xx) |
| SU (2) | SU1609451A3 (xx) |
| TN (1) | TNSN87012A1 (xx) |
| YU (1) | YU46185B (xx) |
| ZA (1) | ZA87552B (xx) |
| ZM (1) | ZM987A1 (xx) |
| ZW (1) | ZW1387A1 (xx) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2611715B1 (fr) * | 1987-02-27 | 1989-05-12 | Adir | Nouveaux acetamides derives de la dihydro-2,3 phenyl-3 benzofurannone-2, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent |
| FR2611713B1 (fr) * | 1987-02-27 | 1990-11-30 | Adir | Nouveaux derives de l'acide (dihydro-2,3 oxo-2 benzofurannyl-3)-2 acetique, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent |
| US5374637A (en) * | 1989-03-22 | 1994-12-20 | Janssen Pharmaceutica N.V. | N-(3-hydroxy-4-piperidinyl)(dihydrobenzofuran, dihydro-2H-benzopyran or dihydrobenzodioxin)carboxamide derivatives |
| JP2726306B2 (ja) * | 1989-04-14 | 1998-03-11 | 本田技研工業株式会社 | 車両の前後輪操舵装置 |
| US5122361A (en) * | 1989-04-17 | 1992-06-16 | Trustees Of The University Of Pennsylvania | Dopamine receptor ligands and imaging agents |
| EP0412939A3 (en) * | 1989-08-11 | 1991-09-04 | Ciba-Geigy Ag | Certain benzopyran and benzothiopyran derivatives |
| US5616610A (en) * | 1989-12-22 | 1997-04-01 | Astra Aktiebolag | (R)-5-carbamoyl-8-fluoro-3-N,N-disubstituted-amino-3,4-dihydro-2H-1-benzopyrans |
| US5420151A (en) * | 1989-12-22 | 1995-05-30 | Aktiebolaget Astra | Chroman derivatives |
| GB9005014D0 (en) * | 1990-03-06 | 1990-05-02 | Janssen Pharmaceutica Nv | N.(4.piperidinyl)(dihydrobenzofuran or dihydro.2h.benzopyran)carboxamide derivatives |
| WO1991017144A1 (en) * | 1990-05-02 | 1991-11-14 | Yoshitomi Pharmaceutical Industries, Ltd. | Amide compound, pharmaceutical use thereof and novel 1-substituted pyrrolidinemethyl-amines |
| US5114947A (en) * | 1990-12-27 | 1992-05-19 | Erbamont Inc. | Method for alleviating anxiety using benzobicyclic carboxamides |
| MA22647A1 (fr) * | 1991-09-14 | 1993-04-01 | Smithkline Beecham Plc | Procede de preparation d'un ester ou d'un amide d'un nouveau produit . |
| EP0625149A1 (en) * | 1992-02-06 | 1994-11-23 | Smithkline Beecham Plc | Benzopyran, benzothiopyran and benzofuran derivatives as 5-ht4 antagonists |
| AU5150393A (en) * | 1992-10-13 | 1994-05-09 | Smithkline Beecham Plc | Heterocyclic -esters or -amides used as 5-ht4 receptor antagonists |
| US6127379A (en) * | 1993-02-01 | 2000-10-03 | Smithkline Beecham P.L.C. | Benzopyran, benzothiopyran and benzofuran derivatives as 5-HT4 antagonists |
| JP2999669B2 (ja) * | 1993-08-24 | 2000-01-17 | 株式会社三和化学研究所 | ベンゾ［ｂ］フランカルボキサミド誘導体、その製法及び用途 |
| JPH0820586A (ja) * | 1994-07-05 | 1996-01-23 | Sanwa Kagaku Kenkyusho Co Ltd | １−アザビシクロ［３．３．０］オクタン誘導体、その塩及び製法並びに用途 |
| JPH0873463A (ja) | 1994-07-05 | 1996-03-19 | Sanwa Kagaku Kenkyusho Co Ltd | ベンゾピランカルボキサミド誘導体、その塩及び製法並びに用途 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0135545A1 (en) * | 1983-02-19 | 1985-04-03 | Beecham Group Plc | Azabicycloalkyl benzamide and anilide derivatives |
| JPS59186969A (ja) * | 1983-04-08 | 1984-10-23 | Yoshitomi Pharmaceut Ind Ltd | ベンゾフラン−およびベンゾピランカルボキサミド誘導体 |
| CA1297877C (en) * | 1983-12-22 | 1992-03-24 | Daniel Lednicer | Benzofurancarboxamides useful as antiemetic or antipsychotic agents |
| JPS63139180A (ja) * | 1986-12-02 | 1988-06-10 | Tanabe Seiyaku Co Ltd | カルボン酸誘導体 |
-
1986
- 1986-01-30 FR FR8601279A patent/FR2593504B1/fr not_active Expired
-
1987
- 1987-01-16 NO NO870199A patent/NO168582C/no unknown
- 1987-01-19 IL IL81299A patent/IL81299A/xx not_active IP Right Cessation
- 1987-01-20 IE IE870128A patent/IE870128L/xx unknown
- 1987-01-21 IN IN43/MAS/87A patent/IN164389B/en unknown
- 1987-01-21 AU AU67855/87A patent/AU593605B2/en not_active Ceased
- 1987-01-21 IS IS3189A patent/IS1446B6/is unknown
- 1987-01-23 DE DE19873702005 patent/DE3702005A1/de not_active Withdrawn
- 1987-01-23 ZW ZW13/87A patent/ZW1387A1/xx unknown
- 1987-01-26 ZA ZA87552A patent/ZA87552B/xx unknown
- 1987-01-27 GR GR870134A patent/GR870134B/el unknown
- 1987-01-27 FI FI870347A patent/FI870347A/fi not_active Application Discontinuation
- 1987-01-27 MA MA21095A patent/MA20861A1/fr unknown
- 1987-01-27 YU YU11387A patent/YU46185B/sh unknown
- 1987-01-27 NZ NZ219068A patent/NZ219068A/en unknown
- 1987-01-28 GB GB8701870A patent/GB2187188B/en not_active Expired
- 1987-01-28 CA CA000528418A patent/CA1300161C/fr not_active Expired - Lifetime
- 1987-01-28 KR KR870000673A patent/KR870007160A/ko not_active Application Discontinuation
- 1987-01-28 BG BG78228A patent/BG46600A3/xx active Active
- 1987-01-28 LU LU86747A patent/LU86747A1/fr unknown
- 1987-01-28 TN TNTNSN87012A patent/TNSN87012A1/fr unknown
- 1987-01-28 CN CN87100978A patent/CN1016420B/zh not_active Expired
- 1987-01-29 AT AT87400194T patent/ATE70063T1/de not_active IP Right Cessation
- 1987-01-29 ES ES8700216A patent/ES2003671A6/es not_active Expired
- 1987-01-29 SU SU874028919A patent/SU1609451A3/ru active
- 1987-01-29 PH PH34786A patent/PH23392A/en unknown
- 1987-01-29 CS CS87578A patent/CS264288B2/cs unknown
- 1987-01-29 IT IT47583/87A patent/IT1205729B/it active
- 1987-01-29 ES ES198787400194T patent/ES2038679T3/es not_active Expired - Lifetime
- 1987-01-29 EP EP87400194A patent/EP0231139B1/fr not_active Expired - Lifetime
- 1987-01-29 DK DK046987A patent/DK46987A/da unknown
- 1987-01-29 HU HU87283A patent/HU206107B/hu not_active IP Right Cessation
- 1987-01-29 DD DD87299591A patent/DD260065A5/de unknown
- 1987-01-29 PT PT84224A patent/PT84224B/pt not_active IP Right Cessation
- 1987-01-29 DE DE8787400194T patent/DE3774888D1/de not_active Expired - Lifetime
- 1987-01-29 OA OA59056A patent/OA08472A/xx unknown
- 1987-01-29 CH CH300/87A patent/CH670827A5/fr not_active IP Right Cessation
- 1987-01-29 ZM ZM9/87A patent/ZM987A1/xx unknown
- 1987-01-30 US US07/008,916 patent/US5006570A/en not_active Expired - Fee Related
- 1987-01-30 BE BE8700065A patent/BE1000164A5/fr not_active Expired
- 1987-01-30 PL PL1987263885A patent/PL152404B1/pl unknown
- 1987-01-30 PL PL1987272298A patent/PL152491B1/pl unknown
- 1987-01-30 JP JP62021649A patent/JPS62277376A/ja active Pending
-
1988
- 1988-01-19 CS CS88362A patent/CS264300B2/cs unknown
- 1988-05-23 IN IN343/MAS/88A patent/IN167060B/en unknown
- 1988-06-28 SU SU884355973A patent/SU1607688A3/ru active
-
1992
- 1992-01-04 CN CN92100139A patent/CN1062144A/zh active Pending
- 1992-01-27 GR GR920400082T patent/GR3003653T3/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CS264288B2 (en) | Process for preparing new dihydrobenzofuran- and chromat-carboxamides | |
| RU2155187C2 (ru) | Производные индола, их таутомеры, смеси их изомеров или отдельные изомеры и фармацевтически приемлемые соли, фармацевтическая композиция с антиопухолевой или ингибирующей протеин-тирозинкиназу активностью и способ торможения зависящего от протеин-тирозинкиназы заболевания или борьбы с аберрантным ростом клеток млекопитающего или человека. | |
| SK100794A3 (en) | Heterocyclic compounds | |
| CZ288527B6 (cs) | Derivát benzofuranu, benzothiofenu, indolu nebo indolizinu, způsob jejich přípravy, jejich použití a farmaceutický prostředek, který je obsahuje | |
| CS201040B2 (en) | Method of producing etherified hydroxy-benzo-diheterocyclic compounds | |
| MX2008011615A (es) | Derivados de acidos carboxilicos biciclicos utiles para tratar trastornos metabolicos. | |
| CA2415847C (fr) | Aminoalkylbenzoyl-benzofuranes ou benzothiophenes, leur procede de preparation et les compositions les contenant | |
| HU214032B (en) | Process for producing benzoisothiazole and benzoisoxazole-3-carboxamide derivatives and pharmaceutical compositions comprising such compounds as active ingredient | |
| KR900001313B1 (ko) | 4h-1-벤조피란-4-온 및 그 제조방법 | |
| AU2005331482B2 (en) | Dihydropyridine derivatives | |
| KR20090122931A (ko) | 오르니틴 유도체 | |
| HU184797B (en) | Process for preparing quinazoline derivatives | |
| KR20100083195A (ko) | 신규한 디아제니움디올레이트 유도체, 이들의 제조 방법 및 상기 화합물을 포함하는 약제 조성물 | |
| EP0150505B1 (en) | 3-indolecarboxamide compounds | |
| KR19990077308A (ko) | 퀴놀린-2-(1h)-온 | |
| FR2642755A1 (xx) | ||
| US6184245B1 (en) | Cyclic ketone derivatives and their medical applications | |
| US6156793A (en) | Prophylactic/therapeutic agents for atherosclerosis | |
| JP5474548B2 (ja) | 治療用の置換チアゾリジノン類、オキサゾリジノン類および関連化合物 | |
| FR2551753A2 (fr) | Benzotriazine-1,2,3-ones-4, procede de preparation et medicaments les contenant | |
| DK168072B1 (da) | 5-(2-(pyrrolidin-1-yl)ethoxy)-p-cymenderivater, fremgangsmaade til fremstilling deraf samt laegemidler indeholdende disse | |
| RU2198881C2 (ru) | α-(1-ПИПЕРАЗИНИЛ)АЦЕТАМИДОПРОИЗВОДНЫЕ АРЕНКАРБОНОВОЙ КИСЛОТЫ, СПОСОБ ИХ ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ, СПОСОБЫ ЛЕЧЕНИЯ | |
| JPH10512553A (ja) | 新規な化合物 | |
| AU3585399A (en) | Intermediates for the preparation of therapeutic amides | |
| FR2672599A1 (fr) | Derives de benzothiazepine-1,5, leur preparation et leur application en therapeutique. |