JPH04993B2 - - Google Patents
Info
- Publication number
- JPH04993B2 JPH04993B2 JP58015097A JP1509783A JPH04993B2 JP H04993 B2 JPH04993 B2 JP H04993B2 JP 58015097 A JP58015097 A JP 58015097A JP 1509783 A JP1509783 A JP 1509783A JP H04993 B2 JPH04993 B2 JP H04993B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- thiopyrano
- dihydro
- pyrimidine
- piperazino
- 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
- -1 hydroxyethylamino group Chemical group 0.000 claims description 43
- 150000001875 compounds Chemical class 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 125000003277 amino group Chemical group 0.000 claims description 7
- PHQVXPYZZSPBHC-UHFFFAOYSA-N 6h-thiopyrano[3,2-d]pyrimidine Chemical class N1=CN=C2C=CCSC2=C1 PHQVXPYZZSPBHC-UHFFFAOYSA-N 0.000 claims description 6
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 6
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 239000013078 crystal Substances 0.000 description 47
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 46
- 238000002844 melting Methods 0.000 description 46
- 230000008018 melting Effects 0.000 description 46
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 14
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 7
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- DGEYTDCFMQMLTH-UHFFFAOYSA-N methanol;propan-2-ol Chemical compound OC.CC(C)O DGEYTDCFMQMLTH-UHFFFAOYSA-N 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- ZRSGSXGGDIEONU-SPIKMXEPSA-N (Z)-but-2-enedioic acid 4-piperazin-1-yl-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidin-2-amine Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.N=1C(N)=NC=2CCCSC=2C=1N1CCNCC1 ZRSGSXGGDIEONU-SPIKMXEPSA-N 0.000 description 4
- HIKOVOQFJFSCLL-UHFFFAOYSA-N 2,4-dichloro-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidine Chemical compound S1CCCC2=NC(Cl)=NC(Cl)=C21 HIKOVOQFJFSCLL-UHFFFAOYSA-N 0.000 description 4
- BYDDYIAAWSEFJA-UHFFFAOYSA-N 4-chloro-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-2-amine Chemical compound S1CCCC2=NC(N)=NC(Cl)=C21 BYDDYIAAWSEFJA-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 4
- HIMXGTXNXJYFGB-UHFFFAOYSA-N alloxan Chemical compound O=C1NC(=O)C(=O)C(=O)N1 HIMXGTXNXJYFGB-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000013076 target substance Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical class C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 3
- 150000002688 maleic acid derivatives Chemical class 0.000 description 3
- NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
- MSSDTZLYNMFTKN-UHFFFAOYSA-N 1-Piperazinecarboxaldehyde Chemical compound O=CN1CCNCC1 MSSDTZLYNMFTKN-UHFFFAOYSA-N 0.000 description 2
- OVSRTBOZBHONQW-UHFFFAOYSA-N 2-amino-1,6,7,8-tetrahydrothiopyrano[3,2-d]pyrimidin-4-one Chemical compound S1CCCC2=NC(N)=NC(O)=C21 OVSRTBOZBHONQW-UHFFFAOYSA-N 0.000 description 2
- YVIZUDQMKQIGCZ-UHFFFAOYSA-N 2-chloro-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-4-amine Chemical compound C1CCSC2=C1N=C(Cl)N=C2N YVIZUDQMKQIGCZ-UHFFFAOYSA-N 0.000 description 2
- KMPUACMJNGJZDJ-UHFFFAOYSA-N 2-piperazin-1-yl-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-4-amine Chemical compound N=1C=2CCCSC=2C(N)=NC=1N1CCNCC1 KMPUACMJNGJZDJ-UHFFFAOYSA-N 0.000 description 2
- CQXAAPQFTXYFOR-UHFFFAOYSA-N 4-(2-chloro-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-4-yl)piperazine-1-carbaldehyde Chemical compound N=1C(Cl)=NC=2CCCSC=2C=1N1CCN(C=O)CC1 CQXAAPQFTXYFOR-UHFFFAOYSA-N 0.000 description 2
- TWZICWNVVMBLJZ-UHFFFAOYSA-N 4-(2-morpholin-4-yl-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-4-yl)piperazine-1-carbaldehyde Chemical compound C1CN(C=O)CCN1C1=NC(N2CCOCC2)=NC2=C1SCCC2 TWZICWNVVMBLJZ-UHFFFAOYSA-N 0.000 description 2
- LCLDBDPNEUHPCS-UHFFFAOYSA-N 4-(2-piperidin-1-yl-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-4-yl)piperazine-1-carbaldehyde Chemical compound C1CN(C=O)CCN1C1=NC(N2CCCCC2)=NC2=C1SCCC2 LCLDBDPNEUHPCS-UHFFFAOYSA-N 0.000 description 2
- GKEKTQPBVLFOMV-UHFFFAOYSA-N 4-piperazin-1-yl-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-2-amine Chemical compound N=1C(N)=NC=2CCCSC=2C=1N1CCNCC1 GKEKTQPBVLFOMV-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical class C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000002218 hypoglycaemic effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- JWHDSQLZFBJWKA-UHFFFAOYSA-N n,n-dimethyl-4-piperazin-1-yl-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-2-amine Chemical compound N=1C(N(C)C)=NC=2CCCSC=2C=1N1CCNCC1 JWHDSQLZFBJWKA-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- RHIMGBOHIJKSFW-SPIKMXEPSA-N (z)-but-2-enedioic acid;n-methyl-4-piperazin-1-yl-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-2-amine Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.N=1C(NC)=NC=2CCCSC=2C=1N1CCNCC1 RHIMGBOHIJKSFW-SPIKMXEPSA-N 0.000 description 1
- VPXHNCJNSBHLJK-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-4-amine Chemical compound C1CN(C)CCN1C1=NC(N)=C(SCCC2)C2=N1 VPXHNCJNSBHLJK-UHFFFAOYSA-N 0.000 description 1
- PJIIOCXBXURAMP-UHFFFAOYSA-N 2-[(2-chloro-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-4-yl)amino]ethanol Chemical compound C1CCSC2=C1N=C(Cl)N=C2NCCO PJIIOCXBXURAMP-UHFFFAOYSA-N 0.000 description 1
- NYCXKEFZVRNFML-UHFFFAOYSA-N 2-chloro-4-(4-methylpiperazin-1-yl)-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidine Chemical compound C1CN(C)CCN1C1=NC(Cl)=NC2=C1SCCC2 NYCXKEFZVRNFML-UHFFFAOYSA-N 0.000 description 1
- HBVTZUWNRGSQHF-UHFFFAOYSA-N 4-(2-pyrrolidin-1-yl-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-4-yl)piperazine-1-carbaldehyde Chemical compound C1CN(C=O)CCN1C1=NC(N2CCCC2)=NC2=C1SCCC2 HBVTZUWNRGSQHF-UHFFFAOYSA-N 0.000 description 1
- BDOLEBSUOSLTBJ-UHFFFAOYSA-N 4-(4-benzylpiperazin-1-yl)-2-pyrrolidin-1-yl-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidine Chemical compound C=1C=CC=CC=1CN(CC1)CCN1C(C=1SCCCC=1N=1)=NC=1N1CCCC1 BDOLEBSUOSLTBJ-UHFFFAOYSA-N 0.000 description 1
- HKAKNSUNGCSAGC-UHFFFAOYSA-N 4-(4-benzylpiperazin-1-yl)-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-2-amine Chemical compound N=1C(N)=NC=2CCCSC=2C=1N(CC1)CCN1CC1=CC=CC=C1 HKAKNSUNGCSAGC-UHFFFAOYSA-N 0.000 description 1
- YYLCDUICOKVJKL-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-2-amine Chemical compound C1CN(C)CCN1C1=NC(N)=NC2=C1SCCC2 YYLCDUICOKVJKL-UHFFFAOYSA-N 0.000 description 1
- NEURQSJPJFWELW-UHFFFAOYSA-N 4-(4-piperazin-1-yl-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-2-yl)morpholine Chemical compound C1CCSC2=C1N=C(N1CCOCC1)N=C2N1CCNCC1 NEURQSJPJFWELW-UHFFFAOYSA-N 0.000 description 1
- JFOXRDNUPZODBX-UHFFFAOYSA-N 4-[4-(4-methylpiperazin-1-yl)-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-2-yl]morpholine Chemical compound C1CN(C)CCN1C1=NC(N2CCOCC2)=NC2=C1SCCC2 JFOXRDNUPZODBX-UHFFFAOYSA-N 0.000 description 1
- RRYVBVSILIRHAE-UHFFFAOYSA-N 4-[4-(methylamino)-2-methylimino-3,6,7,8-tetrahydro-1H-thiopyrano[3,2-d]pyrimidin-4-yl]piperazine-1-carbaldehyde Chemical compound CNC1(C2=C(N=C(N1)NC)CCCS2)N1CCN(CC1)C=O RRYVBVSILIRHAE-UHFFFAOYSA-N 0.000 description 1
- RFMQCCUPXBTKDU-UHFFFAOYSA-N 4-piperazin-1-yl-2-pyrrolidin-1-yl-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidine Chemical compound C1CCCN1C(N=C1N2CCNCC2)=NC2=C1SCCC2 RFMQCCUPXBTKDU-UHFFFAOYSA-N 0.000 description 1
- OMIHGPLIXGGMJB-UHFFFAOYSA-N 7-oxabicyclo[4.1.0]hepta-1,3,5-triene Chemical compound C1=CC=C2OC2=C1 OMIHGPLIXGGMJB-UHFFFAOYSA-N 0.000 description 1
- CAHQGWAXKLQREW-UHFFFAOYSA-N Benzal chloride Chemical class ClC(Cl)C1=CC=CC=C1 CAHQGWAXKLQREW-UHFFFAOYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- FYAUQRPGUUXFLL-UHFFFAOYSA-N [bromo(chloro)methyl]benzene Chemical compound ClC(Br)C1=CC=CC=C1 FYAUQRPGUUXFLL-UHFFFAOYSA-N 0.000 description 1
- DFBOAQFUHCAEAE-UHFFFAOYSA-N [chloro(fluoro)methyl]benzene Chemical compound FC(Cl)C1=CC=CC=C1 DFBOAQFUHCAEAE-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
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- STIAPHVBRDNOAJ-UHFFFAOYSA-N carbamimidoylazanium;carbonate Chemical compound NC(N)=N.NC(N)=N.OC(O)=O STIAPHVBRDNOAJ-UHFFFAOYSA-N 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- QSKWJTXWJJOJFP-UHFFFAOYSA-N chloroform;ethoxyethane Chemical compound ClC(Cl)Cl.CCOCC QSKWJTXWJJOJFP-UHFFFAOYSA-N 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- ZYBWTEQKHIADDQ-UHFFFAOYSA-N ethanol;methanol Chemical compound OC.CCO ZYBWTEQKHIADDQ-UHFFFAOYSA-N 0.000 description 1
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
- VCOKLWJRNMSWPY-UHFFFAOYSA-N ethyl 3-oxothiane-2-carboxylate Chemical compound CCOC(=O)C1SCCCC1=O VCOKLWJRNMSWPY-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- ICNZCOICHGNVLF-UHFFFAOYSA-N n-methyl-2-(4-methylpiperazin-1-yl)-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-4-amine Chemical compound N=1C=2CCCSC=2C(NC)=NC=1N1CCN(C)CC1 ICNZCOICHGNVLF-UHFFFAOYSA-N 0.000 description 1
- BDOOHLVERIWHLG-UHFFFAOYSA-N n-methyl-2-piperazin-1-yl-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-4-amine Chemical compound N=1C=2CCCSC=2C(NC)=NC=1N1CCNCC1 BDOOHLVERIWHLG-UHFFFAOYSA-N 0.000 description 1
- SNMVRZFUUCLYTO-UHFFFAOYSA-N n-propyl chloride Chemical compound CCCCl SNMVRZFUUCLYTO-UHFFFAOYSA-N 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 239000004540 pour-on Substances 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (14)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP58015097A JPS59141583A (ja) | 1983-02-01 | 1983-02-01 | チオピラノピリミジン誘導体およびその酸付加塩 |
NL8300656A NL8300656A (nl) | 1982-02-25 | 1983-02-22 | Thiopyranopyrimidineverbindingen en zuuradditiezouten daarvan. |
IT8347764A IT1212855B (it) | 1982-02-25 | 1983-02-23 | Composti tiopiranopirimidinici e loro sali di addizione ccon acidi |
CA000422274A CA1217186A (en) | 1982-02-25 | 1983-02-24 | Thiopyranopyrimidine compounds and acid addition salts thereof |
DE19833306485 DE3306485A1 (de) | 1982-02-25 | 1983-02-24 | Thiopyranopyrimidin-derivate und ihre verwendung als arzneistoffe |
ES520075A ES520075A0 (es) | 1982-02-25 | 1983-02-24 | Procedimiento de preparar compuestos tiopiranopirimidinicos farmacologicamente activos. |
GB08305175A GB2119368B (en) | 1982-02-25 | 1983-02-24 | Substituted thiopyranopyrimidine compounds |
KR1019830000757A KR840003638A (ko) | 1982-02-25 | 1983-02-24 | 치오 피라노 피리미딘 화합물의 제조 방법 및 그 산(酸)부가염 |
SE8301038A SE451135B (sv) | 1982-02-25 | 1983-02-24 | Tiopyranopyrimidinforeningar och syraadditionssalter derav |
HU83641A HU189666B (en) | 1982-02-25 | 1983-02-24 | Process for producing thiopyrano-pyrimidine derivatives and acid additional salts |
CH1077/83A CH651305A5 (de) | 1982-02-25 | 1983-02-25 | Thiopyranopyrimidin-verbindungen und deren pharmazeutisch annehmbaren saeureadditionssalze. |
FR8303183A FR2522000B1 (fr) | 1982-02-25 | 1983-02-25 | Nouvelles thiopyrannopyrimidines, utiles notamment comme agents hypoglycemiants, et leur fabrication |
US06/469,657 US4435566A (en) | 1982-02-25 | 1983-02-25 | Thiopyranopyrimidine compounds and acid addition salts thereof |
ES538649A ES8604597A1 (es) | 1982-02-25 | 1984-11-30 | Procedimiento de preparar compuestos tiopiranopirimidinicos farmacologicamente activos. |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP58015097A JPS59141583A (ja) | 1983-02-01 | 1983-02-01 | チオピラノピリミジン誘導体およびその酸付加塩 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS59141583A JPS59141583A (ja) | 1984-08-14 |
JPH04993B2 true JPH04993B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1992-01-09 |
Family
ID=11879334
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP58015097A Granted JPS59141583A (ja) | 1982-02-25 | 1983-02-01 | チオピラノピリミジン誘導体およびその酸付加塩 |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS59141583A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4898867A (en) * | 1987-09-16 | 1990-02-06 | Taiho Pharmaceutical Company, Limited | Thienopyrimidine derivaties as aldose-reductase inhibitors |
-
1983
- 1983-02-01 JP JP58015097A patent/JPS59141583A/ja active Granted
Also Published As
Publication number | Publication date |
---|---|
JPS59141583A (ja) | 1984-08-14 |
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