SE436749B - Forfarande for framstellning av 2,5-dihydro-1,2-tiazino/5,6-b/indol-3-karboxamid-1,1-dioxider - Google Patents
Forfarande for framstellning av 2,5-dihydro-1,2-tiazino/5,6-b/indol-3-karboxamid-1,1-dioxiderInfo
- Publication number
- SE436749B SE436749B SE7714833A SE7714833A SE436749B SE 436749 B SE436749 B SE 436749B SE 7714833 A SE7714833 A SE 7714833A SE 7714833 A SE7714833 A SE 7714833A SE 436749 B SE436749 B SE 436749B
- Authority
- SE
- Sweden
- Prior art keywords
- dihydro
- indole
- thiazino
- dioxide
- hydroxy
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 16
- -1 methoxy, methyl Chemical group 0.000 claims description 84
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
- 150000001875 compounds Chemical class 0.000 claims description 32
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 239000002904 solvent Substances 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 150000007530 organic bases Chemical class 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 150000007529 inorganic bases Chemical class 0.000 claims description 10
- 150000004982 aromatic amines Chemical class 0.000 claims description 9
- 239000000460 chlorine Substances 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
- 239000012948 isocyanate Substances 0.000 claims description 7
- LSGKMZLPZFPAIN-UHFFFAOYSA-N 1h-indole-3-carboxamide Chemical compound C1=CC=C2C(C(=O)N)=CNC2=C1 LSGKMZLPZFPAIN-UHFFFAOYSA-N 0.000 claims description 6
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 150000007513 acids Chemical class 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 5
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 150000001350 alkyl halides Chemical class 0.000 claims description 4
- 238000009835 boiling Methods 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 150000002513 isocyanates Chemical class 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 150000004795 grignard reagents Chemical class 0.000 claims description 3
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 3
- 239000007818 Grignard reagent Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 claims 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- 238000002844 melting Methods 0.000 description 93
- 230000008018 melting Effects 0.000 description 93
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 83
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 43
- 239000011541 reaction mixture Substances 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 34
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 32
- 239000008096 xylene Substances 0.000 description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 239000002244 precipitate Substances 0.000 description 29
- 239000000203 mixture Substances 0.000 description 27
- 238000010992 reflux Methods 0.000 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- 238000001816 cooling Methods 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 22
- 239000007858 starting material Substances 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- XDMOHJCZPMMVOY-UHFFFAOYSA-N methyl 4-hydroxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxylate Chemical compound C1=CC=C2N(C)C(C(O)=C(N(S3(=O)=O)C)C(=O)OC)=C3C2=C1 XDMOHJCZPMMVOY-UHFFFAOYSA-N 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 18
- 239000005457 ice water Substances 0.000 description 17
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 16
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 15
- KMAKOBLIOCQGJP-UHFFFAOYSA-N indole-3carboxylic acid Natural products C1=CC=C2C(C(=O)O)=CNC2=C1 KMAKOBLIOCQGJP-UHFFFAOYSA-N 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 14
- 239000013543 active substance Substances 0.000 description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 14
- 239000000725 suspension Substances 0.000 description 12
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 11
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 10
- KBTUVAIXDZHWAC-UHFFFAOYSA-N 4-hydroxy-2,5-dimethyl-1,1-dioxo-n-(1,3-thiazol-2-yl)thiazino[5,6-b]indole-3-carboxamide Chemical compound OC=1C(N(C2=CC=CC=C22)C)=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=CS1 KBTUVAIXDZHWAC-UHFFFAOYSA-N 0.000 description 10
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 10
- 239000008298 dragée Substances 0.000 description 10
- 239000000499 gel Substances 0.000 description 10
- 239000002585 base Substances 0.000 description 9
- 238000000354 decomposition reaction Methods 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 239000003513 alkali Substances 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- LKGUTMQMKKSSJD-UHFFFAOYSA-N 4-hydroxy-2,5-dimethyl-1,1-dioxo-n-phenylthiazino[5,6-b]indole-3-carboxamide Chemical compound OC=1C(N(C2=CC=CC=C22)C)=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=C1 LKGUTMQMKKSSJD-UHFFFAOYSA-N 0.000 description 7
- 229920002261 Corn starch Polymers 0.000 description 7
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 7
- 230000001476 alcoholic effect Effects 0.000 description 7
- 229910021529 ammonia Inorganic materials 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 235000019359 magnesium stearate Nutrition 0.000 description 7
- 239000002808 molecular sieve Substances 0.000 description 7
- 239000012286 potassium permanganate Substances 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 7
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 6
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 6
- LGQXXHMEBUOXRP-UHFFFAOYSA-N tributyl borate Chemical compound CCCCOB(OCCCC)OCCCC LGQXXHMEBUOXRP-UHFFFAOYSA-N 0.000 description 6
- VTFIKHQLZREHBK-UHFFFAOYSA-N 4-hydroxy-2,5-dimethyl-n-(4-methyl-1,3-thiazol-2-yl)-1,1-dioxothiazino[5,6-b]indole-3-carboxamide Chemical compound OC=1C(N(C2=CC=CC=C22)C)=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC(C)=CS1 VTFIKHQLZREHBK-UHFFFAOYSA-N 0.000 description 5
- OUQMXTJYCAJLGO-UHFFFAOYSA-N 4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(N)=N1 OUQMXTJYCAJLGO-UHFFFAOYSA-N 0.000 description 5
- 102000008186 Collagen Human genes 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
- 230000002776 aggregation Effects 0.000 description 5
- 238000004220 aggregation Methods 0.000 description 5
- 150000001342 alkaline earth metals Chemical class 0.000 description 5
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 239000001632 sodium acetate Substances 0.000 description 5
- 235000017281 sodium acetate Nutrition 0.000 description 5
- MQQYYFQRONHFOF-UHFFFAOYSA-N 1,1-dioxo-3,5-dihydro-2h-thiazino[5,6-b]indol-4-one Chemical compound N1C2=CC=CC=C2C2=C1C(=O)CNS2(=O)=O MQQYYFQRONHFOF-UHFFFAOYSA-N 0.000 description 4
- 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 4
- XMXLBDNVSIHRRA-UHFFFAOYSA-N 4,5-dimethyl-1,3-thiazol-2-amine Chemical compound CC=1N=C(N)SC=1C XMXLBDNVSIHRRA-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 239000005977 Ethylene Substances 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 235000019759 Maize starch Nutrition 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 4
- 150000008046 alkali metal hydrides Chemical class 0.000 description 4
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 4
- DSJNAGSYDWXCNU-UHFFFAOYSA-N ethyl 1,5-dimethylindole-2-carboxylate Chemical compound CC1=CC=C2N(C)C(C(=O)OCC)=CC2=C1 DSJNAGSYDWXCNU-UHFFFAOYSA-N 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- RCPIIXXBICPHNG-UHFFFAOYSA-N methyl 8-chloro-4-hydroxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxylate Chemical compound ClC1=CC=C2N(C)C(C(O)=C(N(S3(=O)=O)C)C(=O)OC)=C3C2=C1 RCPIIXXBICPHNG-UHFFFAOYSA-N 0.000 description 4
- 239000004533 oil dispersion Substances 0.000 description 4
- 230000020477 pH reduction Effects 0.000 description 4
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- 229910000104 sodium hydride Inorganic materials 0.000 description 4
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- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- LBCSENOGVJSBQT-UHFFFAOYSA-N 1-(4-hydroxy-5-methyl-1,1-dioxo-2h-thiazino[5,6-b]indol-3-yl)ethanone Chemical compound C1=CC=C2N(C)C(C(O)=C(NS3(=O)=O)C(=O)C)=C3C2=C1 LBCSENOGVJSBQT-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- CAVBKOSWWBBPAS-UHFFFAOYSA-N 2,5-dimethyl-1,1-dioxo-4-pyrrolidin-1-ylthiazino[5,6-b]indole-3-carbonyl chloride Chemical compound C12=CC=CC=C2N(C)C2=C1S(=O)(=O)N(C)C(C(Cl)=O)=C2N1CCCC1 CAVBKOSWWBBPAS-UHFFFAOYSA-N 0.000 description 3
- MRYKMFIKJPEAHW-UHFFFAOYSA-N 4-hydroxy-2,5-dihydrothiazino[5,6-b]indole-3-carboxylic acid Chemical compound OC1=C(NSC2=C1NC=1C=CC=CC2=1)C(=O)O MRYKMFIKJPEAHW-UHFFFAOYSA-N 0.000 description 3
- VHYUYDBORRZQLE-UHFFFAOYSA-N 4-hydroxy-2,5-dimethyl-1,1-dioxo-n-pyridin-2-ylthiazino[5,6-b]indole-3-carboxamide Chemical compound OC=1C(N(C2=CC=CC=C22)C)=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 VHYUYDBORRZQLE-UHFFFAOYSA-N 0.000 description 3
- LELAZQCIMCCKNQ-UHFFFAOYSA-N 4-hydroxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxamide Chemical compound C1=CC=C2N(C)C(C(O)=C(C(N)=O)N(S3(=O)=O)C)=C3C2=C1 LELAZQCIMCCKNQ-UHFFFAOYSA-N 0.000 description 3
- WELWAYLSDVZBLT-UHFFFAOYSA-N 4-hydroxy-2,5-dimethyl-n-(6-methylpyridin-2-yl)-1,1-dioxothiazino[5,6-b]indole-3-carboxamide Chemical compound OC=1C(N(C2=CC=CC=C22)C)=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC(C)=N1 WELWAYLSDVZBLT-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229910002012 Aerosil® Inorganic materials 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 3
- 230000007059 acute toxicity Effects 0.000 description 3
- 231100000403 acute toxicity Toxicity 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
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- HARKVOVSQJMAGK-UHFFFAOYSA-N methyl 2-(7-chloro-4-methyl-1,1,3-trioxo-[1,2]thiazolo[4,5-b]indol-2-yl)acetate Chemical compound ClC1=CC=C2N(C)C(C(=O)N(S3(=O)=O)CC(=O)OC)=C3C2=C1 HARKVOVSQJMAGK-UHFFFAOYSA-N 0.000 description 1
- KBTFJAKSXBRFCF-UHFFFAOYSA-N methyl 2-ethyl-4-hydroxy-5-methyl-1,1-dioxothiazino[5,6-b]indole-3-carboxylate Chemical compound C1=CC=C2N(C)C(C(O)=C(C(=O)OC)N(S3(=O)=O)CC)=C3C2=C1 KBTFJAKSXBRFCF-UHFFFAOYSA-N 0.000 description 1
- YKCYUMLHFFVUAO-UHFFFAOYSA-N methyl 3-chlorosulfinyl-5-methoxy-1-methylindole-2-carboxylate Chemical compound COC1=CC=C2N(C)C(C(=O)OC)=C(S(Cl)=O)C2=C1 YKCYUMLHFFVUAO-UHFFFAOYSA-N 0.000 description 1
- JBGKLXUHWGUPQT-UHFFFAOYSA-N methyl 3-methoxy-1h-indole-2-carboxylate Chemical compound C1=CC=C2C(OC)=C(C(=O)OC)NC2=C1 JBGKLXUHWGUPQT-UHFFFAOYSA-N 0.000 description 1
- HRFHVPPDEPHJFS-UHFFFAOYSA-N methyl 5-ethyl-4-hydroxy-1,1-dioxo-2h-thiazino[5,6-b]indole-3-carboxylate Chemical compound C1=CC=C2N(CC)C(C(=C(C(=O)OC)NS3(=O)=O)O)=C3C2=C1 HRFHVPPDEPHJFS-UHFFFAOYSA-N 0.000 description 1
- QUZGGDBUGGJROM-UHFFFAOYSA-N methyl 5-fluoro-1h-indole-2-carboxylate Chemical compound FC1=CC=C2NC(C(=O)OC)=CC2=C1 QUZGGDBUGGJROM-UHFFFAOYSA-N 0.000 description 1
- ICLJNGFXULYAIK-UHFFFAOYSA-N methyl 5-methoxy-1-methyl-3-sulfamoylindole-2-carboxylate Chemical compound COC1=CC=C2N(C)C(C(=O)OC)=C(S(N)(=O)=O)C2=C1 ICLJNGFXULYAIK-UHFFFAOYSA-N 0.000 description 1
- ATBRZWKEUADOQF-UHFFFAOYSA-N methyl 5-methoxy-1-methylindole-2-carboxylate Chemical compound COC1=CC=C2N(C)C(C(=O)OC)=CC2=C1 ATBRZWKEUADOQF-UHFFFAOYSA-N 0.000 description 1
- WRGGPMDTZGLUCE-UHFFFAOYSA-N methyl 7-chloro-4-hydroxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxylate Chemical compound C1=C(Cl)C=C2N(C)C(C(O)=C(N(S3(=O)=O)C)C(=O)OC)=C3C2=C1 WRGGPMDTZGLUCE-UHFFFAOYSA-N 0.000 description 1
- NMDDIFPEKRSJSQ-UHFFFAOYSA-N methyl 7-chloro-4-methyl-1,1,3-trioxo-[1,2]thiazolo[4,5-b]indole-2-carboxylate Chemical compound ClC1=CC=C2N(C)C(C(=O)N(S3(=O)=O)C(=O)OC)=C3C2=C1 NMDDIFPEKRSJSQ-UHFFFAOYSA-N 0.000 description 1
- FIHBTCWFINUSEC-UHFFFAOYSA-N methyl 8-bromo-4-hydroxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxylate Chemical compound BrC1=CC=C2N(C)C(C(O)=C(N(S3(=O)=O)C)C(=O)OC)=C3C2=C1 FIHBTCWFINUSEC-UHFFFAOYSA-N 0.000 description 1
- CDYPWKZFCMAOTM-UHFFFAOYSA-N methyl 8-ethyl-4-hydroxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxylate Chemical compound O=S1(=O)N(C)C(C(=O)OC)=C(O)C2=C1C1=CC(CC)=CC=C1N2C CDYPWKZFCMAOTM-UHFFFAOYSA-N 0.000 description 1
- DWUOIVBLJDTMCF-UHFFFAOYSA-N methyl 8-fluoro-4-hydroxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxylate Chemical compound FC1=CC=C2N(C)C(C(O)=C(N(S3(=O)=O)C)C(=O)OC)=C3C2=C1 DWUOIVBLJDTMCF-UHFFFAOYSA-N 0.000 description 1
- IVROOVFVCOJYLD-UHFFFAOYSA-N methyl 9-chloro-4-hydroxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxylate Chemical compound ClC=1C=2C3=C(N(C=2C=CC=1)C)C(=C(N(S3(=O)=O)C)C(=O)OC)O IVROOVFVCOJYLD-UHFFFAOYSA-N 0.000 description 1
- YLGXILFCIXHCMC-JHGZEJCSSA-N methyl cellulose Chemical compound COC1C(OC)C(OC)C(COC)O[C@H]1O[C@H]1C(OC)C(OC)C(OC)OC1COC YLGXILFCIXHCMC-JHGZEJCSSA-N 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- OXMKQXHJBZVQCC-UHFFFAOYSA-N n-(1,3-benzothiazol-2-yl)-4-hydroxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxamide Chemical compound C1=CC=C2N(C)C(C(O)=C(C(=O)NC=3SC4=CC=CC=C4N=3)N(S3(=O)=O)C)=C3C2=C1 OXMKQXHJBZVQCC-UHFFFAOYSA-N 0.000 description 1
- MISGEFQTNFHTAR-UHFFFAOYSA-N n-(3-chlorophenyl)-4-hydroxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxamide Chemical compound OC=1C(N(C2=CC=CC=C22)C)=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC(Cl)=C1 MISGEFQTNFHTAR-UHFFFAOYSA-N 0.000 description 1
- NDDUVSGHTOJLNS-UHFFFAOYSA-N n-(4,5-dimethyl-1,3-thiazol-2-yl)-4-hydroxy-5-methyl-1,1-dioxo-2h-thiazino[5,6-b]indole-3-carboxamide Chemical compound S1C(C)=C(C)N=C1NC(=O)C(NS1(=O)=O)=C(O)C2=C1C1=CC=CC=C1N2C NDDUVSGHTOJLNS-UHFFFAOYSA-N 0.000 description 1
- YQHQWWPBBHTOOP-UHFFFAOYSA-N n-(4-bromophenyl)-4-hydroxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxamide Chemical compound OC=1C(N(C2=CC=CC=C22)C)=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=C(Br)C=C1 YQHQWWPBBHTOOP-UHFFFAOYSA-N 0.000 description 1
- HBJSHNMBGXTJSK-UHFFFAOYSA-N n-(4-ethyl-5-methyl-1,3-thiazol-2-yl)-4-hydroxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxamide Chemical compound S1C(C)=C(CC)N=C1NC(=O)C(N(S1(=O)=O)C)=C(O)C2=C1C1=CC=CC=C1N2C HBJSHNMBGXTJSK-UHFFFAOYSA-N 0.000 description 1
- ZAKFSHITXUNCKU-UHFFFAOYSA-N n-(4-fluorophenyl)-4-hydroxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxamide Chemical compound OC=1C(N(C2=CC=CC=C22)C)=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=C(F)C=C1 ZAKFSHITXUNCKU-UHFFFAOYSA-N 0.000 description 1
- VSJDEJBSOASBGM-UHFFFAOYSA-N n-(5-ethyl-4-methyl-1,3-thiazol-2-yl)-4-hydroxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxamide Chemical compound CC1=C(CC)SC(NC(=O)C=2N(S(=O)(=O)C3=C(N(C4=CC=CC=C43)C)C=2O)C)=N1 VSJDEJBSOASBGM-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- HNHVTXYLRVGMHD-UHFFFAOYSA-N n-butyl isocyanate Chemical compound CCCCN=C=O HNHVTXYLRVGMHD-UHFFFAOYSA-N 0.000 description 1
- MRRXGLCKSKEZEV-UHFFFAOYSA-N n-butyl-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxamide Chemical compound C1=CC=C2N(C)C(C=C(N(S3(=O)=O)C)C(=O)NCCCC)=C3C2=C1 MRRXGLCKSKEZEV-UHFFFAOYSA-N 0.000 description 1
- ZGCZXEKWEVQOHG-UHFFFAOYSA-N n-butyl-4-hydroxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxamide Chemical compound C1=CC=C2N(C)C(C(O)=C(N(S3(=O)=O)C)C(=O)NCCCC)=C3C2=C1 ZGCZXEKWEVQOHG-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical compound COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 description 1
- CQUNNKKPBDGDIE-UHFFFAOYSA-N phenyl 4-hydroxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxylate Chemical compound OC=1C(N(C2=CC=CC=C22)C)=C2S(=O)(=O)N(C)C=1C(=O)OC1=CC=CC=C1 CQUNNKKPBDGDIE-UHFFFAOYSA-N 0.000 description 1
- 210000004623 platelet-rich plasma Anatomy 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical class [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 description 1
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 1
- 238000012958 reprocessing Methods 0.000 description 1
- 150000005619 secondary aliphatic amines Chemical class 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 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
- HSFQBFMEWSTNOW-UHFFFAOYSA-N sodium;carbanide Chemical group [CH3-].[Na+] HSFQBFMEWSTNOW-UHFFFAOYSA-N 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/14—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19772704485 DE2704485A1 (de) | 1977-02-03 | 1977-02-03 | Neue 2,5-dihydro-1,2-thiazino eckige klammer auf 5,6-b eckige klammer zu indol-3-carboxamid-1,1-dioxide, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SE7714833L SE7714833L (sv) | 1978-08-04 |
| SE436749B true SE436749B (sv) | 1985-01-21 |
Family
ID=6000267
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE7714833A SE436749B (sv) | 1977-02-03 | 1977-12-28 | Forfarande for framstellning av 2,5-dihydro-1,2-tiazino/5,6-b/indol-3-karboxamid-1,1-dioxider |
Country Status (35)
| Country | Link |
|---|---|
| US (1) | US4137313A (en]) |
| JP (1) | JPS5398998A (en]) |
| AT (3) | AT355585B (en]) |
| AU (1) | AU516178B2 (en]) |
| BE (1) | BE863588A (en]) |
| BG (1) | BG36499A3 (en]) |
| CA (1) | CA1088064A (en]) |
| CH (1) | CH639389A5 (en]) |
| CS (1) | CS194195B2 (en]) |
| DD (1) | DD134767A5 (en]) |
| DE (1) | DE2704485A1 (en]) |
| DK (1) | DK150517C (en]) |
| ES (5) | ES466555A1 (en]) |
| FI (1) | FI62097C (en]) |
| FR (1) | FR2379542A1 (en]) |
| GB (1) | GB1569238A (en]) |
| GR (1) | GR64418B (en]) |
| HK (1) | HK71383A (en]) |
| HU (1) | HU175550B (en]) |
| IE (1) | IE46185B1 (en]) |
| IL (1) | IL53948A (en]) |
| IT (1) | IT1105151B (en]) |
| LU (1) | LU78974A1 (en]) |
| MY (1) | MY8400283A (en]) |
| NL (1) | NL7801183A (en]) |
| NO (1) | NO148490C (en]) |
| NZ (1) | NZ186374A (en]) |
| PH (1) | PH13882A (en]) |
| PL (1) | PL109705B1 (en]) |
| PT (1) | PT67607B (en]) |
| SE (1) | SE436749B (en]) |
| SG (1) | SG48083G (en]) |
| SU (1) | SU654173A3 (en]) |
| YU (1) | YU24478A (en]) |
| ZA (1) | ZA78630B (en]) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2838377A1 (de) * | 1978-09-02 | 1980-03-20 | Thomae Gmbh Dr K | Neue 4-hydroxy-2h eckige klammer auf 1 eckige klammer zu benzothieno eckige klammer auf 2,3-e eckige klammer zu -1,2- thiazin-3-carboxamid-1,1-dioxide sowie deren salze, deren verwendung und verfahren zu ihrer herstellung |
| AU5811280A (en) | 1979-06-13 | 1980-12-18 | F. Hoffmann-La Roche Ag | Thiazine derivatives |
| GR80576B (en) * | 1983-10-17 | 1984-11-29 | Fujisawa Pharmaceutical Co | Thiazine derivatives, process for preparation thereof and pharmaceutical composition comprising the same |
| US4683306A (en) * | 1984-07-13 | 1987-07-28 | Yuhan Corporation Co., Ltd. | Process for the preparation of 3,4-dihydro-2-substituted-2H-1,2-thiazine-carboxylic acid 1,1-dioxide derivatives |
| US6407124B1 (en) | 1998-06-18 | 2002-06-18 | Bristol-Myers Squibb Company | Carbon substituted aminothiazole inhibitors of cyclin dependent kinases |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH588693A5 (en]) * | 1973-12-10 | 1977-06-15 | Image Analysing Computers Ltd | |
| IL47877A (en) * | 1974-08-26 | 1978-10-31 | Sparamedica Ag | Thienothiazine carboxamide derivatives,their manufacture and pharmaceutical compositions containing them |
| AT345847B (de) * | 1974-11-08 | 1978-10-10 | Thomae Gmbh Dr K | Verfahren zur herstellung neuer 4-hydroxy-2h- naphtho- (2,1-e)-1,2-thiazin-3-carboxamid-1,1-dioxid und deren salze |
-
1977
- 1977-02-03 DE DE19772704485 patent/DE2704485A1/de not_active Withdrawn
- 1977-12-28 SE SE7714833A patent/SE436749B/sv not_active IP Right Cessation
-
1978
- 1978-01-09 AT AT11178A patent/AT355585B/de active
- 1978-01-17 BG BG038411A patent/BG36499A3/xx unknown
- 1978-01-27 IT IT47828/78A patent/IT1105151B/it active
- 1978-01-27 US US05/872,889 patent/US4137313A/en not_active Expired - Lifetime
- 1978-01-30 SU SU782571747A patent/SU654173A3/ru active
- 1978-01-31 CS CS78650A patent/CS194195B2/cs unknown
- 1978-02-01 IL IL53948A patent/IL53948A/xx unknown
- 1978-02-01 HU HU78TO1069A patent/HU175550B/hu unknown
- 1978-02-01 FI FI780324A patent/FI62097C/fi not_active IP Right Cessation
- 1978-02-01 LU LU78974A patent/LU78974A1/de unknown
- 1978-02-01 GR GR55322A patent/GR64418B/el unknown
- 1978-02-01 PH PH20738A patent/PH13882A/en unknown
- 1978-02-01 DD DD78203510A patent/DD134767A5/xx unknown
- 1978-02-02 NL NL7801183A patent/NL7801183A/xx not_active Application Discontinuation
- 1978-02-02 ES ES466555A patent/ES466555A1/es not_active Expired
- 1978-02-02 GB GB4304/78A patent/GB1569238A/en not_active Expired
- 1978-02-02 DK DK048478A patent/DK150517C/da not_active IP Right Cessation
- 1978-02-02 NO NO780370A patent/NO148490C/no unknown
- 1978-02-02 NZ NZ186374A patent/NZ186374A/xx unknown
- 1978-02-02 YU YU00244/78A patent/YU24478A/xx unknown
- 1978-02-02 BE BE184854A patent/BE863588A/xx not_active IP Right Cessation
- 1978-02-02 AU AU32931/78A patent/AU516178B2/en not_active Expired
- 1978-02-02 PL PL1978204401A patent/PL109705B1/pl unknown
- 1978-02-02 ZA ZA00780630A patent/ZA78630B/xx unknown
- 1978-02-02 JP JP1104478A patent/JPS5398998A/ja active Granted
- 1978-02-02 CA CA296,063A patent/CA1088064A/en not_active Expired
- 1978-02-02 CH CH114778A patent/CH639389A5/de not_active IP Right Cessation
- 1978-02-02 PT PT67607A patent/PT67607B/pt unknown
- 1978-02-03 IE IE246/78A patent/IE46185B1/en unknown
- 1978-02-03 FR FR7803158A patent/FR2379542A1/fr active Granted
- 1978-04-25 ES ES469113A patent/ES469113A1/es not_active Expired
- 1978-04-25 ES ES469111A patent/ES469111A1/es not_active Expired
- 1978-04-25 ES ES469112A patent/ES469112A1/es not_active Expired
- 1978-04-25 ES ES469110A patent/ES469110A1/es not_active Expired
-
1979
- 1979-04-11 AT AT269679A patent/AT355591B/de not_active IP Right Cessation
- 1979-04-11 AT AT269579A patent/AT355590B/de not_active IP Right Cessation
-
1983
- 1983-08-10 SG SG48083A patent/SG48083G/en unknown
- 1983-12-20 HK HK713/83A patent/HK71383A/xx unknown
-
1984
- 1984-12-30 MY MY283/84A patent/MY8400283A/xx unknown
Also Published As
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