| 摘要 |
<p>1281361 6 - Amino - 4 - oxo - 4,5 - dihydroisothiazolo[5,4-d]pyrimidines CIBA GEIGY AG 10 Oct 1969 [17 Oct 1968 15 Sept 1969] 49920/69 Heading C2C Novel 6-amino-4-oxo-4,5-dihydroisothiazolo- [5,4-d]pyrimidines of the general formula wherein R 1 is an optionally substituted hydrocarbon residue, R 2 is a hydrogen atom, an optionally substituted hydrocarbon residue, a heterocyclic residue of aromatic character or a heterocyclic-aliphatic residue in which the heterocyclic portion is of aromatic character and Am is a primary, secondary or tertiary amino group, and tautomers and acid-addition salts thereof are prepared by reaction of a 4 - oxo - 4,5 - dihydroisothiazolo[5,4-d]pyrimidine of the general formula wherein X is a reactive esterified hydroxyl group, with an amine of the general formula HAm, followed optionally by salification of the product. 4 - Oxo - 4,5 - dihydroisothiazolo[5,4-d]pyrimidines of the second general formula above wherein X is a halogen atom are prepared by reaction of the corresponding 6-hydroxy-4-oxo-4,5-dihydro-isothiazolo[5,4-d]pyrimidine with a phosphorus halide or oxyhalide and, when a 4,6- dihalo - isothiarolo[5,4 - d] - pyrimidine is formed as an intermediate, treatment thereof with an aqueous alkali metal hydroxide. 6 - Hydroxy - 4 - oxo - 4,5 - dihydro - isothiazolo[5,4-d] - pyrimidines are prepared by reaction of a 3 - R 1 - 4 - ethoxycarbonyl - 5- phenoxycarbonylamino - isothiazole with an amine of the general formula R 2 NH 2 and cyclization of the resulting 3-R 1 -4-ethoxycarbonyl-5- [N - (R 2 - carbamoyl)amino] - isothiazole with sodium in ethanol or aqueous sodium hydroxide. 3 - R 1 - 4 - ethoxycarbonyl - 5 - phenoxycarbonylamino-isothiazoles are prepared by reaction of an amino ester of the general formula with potassium thiocyanate and phenyl chloroformate and cyclization of the resulting carbamic acid of the general formula with bromine in ethyl acetate. Pharmaceutical compositions having central nervous system depressant activity comprise, as active ingredient, a 6-amino-4-oxo-4,5- dihydroisothiazolo[5,4-d]pyrimidine of the first general formula above or a tautomer or physiologically tolerable acid-addition salt thereof, in conjunction or admixture with a pharmaceutical carrier and may be administered enterally or parenterally.</p> |
