| 摘要 |
<p>1373261 8 - Amino - 1,2,4 - pyrimido[4,5-e]- thiadiazine-1,1-dioxides SANDOZ Ltd 17 Jan 1972 [20 Jan 1971] 2088/72 Heading C2C Novel 8 - amino - 1,2,4 - pyrimido[4,5-e]- thiadiazine-1,1-dioxides of the general formula wherein R 1 is a hydrogen atom or a C 1-4 alkyl, phenyl, C 3-6 cycloalkyl, -XNR 3 R 5 or -X-Cl group, in which each of R 3 and R 5 is a hydrogen atom or a C 1-4 alkyl group and X is a C 1-4 alkylene group; R 2 is a hydrogen atom, a -S-R 4 or -SO 2 R 4 group, in which R 4 is a C 1-4 alkyl group, or a -NR 6 R 7 group, in which each of R 6 and R 7 is a hydrogen atom or a C 1-8 alkyl, C 3-5 alkenyl or phenyl group or NR 6 R 7 is a piperazino or morpholino group; and either each of A and B is a hydrogen atom or A and B together signify a second bond between the nitrogen and carbon atoms to which they are respectively attached; provided that when R 2 is a -S-R 4 group, then R 1 is other than a hydrogen atom; that when R 2 is a -S-R 4 group and A and B together form a second bond, then R 1 is other than a methyl group; and that when R 2 is a hydrogen atom and A and B together form a second bond, then R 1 is other than a hydrogen atom; and alkali metal and acid addition salts thereof are prepared (a) when R 2 is a hydrogen atom or a -S-R 4 or -NR 6 R 7 group and each of A and B is a hydrogen atom, by reduction of the corresponding compound in which A and B together form a second bond with a metal hydride in a solvent; (b) when R 1 is other than a -XNR 3 R 5 group and A and B together form a second bond, by reaction of a 4,6-diamino-5- pyrimidinesulphonamide of the general formula with a compound of the general formula wherein R 8 is a methyl, ethyl or n-propyl group; (c) when R 2 is other than a -NR 6 R 7 group, in which each of R 6 and R 7 is a hydrogen atom, R 1 is other than a -XNR 3 R 5 group and A and B together form a second bond, by cyclization (with heating) of a 4-acylamino-6-amino- 5-pyrimidinesulphonamide of the general formula wherein R 2 <SP>11</SP> and R 1 <SP>111</SP> correspond to the desired values of R 2 and R 1 , respectively; (d) when R 2 is a -SO 2 R 4 group, by oxidation of the corresponding compound, which R 2 is a -S-R 4 group in an organic acid solvent; (e) when R 2 is a hydrogen atom and each of A and B is a hydrogen atom, by treatment of the corresponding compound in which R 2 is a -SO 2 R 4 group and A and B together form a second bond with a metal hydride reducing agent in a protolytic solvent; (f) when R 2 is a -NR 6 R 7 group, by reaction of the corresponding compound in which R 2 is a -SO 2 R 4 group with a compound of the general formula R 6 R 7 NH; and (g) when R 1 is a -XNR 3 R 5 group and R 2 is other than a -SO 2 R 4 group, by reaction of the corresponding compound in which R 1 is a -X-Cl group with a compound of the general formula HNR 3 R 5 ; and optional isolation of the product as a salt. 4,6 - Diamino - 5 - pyrimidinesulphonamides of the second general formula above wherein R 2 is a -NR 6 R 7 group are prepared by reaction of the corresponding compound in which R 2 is a -SO 2 R 4 group with a compound of the general formula R 6 R 7 NH. 4 - Acylamino - 6 - amino - - 5 - pyrimidine. sulphonamides of the fourth general formula above are prepared by reaction of a 4,6-diamino- 5-pyrimidinesulphonamide of the second general formula above wherein R 2 is other than a -NR 6 R 7 group, in which each of R 6 and R 7 is a hydrogen atom with a compound of the general formula R 1 COQ, wherein R 1 is other than a -XNR 3 R 5 group and Q is a hydroxy group or a chlorine or bromine atom, in an inert polar solvent. Pharmaceutical compositions having hypotensive/anti-hypertensive activity comprise, as active ingredient, an 8-amino-1,2,4-pyrimido- [4,5-e]thiadiazine - 1,1 - dioxide of the first general formula above or a pharmaceutically acceptable alkali metal or acid addition salt thereof, in association with a pharmaceutically acceptable diluent or carrier, and may be administered orally or parenterally.</p> |
