含硫黄ピリミド[5,4-d]ピリミジン化合物の合成研究(第1報)2位にメチルスルホニル基またはスルホンアミド基を有するピリミド[5,4-d]ピリミジン誘導体の合成

概要

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Thirty-one kinds of pyrimido[5,4-d]pyrimidine derivatives possessing methylsulfonyl or sulfonamide group at 2-position were prepared by the reaction of 4,8-disubstituted 6-chloro-2-methylsulfonylpyrimido[5,4-d]pyrimidine (Va-c) or 4,8-disubstituted 6-chloropyrimido[5.4-d]pyrimidine-2-sulfonyl chloride (IXa-b) and various amines. Reaction of N, N-bis(2-hydroxyethyl)-6-chloro-4,8-dipiperidinopyrimido[5,4-d]pyrimidine-2-sulfonamide (Xa-10) with an excess of diethanolamine by heating to gave dipyridamole (XIIIa) with elimination of the SO_2 group. N-(2-Hydroxyethyl)-N-methyl-sulfonamide derivative (Xa-11) also underwent a similar elimination of the SO_2 group. The relationship between the structure of these derivatives and their activity as coronary vasodilators and inhibitor of platelet aggregation was examined. 6-Bis(2-hydroxyethyl)amino-2-methylsulfonyl-4,8-dipiperidinopyrimido[5,4-d]pyrimidine (VIa) exhibited a strong coronary vasodilation, and sulfonamide derivatives (XIa-10,12,14,and XIIa) exhibited a comparatively strong inhibition of platelet aggregation.
公益社団法人日本薬学会の論文
1976-05-25