1-取代-2-烷基-4-氯-1,6-二氢-6-甲基-5-嘧啶甲酸乙酯类化合物的合成及其降压活性

Synthesis and Antihypertensive Activity of Ethyl-1-Substituted-2-Alkyl-4-Chloro-1,6-Dihydro-6-Methyl-5-Pyrimidinecarboxylates

为寻找新的高效的非肽类血管紧张素 ( A )受体拮抗剂 ,以 losartan为先导 ,根据其 SAR,结合计算机辅助分子结构模拟研究结果 ,设计并合成了 8个 1-取代 - 2 -烷基 - 4-氯 - 1,6-二氢 - 6-甲基 - 5-嘧啶甲酸乙酯类衍生物。所有目标化合物均未见文献报道 ,其结构经 IR、1HNMR和 MS鉴定。初步药理研究表明 ,化合物

Nonpeptide Angiotensin Ⅱ receptor antagonist losartan(Ⅰ) is orally bio available and possesses good antihypertensive activity with a long duration of action. In order to search for the new drug with high potency, derived from the lead compound losartan, and based on the principle of bioisoterism and the result of computer assisted molecular modeling study, eight derivatives of ethyl 1 substituted 2 alkyl 4 chloro 1,6 dihydro 6 methyl 5 pyrimidinecarboxylates were designed and synthesized. Their structures were confirmed by IR\, \+1HNMR and MS spectroscopic elucidation. In preliminary biological tests, compound Ⅱh showed an antihypertensive activity.