Chemical modification and structure-activity relationships of pyripyropenes. 2. 1,11-Cyclic analogs.
Chemical modification and structure-activity relationships of pyripyropenes. 2. 1,11-Cyclic analogs.
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吡啶罗平的化学修饰和构效关系。
DOI：
10.7164/antibiotics.49.1149
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
S. Ōmura
中科院分区：
文献类型：
--
作者：
R. Obata;T. Sunazuka;Y. Kato;H. Tomoda;Y. Harigaya;S. Ōmura
制备了一系列的1,11环吡咯烯A类似物。用1,11环缩醛取代吡烯的1,11-酰基，有效地提高了体外酰基辅酶a：胆固醇酰基转移酶（ACAT）的抑制活性。尤其值得注意的是苯并二烯缩醛类似物35，它是迄今为止制备的衍生物中最有效的抑制剂（IC50 = 5.6 nM），其抑制活性是pyripyropena的16倍。
A series of 1,11-cyclic analogs of pyripyropene A were prepared. Replacement of the 1,11-acyl groups of pyripyropenes with 1,11-cyclic acetals effectively improved in vitro acyl CoA:cholesterol acyltransferase (ACAT) inhibitory activity. Especially noteworthy is benzylidene acetal analog 35, the most potent inhibitor (IC50 = 5.6 nM) among the derivatives prepared so far, which showed 16 times more potent inhibitory activity than pyripyropene A.