5,6-外向-环氧-7-氧杂双环[2.2.1]庚烷衍生物的合成与药理评价
Synthesis and pharmacological evaluation of 5,6-exo-epoxy-7-oxabicyclo[2.2.1]heptane derivatives.
作者信息
Das J, Vu T, Harris D N, Ogletree M L
机构信息
Department of Chemistry, Squibb Institute for Medical Research, Princeton, New Jersey 08543-4000.
出版信息
J Med Chem. 1988 May;31(5):930-5. doi: 10.1021/jm00400a007.
1 alpha,2 beta(5Z),3 beta(1E,3S),4 alpha,5 alpha,6 alpha]-7-[5,6-Epoxy-3- (3-cyclohexyl-3-hydroxy-3-methyl-1-propenyl)-7-oxabicyclo[2.2.1]-hept-2- yl]-5-heptenoic acid (31) and [1 alpha,2 beta(5Z),3 beta(1E,3S),4 alpha,5 alpha,6 alpha]-7-[5,6-epoxy-3-[3-hydroxy-5-(p-hydroxyphenyl)-1- pentenyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (37) were found to be selective TxA2 antagonists at the platelet and pulmonary thromboxane receptors. An efficient stereospecific synthesis of these compounds and a series of structural analogues is described. Compounds 31 and 37 both inhibited the bronchoconstriction induced by arachidonic acid in the anesthetized guinea pig.
[1α,2β(5Z),3β(1E,3S),4α,5α,6α]-7-[5,6-环氧-3-(3-环己基-3-羟基-3-甲基-1-丙烯基)-7-氧杂双环[2.2.1]庚-2-基]-5-庚烯酸(31)和[1α,2β(5Z),3β(1E,3S),4α,5α,6α]-7-[5,6-环氧-3-[3-羟基-5-(对羟基苯基)-1-戊烯基]-7-氧杂双环[2.2.1]庚-2-基]-5-庚烯酸(37)被发现是血小板和肺血栓素受体上的选择性血栓素A2拮抗剂。本文描述了这些化合物及一系列结构类似物的有效立体定向合成方法。化合物31和37均能抑制麻醉豚鼠中由花生四烯酸诱导的支气管收缩。
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