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3-[[[3-[2-(7-氯喹啉-2-基)-(E)-乙烯基]苯基][[3-(二甲基氨基)-3-氧代丙基]硫基]甲基]硫基]丙酸对映体的立体定向合成、绝对构型确定及其生物活性,该化合物是一种强效且特异的白三烯D4受体拮抗剂。

Stereospecific synthesis, assignment of absolute configuration, and biological activity of the enantiomers of 3-[[[3-[2-(7-chloroquinolin-2-yl)-(E)-ethenyl]phenyl] [[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]propionic acid, a potent and specific leukotriene D4 receptor antagonist.

作者信息

Gauthier J Y, Jones T, Champion E, Charette L, Dehaven R, Ford-Hutchinson A W, Hoogsteen K, Lord A, Masson P, Piechuta H

机构信息

Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, Quebec, Canada.

出版信息

J Med Chem. 1990 Oct;33(10):2841-5. doi: 10.1021/jm00172a025.

Abstract

The enantiomers of the leukotriene D4 antagonist 3-[[[3-[2-(7-chloroquinolin-2-yl)-(E)-ethenyl]phenyl] [[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]propionic acid (L-660,711)(MK-571) have been prepared, their absolute stereochemistry has been assigned as S for (+)-1 and R for (-)-1 by X-ray analysis of a synthetic intermediate (5), and the biological activity of the enantiomers has been explored. Unexpectedly, the enantiomers are both comparably biologically active with (+)-1 slightly more intrinsically active at the LTD4 receptor in vitro.

摘要

白三烯D4拮抗剂3-[[[3-[2-(7-氯喹啉-2-基)-(E)-乙烯基]苯基][[3-(二甲基氨基)-3-氧代丙基]硫代]甲基]硫代]丙酸(L-660,711)(MK-571)的对映体已被制备出来,通过对一种合成中间体(5)的X射线分析,确定了它们的绝对立体化学构型,即(+)-1为S构型,(-)-1为R构型,并对这些对映体的生物活性进行了研究。出乎意料的是,这两种对映体在生物学活性上相当,其中(+)-1在体外对LTD4受体的内在活性略高。

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