4-(2-氨基乙基)-2(3H)-吲哚酮及相关化合物作为外周节前多巴胺受体激动剂的合成与体外评价

Syntheses and in vitro evaluation of 4-(2-aminoethyl)-2(3H)-indolones and related compounds as peripheral prejunctional dopamine receptor agonists.

作者信息

DeMarinis R M, Gallagher G, Hall R F, Franz R G, Webster C, Huffman W F, Schwartz M S, Kaiser C, Ross S T, Wilson J W

出版信息

J Med Chem. 1986 Jun;29(6):939-47. doi: 10.1021/jm00156a010.

Abstract

A series of (beta-aminoethyl)indolones and related compounds was synthesized and evaluated in vitro as peripheral prejunctional dopaminergic agonists in the field-stimulated isolated perfused rabbit ear artery. 4-[2-(Di-n-propylamino)ethyl]-7-hydroxy-2(3H)-indolone was the most potent compound (ED50 = 2 +/- 0.3 nM) tested, while the related secondary amine 24 and the des-OH derivatives 28 and 34 were only slightly less potent. 4-Methoxybenzeneethanamine and 2-methyl-3-nitrophenylacetic acid were employed as starting materials for for the synthesis of the 4-(beta-aminoethyl)indolones. The ring-opened 3-acylamino analogues 46 and 47 were prepared via nitration of the phenethylamine 43 derived from 4-methoxyphenylacetic acid. The inactive isomeric indolones 38, 39, and 41 were derived from 4-nitrobenzeneethanamine and from indolone-6-acetic acid.

摘要

合成了一系列（β-氨基乙基）吲哚酮及相关化合物，并在体外对其作为外周节前多巴胺能激动剂进行了评估，实验采用场刺激的离体灌流兔耳动脉。4-[2-（二正丙基氨基）乙基]-7-羟基-2（3H）-吲哚酮是所测试的最有效化合物（ED50 = 2±0.3 nM），而相关的仲胺24以及去羟基衍生物28和34的效力仅略低。以4-甲氧基苯乙胺和2-甲基-3-硝基苯乙酸作为起始原料来合成4-（β-氨基乙基）吲哚酮。通过对由4-甲氧基苯乙酸衍生的苯乙胺43进行硝化反应，制备了开环的3-酰基氨基类似物46和47。无活性的异构体吲哚酮38、39和41由4-硝基苯乙胺和吲哚酮-6-乙酸衍生而来。