INDOLINE ANALOGS OF IDAZOXAN - POTENT ALPHA-2-ANTAGONISTS AND ALPHA-1-AGONISTS
INDOLINE ANALOGS OF IDAZOXAN - POTENT ALPHA-2-ANTAGONISTS AND ALPHA-1-AGONISTS
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DOI：
10.1021/jm00400a009
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发表时间：
1988-05-01
影响因子：
7.3
通讯作者：
WELBOURN, AP
中科院分区：
文献类型：
--
作者：
FAGAN, GP;CHAPLEO, CB;WELBOURN, AP
合成和α-描述了一系列取代的2-咪唑啉基吲哚啉的肾上腺素能活性。在吲哚啉环中的取代产生具有肾上腺素受体拮抗剂/激动剂谱的化合物，该谱被证明对取代基的性质和位置都敏感。许多衍生物具有比相应的苯并二氧杂环己烷1、二氢苯并呋喃2和茚满3类似物更大的突触前拮抗剂效力;然而，这种α 2-拮抗作用通常伴随着α 1-激动剂活性。在该系列中不可能将α 2-拮抗剂与α 1-激动剂特性分开。最感兴趣的化合物证明是N-乙基6，5-氯-N-甲基18和5-氯-N-乙基23衍生物，它们都是有效的α 2-拮抗剂和α 1-激动剂。在吲哚啉环的4-和7-位的取代通常得到具有非选择性激动剂性质的化合物。
The synthesis and .alpha.-adrenergic activity of a series of substituted 2-imidazolinylindolines are described. Substitution in the indoline ring generated compounds with a spectrum of adrenoceptor antaogonist/agonist profiles that proved sensitive to both the nature and position of the substituent. Many of the derivatives possess greater presynaptic antagonist potency than the corresponding benzodioxan 1, dihydrobenzofuran 2, and indan 3 analogues; however, this .alpha.2-antagonism is often accompanied by .alpha.1-agonist activity. It was not possible to separate .alpha.2-antagonist from .alpha.1-agonist properties in this series. Compounds of most interest proved to be the N-ethyl 6,5-chloro-N-methyl 18, and 5-chloro-N-ethyl 23 derivatives, all being potent .alpha.2-antagonists and .alpha.1-agonists. Substitution at the 4- and 7-position of the indoline ring generally gave compounds with nonselective agonist properties.