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Cardiotonic agents. 2. Synthesis and structure-activity relationships of 4,5-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones: a new class of positive inotropic agents.
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 1985-10-01 , DOI: 10.1021/jm00148a006
I Sircar , B L Duell , G Bobowski , J A Bristol , D B Evans

A series of 4,5-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones and related compounds were synthesized and evaluated for positive inotropic activity. Most members of this series produced dose-related increases in myocardial contractility that were associated with relatively minor increases in heart rate and decreases in systemic arterial blood pressure. Introduction of a methyl substituent at the 5-position of 1 (CI-914) produced the most potent compound in this series (11, CI-930). Compound 1 is more potent than amrinone whereas compound 11 is more potent than milrinone. The inotropic effects of 1 and 11 are not mediated via stimulation of beta-adrenergic receptors. Selective inhibition of cardiac phosphodiesterase fraction III represents the principal component of the positive inotropic action of 1 and 11.

中文翻译:

强心剂。2. 4,5-二氢-6- [4-(1H-咪唑-1-基)苯基] -3(2H)-哒嗪酮的合成及其构效关系:一类新型的正性变力剂。

合成了一系列的4,5-二氢-6- [4-(1H-咪唑-1-基)苯基] -3(2H)-哒嗪酮和相关化合物,并评价其正性肌力活性。该系列的大多数成员产生剂量相关的心肌收缩力增加,这与心率相对较小的升高和全身动脉血压的降低有关。在1的5位上引入甲基取代基(CI-914)产生了该系列中最有效的化合物(11,CI-930)。化合物1比氨力农更有效,而化合物11比米力农更有效。1和11的正性肌力作用不是通过刺激β-肾上腺素受体介导的。心脏磷酸二酯酶组分III的选择性抑制代表1和11的正性肌力作用的主要成分。
更新日期:2019-11-01
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