Synthesis, vasorelaxant activity and 2D-QSAR study of some novel pyridazine derivatives

被引：21
作者：
George, Riham F. [1 ]
Saleh, Dalia O. [2 ]
机构：
[1] Cairo Univ, Dept Pharmaceut Chem, Fac Pharm, ElKasr El Aini St, Cairo 11562, Egypt
[2] Natl Res Ctr, Dept Pharmacol, Giza 12622, Egypt
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 108卷
关键词：
Pyridazines; Vasodilator; QSAR; ANGIOTENSIN RECEPTOR BLOCKERS; CONVERTING ENZYME-INHIBITORS; PHOSPHODIESTERASE INHIBITORS; REGIOSELECTIVE SYNTHESIS; CARDIOTONIC AGENTS; RATIONAL DESIGN; HEART-DISEASE; QSAR; DRUG; BIOASSAY;
D O I：
10.1016/j.ejmech.2015.12.015
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Novel 3,6-disubstituted pyridazines were synthesized by facile method and screened for their vaso-relaxant properties utilizing isolated thoracic rat aortic rings. Compounds 8a and Ha exerted potent vasorelaxant activity (IC50 = 198 and 177 mu M, respectively) relative to doxazosin mesylate (used reference standard, IC50 = 226 mu M), that, they may represent promising hits for treatment of cardiovascular disorders. The observed activity was validated by a statistically significant QSAR model (N = 32, n = 6, R-2 = 0.811782, R-cvOO(2) = 0.7153, R-cvMO(2) = 0.7209, F = 17.9708, s(2) = 9.65226 x 10(-8)) that was obtained employing CODESSA-Pro software. (C) 2015 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：663 / 673
页数：11
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