一些新型哒嗪衍生物的合成、血管舒张活性及二维定量构效关系研究
Synthesis, vasorelaxant activity and 2D-QSAR study of some novel pyridazine derivatives.
作者信息
George Riham F, Saleh Dalia O
机构信息
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, ElKasr El-Aini Street, 11562 Cairo, Egypt.
Pharmacology Department, National Research Centre, Dokki, Giza 12622, Egypt.
出版信息
Eur J Med Chem. 2016 Jan 27;108:663-673. doi: 10.1016/j.ejmech.2015.12.015. Epub 2015 Dec 12.
Novel 3,6-disubstituted pyridazines were synthesized by facile method and screened for their vasorelaxant properties utilizing isolated thoracic rat aortic rings. Compounds 8a and 11a exerted potent vasorelaxant activity (IC50 = 198 and 177 μM, respectively) relative to doxazosin mesylate (used reference standard, IC50 = 226 μM), 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(2)cvOO = 0.7153, R(2)cvMO = 0.7209, F = 17.9708, s(2) = 9.65226 × 10(-8)) that was obtained employing CODESSA-Pro software.
通过简便方法合成了新型3,6-二取代哒嗪，并利用离体大鼠胸主动脉环筛选其血管舒张特性。相对于甲磺酸多沙唑嗪（用作参考标准，IC50 = 226 μM），化合物8a和11a表现出较强的血管舒张活性（IC50分别为198和177 μM），它们可能是治疗心血管疾病的有前景的候选物。通过使用CODESSA-Pro软件获得的具有统计学意义的QSAR模型（N = 32，n = 6，R(2) = 0.811782，R(2)cvOO = 0.7153，R(2)cvMO = 0.7209，F = 17.9708，s(2) = 9.65226 × 10(-8)）验证了观察到的活性。
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