设计和合成 1,2,4-三唑并[1,5-a]嘧啶衍生物作为 PDE4B 抑制剂，具有支气管扩张活性。
Design and synthesis of 1,2,4-triazolo[1,5-a]pyrimidine derivatives as PDE 4B inhibitors endowed with bronchodilator activity.
机构信息
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Nahda University, Beni Suef, Egypt.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
出版信息
Arch Pharm (Weinheim). 2019 Aug;352(8):e1900002. doi: 10.1002/ardp.201900002. Epub 2019 Jul 29.
A series of 1,2,4-triazolo[1,5-a]pyrimidine derivatives was designed, synthesized, and screened for their phosphodiesterase (PDE 4B) inhibitory activity and bronchodilation ability. Compound 7e showed 41.80% PDE 4B inhibition at 10 µM. Eight compounds were screened for their bronchodilator activity, where compounds 7f and 7e elicited promising bronchodilator activity with EC values of 18.6 and 57.1 µM, respectively, compared to theophylline (EC = 425 µM). Molecular docking at the PDE 4B active site revealed a binding mode and docking scores comparable to those of a reference ligand, consistent with their PDE 4B inhibition activity.
设计、合成并筛选了一系列 1,2,4-三唑并[1,5-a]嘧啶衍生物，以评估它们对磷酸二酯酶 4B（PDE 4B）的抑制活性和支气管扩张能力。化合物 7e 在 10 μM 时对 PDE 4B 的抑制率为 41.80%。对 8 种化合物进行了支气管扩张活性筛选，化合物 7f 和 7e 的 EC 值分别为 18.6 和 57.1 μM，与茶碱（EC = 425 μM）相比具有有前景的支气管扩张活性。在 PDE 4B 的活性部位进行分子对接，揭示了一种与参考配体相当的结合模式和对接评分，与它们的 PDE 4B 抑制活性一致。
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