Design and synthesis of 1,2,4-triazolo[1,5-a]pyrimidine derivatives as PDE 4B inhibitors endowed with bronchodilator activity

被引：10

作者：

Abd El-Aleam, Rehab H. ^{[1
]}

George, Riham F. ^{[2
]}

Lee, Kevin J. ^{[3
]}

Keeton, Adam B. ^{[3
]}

Piazza, Gary A. ^{[3
]}

Kamel, Amr A. ^{[4
]}

El-Daly, Mahmoud E. ^{[4
]}

Hassan, Ghaneya S. ^{[2
,5
]}

Abdel-Rahman, Hamdy M. ^{[1
,6
]}

机构：

[1] Nanda Univ, Fac Pharm, Pharmaceut Chem Dept, Bani Suwayf, Egypt

[2] Cairo Univ, Fac Pharm, Pharmaceut Chem Dept, Cairo 11562, Egypt

[3] Univ S Alabama, USA Mitchell Canc Inst, Drug Discovery Lab, Mobile, AL USA

[4] Minia Univ, Fac Pharm, Pharmacol & Toxicol Dept, El Minia, Egypt

[5] Badr Univ, Fac Pharm, Pharmaceut Chem Dept, Cairo, Egypt

[6] Assiut Univ, Fac Pharm, Med Chem Dept, Assiut, Egypt

来源：

ARCHIV DER PHARMAZIE | 2019年 / 352卷 / 08期

关键词：

1,2,4-triazolo[1,5-a]pyrimidine; bronchodilator activity; phosphodiesterase; 4B; ASTHMA; POTENT; ACTIVATION;

D O I：

10.1002/ardp.201900002

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

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 mu M. Eight compounds were screened for their bronchodilator activity, where compounds 7f and 7e elicited promising bronchodilator activity with EC50 values of 18.6 and 57.1 mu M, respectively, compared to theophylline (EC50 = 425 mu M). 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.

引用

页数：11

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