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Design and synthesis of 1,2,4‐triazolo[1,5‐ a ]pyrimidine derivatives as PDE 4B inhibitors endowed with bronchodilator activity
Author(s) -
Abd ElAleam Rehab H.,
George Riham F.,
Lee Kevin J.,
Keeton Adam B.,
Piazza Gary A.,
Kamel Amr A.,
ElDaly Mahmoud E.,
Hassan Ghaneya S.,
AbdelRahman Hamdy M.
Publication year - 2019
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201900002
Subject(s) - bronchodilator , pyrimidine , theophylline , chemistry , bronchodilation , docking (animal) , stereochemistry , bronchodilator agents , phosphodiesterase , pharmacology , pyrimidine metabolism , enzyme , biochemistry , medicine , purine , asthma , nursing
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 50 values of 18.6 and 57.1 µM, respectively, compared to theophylline (EC 50 = 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.