Discovery of Dipyridamole Analogues with Enhanced Metabolic Stability for the Treatment of Idiopathic Pulmonary Fibrosis.
Molecules
; 27(11)2022 May 26.
Artigo
em Inglês
| MEDLINE | ID: covidwho-1866459
ABSTRACT
Dipyridamole, apart from its well-known antiplatelet and phosphodiesterase inhibitory activities, is a promising old drug for the treatment of pulmonary fibrosis. However, dipyridamole shows poor pharmacokinetic properties with a half-life (T1/2) of 7 min in rat liver microsomes (RLM). To improve the metabolic stability of dipyridamole, a series of pyrimidopyrimidine derivatives have been designed with the assistance of molecular docking. Among all the twenty-four synthesized compounds, compound (S)-4h showed outstanding metabolic stability (T1/2 = 67 min) in RLM, with an IC50 of 332 nM against PDE5. Furthermore, some interesting structure-activity relationships (SAR) were explained with the assistance of molecular docking.
Palavras-chave
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
MEDLINE
Assunto principal:
Dipiridamol
/
Fibrose Pulmonar Idiopática
Limite:
Animais
Idioma:
Inglês
Assunto da revista:
Biologia
Ano de publicação:
2022
Tipo de documento:
Artigo
País de afiliação:
Molecules27113452
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