Design and synthesis of pyrazolo[3,4-d]pyrimidinone derivatives: Discovery of selective phosphodiesterase-5 inhibitors.
Bioorg Med Chem Lett
; 30(16): 127337, 2020 08 15.
Article
em En
| MEDLINE
| ID: mdl-32631538
ABSTRACT
A novel series of 1,6-disubstituted pyrazolo[3,4-d]pyrimidin-7-one derivatives, 2a-h, 4a-d, 5 and 6, were successfully synthesized, which showed promising, and potent inhibition of phosphodiesterase 5 (PDE5). The inhibitory activities of 5, 4b, 2a, 2d, 2f, 4d and 4a against PDE5 were similar to that of sildenafil (100%). These compounds exhibited potent relaxant effects on isolated rat cavernosum tissue with pEC50 values ranging from 8.31 to 5.16 µM. Pyrazolo[3,4-d]pyrimidin-7-one scaffolds have been rationally designed via consecutive molecular modelling studies prior to their synthesis and biological evaluation. In addition, the results of the pharmacophore-based virtual screening revealed that 1v0p_PVB might have promising activity as a PDE-5 inhibitor.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
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Pirimidinas
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Nucleotídeo Cíclico Fosfodiesterase do Tipo 5
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Descoberta de Drogas
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Inibidores da Fosfodiesterase 5
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Egito