Fragment-Based Discovery of Pyrimido[1,2-b]indazole PDE10A Inhibitors.
Chem Pharm Bull (Tokyo)
; 66(3): 286-294, 2018.
Article
em En
| MEDLINE
| ID: mdl-29491261
ABSTRACT
In this study, we report the identification of potent pyrimidoindazoles as phosphodiesterase10A (PDE10A) inhibitors by using the method of fragment-based drug discovery (FBDD). The pyrazolopyridine derivative 2 was found to be a fragment hit compound which could occupy a part of the binding site of PDE10A enzyme by using the method of the X-ray co-crystal structure analysis. On the basis of the crystal structure of compound 2 and PDE10A protein, a number of compounds were synthesized and evaluated, by means of structure-activity relationship (SAR) studies, which culminated in the discovery of a novel pyrimidoindazole derivative 13 having good physicochemical properties.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Fosfodiesterase
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Diester Fosfórico Hidrolases
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Indazóis
Limite:
Animals
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Humans
Idioma:
En
Revista:
Chem Pharm Bull (Tokyo)
Ano de publicação:
2018
Tipo de documento:
Article