Cyclic HIV protease inhibitors: design and synthesis of orally bioavailable, pyrazole P2/P2' cyclic ureas with improved potency.
J Med Chem
; 41(12): 2019-28, 1998 Jun 04.
Article
em En
| MEDLINE
| ID: mdl-9622543
ABSTRACT
Highly potent HIV-1 protease (HIVPR) inhibitors have been designed and synthesized by introducing bidentate hydrogen-bonding oxime and pyrazole groups at the meta-position of the phenyl ring on the P2/P2' substituents of cyclic ureas. Nonsymmetrical cyclic ureas incorporating 3(1H)-pyrazolylbenzyl as P2 and hydrophilic functionalities as P2' show potent protease inhibition and antiviral activities against HIV and have good oral bioavailabilities. The X-ray structure of HIVPR.10A complex confirms that the two pyrazole rings of 10A form bidentate hydrogen bonds with the side-chain oxygen (C=O) and backbone nitrogen (N-H) of Asp30/30' of HIVPR.
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Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Azepinas
/
Desenho de Fármacos
/
Inibidores da Protease de HIV
/
Fármacos Anti-HIV
Limite:
Animals
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos