Piperazine-based CCR5 antagonists as HIV-1 inhibitors. IV. Discovery of 1-[(4,6-dimethyl-5-pyrimidinyl)carbonyl]- 4-[4-[2-methoxy-1(R)-4-(trifluoromethyl)phenyl]ethyl-3(S)-methyl-1-piperazinyl]- 4-methylpiperidine (Sch-417690/Sch-D), a potent, highly selective, and orally bioavailable CCR5 antagonist.
J Med Chem
; 47(10): 2405-8, 2004 May 06.
Article
em En
| MEDLINE
| ID: mdl-15115380
ABSTRACT
The nature and the size of the benzylic substituent are shown to be the key to controlling receptor selectivity (CCR5 vs M1, M2) and potency in the title compounds. Optimization of the lead benzylic methyl compound 3 led to the methoxymethyl analogue 30, which had excellent receptor selectivity and oral bioavailability in rats and monkeys. Compound 30 (Sch-417690/Sch-D), a potent inhibitor of HIV-1 entry into target cells, is currently in clinical trials.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Piperazinas
/
Piperidinas
/
Pirimidinas
/
HIV-1
/
Fármacos Anti-HIV
/
Canais de Potássio de Abertura Dependente da Tensão da Membrana
/
Antagonistas dos Receptores CCR5
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos