SUBSTITUTED ALKYLPYRIDINES AS P-3' LIGANDS FOR THE HYDROXYETHYLPIPERAZINE CLASS OF HIV-1 PROTEASE INHIBITORS - IMPROVED PHARMACOKINETIC PROFILES

Authors
KIM BM HANIFIN CM ZARTMAN CB VACCA JP MICHELSON SR LIN JH CHEN IW VASTAG K DARKE PL ZUGAY JA EMINI EA SCHLEIF W ANDERSON PS HUFF JR
Citation
Bm. Kim et al., SUBSTITUTED ALKYLPYRIDINES AS P-3' LIGANDS FOR THE HYDROXYETHYLPIPERAZINE CLASS OF HIV-1 PROTEASE INHIBITORS - IMPROVED PHARMACOKINETIC PROFILES, Bioorganic & medicinal chemistry letters, 5(19), 1995, pp. 2239-2244
Citations number
19
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
5
Issue
19
Year of publication
1995
Pages
2239 - 2244
Database
ISI
SICI code
0960-894X(1995)5:19<2239:SAAPLF>2.0.ZU;2-W
Abstract
As a systematic approach to develop HIV-1 protease inhibitors exhibiti ng desirable pharmacokinetic profiles, hydroxyethylpiperazine series o f inhibitors containing various mono- or dialkyl-substituted pyridylme thyl groups have been examined. Very high enzyme inhibitory potency an d antiviral activity in a whole cell assay were observed with these in hibitors and, when administered orally to dogs, selected compounds in this series exhibited prolonged half-lives compared to the non-substit uted pyridylmethyl compound 1.