Piperazine-based CCR5 antagonists as HIV-1 inhibitors. II. Discovery of 1-[(2,4-dimethyl-3-pyridinyl)carbonyl]-4- methyl-4-[3(S)-methyl-4-[1(S)-[4-(trifluoromethyl)phenyl]ethyl]-1-piperazinyl]- piperidine N1-oxide (Sch-350634), an orally bioavailable, potent CCR5 antagonist

Autor:	J R, Tagat, R W, Steensma, S W, McCombie, D V, Nazareno, S I, Lin, B R, Neustadt, K, Cox, S, Xu, L, Wojcik, M G, Murray, N, Vantuno, B M, Baroudy, J M, Strizki
Rok vydání:	2001
Předmět:	Anti-HIV Agents Administration Oral Biological Availability In Vitro Techniques Piperazines Cell Line Rats Cyclic N-Oxides Macaca fascicularis Structure-Activity Relationship Dogs CCR5 Receptor Antagonists HIV-1 Leukocytes Mononuclear Animals
Zdroj:	Journal of medicinal chemistry. 44(21)
ISSN:	0022-2623
Popis:	Truncation of the original piperidino-2(S)-methyl piperazine lead structure 2, from a family of muscarinic antagonists, gave compound 8 which has improved selectivity for the HIV-1 co-receptor CCR5 over muscarinic receptors. Further optimization for pharmacokinetic properties afforded Sch-350634 (1), a prototypical piperazine-based CCR5 antagonist, which is a potent inhibitor of HIV-1 entry and replication in PBMCs. The title compound (1) has excellent oral bioavailability in rat, dog, and monkey.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::4525057c96c5a287b6aa0040fe6af55a https://pubmed.ncbi.nlm.nih.gov/11585438 Zobrazit plný text záznamu