title: Exploration of piperidine-4-yl-aminopyrimidines as HIV-1 reverse transcriptase inhibitors. N-Phenyl derivatives with broad potency against resistant mutant viruses.
abstract: Further investigation of the recently reported piperidine-4-yl-aminopyrimidine class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) has been carried out. Thus, preparation of a series of N-phenyl piperidine analogs resulted in the identification of 3-carboxamides as a particularly active series. Analogs such as 28 and 40 are very potent versus wild-type HIV-1 and a broad range of NNRTI-resistant mutant viruses. Synthesis, structure-activity relationship (SAR), clearance data, and crystallographic evidence for the binding motif are discussed.
authors.affiliation: Roche R&D Center China, Shanghai, China. gordon.tang@roche.com
authors.forename: Guozhi
authors.initials: G
authors.lastname: Tang
authors.forename: Denis J
authors.initials: DJ
authors.lastname: Kertesz
authors.forename: Minmin
authors.initials: M
authors.lastname: Yang
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Lin
authors.forename: Zhanguo
authors.initials: Z
authors.lastname: Wang
authors.forename: Wentao
authors.initials: W
authors.lastname: Li
authors.forename: Zongxing
authors.initials: Z
authors.lastname: Qiu
authors.forename: Junli
authors.initials: J
authors.lastname: Chen
authors.forename: Jianghua
authors.initials: J
authors.lastname: Mei
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Taraneh
authors.initials: T
authors.lastname: Mirzadegan
authors.forename: Seth F
authors.initials: SF
authors.lastname: Harris
authors.forename: Armando G
authors.initials: AG
authors.lastname: Villaseñor
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fretland
authors.forename: William L
authors.initials: WL
authors.lastname: Fitch
authors.forename: Julie Qi
authors.initials: JQ
authors.lastname: Hang
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Heilek
authors.forename: Klaus
authors.initials: K
authors.lastname: Klumpp
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D010880:Piperidines; D011743:Pyrimidines; C034821:4-aminopyrimidine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase