title: Design and synthesis of novel N-hydroxy-dihydronaphthyridinones as potent and orally bioavailable HIV-1 integrase inhibitors.
abstract: HIV-1 integrase (IN) is one of three enzymes encoded by the HIV genome and is essential for viral replication, and HIV-1 IN inhibitors have emerged as a new promising class of therapeutics. Recently, we reported the synthesis of orally bioavailable azaindole hydroxamic acids that were potent inhibitors of the HIV-1 IN enzyme. Here we disclose the design and synthesis of novel tricyclic N-hydroxy-dihydronaphthyridinones as potent, orally bioavailable HIV-1 integrase inhibitors displaying excellent ligand and lipophilic efficiencies.
authors: Pfizer Global Research and Development, La Jolla Laboratories, 10770 Science Center Drive, San Diego, California 92121, United States. ted.w.johnson@pfizer.com
authors: Ted W
authors: TW
authors: Johnson
authors: Steven P
authors: SP
authors: Tanis
authors: Scott L
authors: SL
authors: Butler
authors: Deepak
authors: D
authors: Dalvie
authors: Dorothy M
authors: DM
authors: Delisle
authors: Klaus R
authors: KR
authors: Dress
authors: Erik J
authors: EJ
authors: Flahive
authors: Qiyue
authors: Q
authors: Hu
authors: Jon E
authors: JE
authors: Kuehler
authors: Atsuo
authors: A
authors: Kuki
authors: Wen
authors: W
authors: Liu
authors: Guy A
authors: GA
authors: McClellan
authors: Qinghai
authors: Q
authors: Peng
authors: Michael B
authors: MB
authors: Plewe
authors: Paul F
authors: PF
authors: Richardson
authors: Graham L
authors: GL
authors: Smith
authors: Jim
authors: J
authors: Solowiej
authors: Khanh T
authors: KT
authors: Tran
authors: Hai
authors: H
authors: Wang
authors: Xiaoming
authors: X
authors: Yu
authors: Junhu
authors: J
authors: Zhang
authors: Huichun
authors: H
authors: Zhu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004285:Dogs; D015195:Drug Design; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D022781:Hepatocytes / Q000378:metabolism; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008099:Liver / Q000378:metabolism; D008968:Molecular Conformation; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D009287:Naphthyridines