title: Discovery of oxazole-based PDE4 inhibitors with picomolar potency.
abstract: Optimization of oxazole-based PDE4 inhibitors has led to the discovery of a series of quinolyl oxazoles, with 4-benzylcarboxamide and 5-α-aminoethyl groups which exhibit picomolar potency against PDE4. Selectivity profiles and in vivo biological activity are also reported.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA. rongze.kuang@merck.com
authors.forename: Rongze
authors.initials: R
authors.lastname: Kuang
authors.forename: Ho-Jane
authors.initials: HJ
authors.lastname: Shue
authors.forename: Li
authors.initials: L
authors.lastname: Xiao
authors.forename: David J
authors.initials: DJ
authors.lastname: Blythin
authors.forename: Neng-Yang
authors.initials: NY
authors.lastname: Shih
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Danlin
authors.initials: D
authors.lastname: Gu
authors.forename: John
authors.initials: J
authors.lastname: Schwerdt
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.forename: Pauline C
authors.initials: PC
authors.lastname: Ting
authors.forename: Jianhua
authors.initials: J
authors.lastname: Cao
authors.forename: Robert
authors.initials: R
authors.lastname: Aslanian
authors.forename: John J
authors.initials: JJ
authors.lastname: Piwinski
authors.forename: Daniel
authors.initials: D
authors.lastname: Prelusky
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.forename: Chander S
authors.initials: CS
authors.lastname: Celly
authors.forename: Motasim
authors.initials: M
authors.lastname: Billah
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000737:chemistry; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000737:chemistry* / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D058988:Phosphodiesterase 4 Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D003497:Cyclic N-Oxides; D010080:Oxazoles; D058988:Phosphodiesterase 4 Inhibitors; D011804:Quinolines; C459379:SCH 351591; D014409:Tumor Necrosis Factor-alpha; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4