title: Discovery of oral and inhaled PDE4 inhibitors.
abstract: The optimization of oxazole-based PDE4 inhibitor 1 has led to the identification of both oral (compound 16) and inhaled (compound 34) PDE4 inhibitors. Selectivity against PDE10/PDE11, off target screening, and in vivo activity in the rat are discussed.
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA. Electronic address: pauline.ting@merck.com.
authors.forename: Pauline C
authors.initials: PC
authors.lastname: Ting
authors.forename: Joe F
authors.initials: JF
authors.lastname: Lee
authors.forename: Rongze
authors.initials: R
authors.lastname: Kuang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Cao
authors.forename: Danlin
authors.initials: D
authors.lastname: Gu
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Liu
authors.forename: Robert G
authors.initials: RG
authors.lastname: Aslanian
authors.forename: Kung-I
authors.initials: KI
authors.lastname: Feng
authors.forename: Daniel
authors.initials: D
authors.lastname: Prelusky
authors.forename: James
authors.initials: J
authors.lastname: Lamca
authors.forename: Aileen
authors.initials: A
authors.lastname: House
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Phillips
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.forename: Daniel
authors.initials: D
authors.lastname: Lundell
authors.forename: Richard W
authors.initials: RW
authors.lastname: Chapman
authors.forename: Chander S
authors.initials: CS
authors.lastname: Celly
mesh_terms: D000284:Administration, Oral; D000818:Animals; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000737:chemistry* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006207:Half-Life; D001239:Inhalation; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D058988:Phosphodiesterase 4 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: D010080:Oxazoles; D058988:Phosphodiesterase 4 Inhibitors; D011804:Quinolines; D011392:Proline; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4
keywords: Asthma; COPD; PDE4 inhibitor