title: Design and synthesis of boron-containing PDE4 inhibitors using soft-drug strategy for potential dermatologic anti-inflammatory application.
abstract: PDE4 inhibitors are a validated approach as anti-inflammatory agents but are limited by systemic side effects including emesis. We report a soft-drug strategy incorporating a carboxylic ester group into boron-containing PDE4 inhibitors leading to the discovery of a series of benzoxaborole compounds with good potency (for example IC(50)=47 nM of compound 2) and low emetic activity. These compounds are intended for dermatological use further limiting possible systemic side effects.
authors.affiliation: Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA. yzhang@anacor.com
authors.forename: Yong-Kang
authors.initials: YK
authors.lastname: Zhang
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Plattner
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Akama
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Baker
authors.forename: Vincent S
authors.initials: VS
authors.lastname: Hernandez
authors.forename: Virginia
authors.initials: V
authors.lastname: Sanders
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Freund
authors.forename: Richard
authors.initials: R
authors.lastname: Kimura
authors.forename: Wei
authors.initials: W
authors.lastname: Bu
authors.forename: Karin M
authors.initials: KM
authors.lastname: Hold
authors.forename: Xiao-Song
authors.initials: XS
authors.lastname: Lu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D001895:Boron / Q000097:blood / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D004423:Ear / Q000473:pathology; D004487:Edema / Q000188:drug therapy; D006801:Humans; D051379:Mice; D058988:Phosphodiesterase 4 Inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D058988:Phosphodiesterase 4 Inhibitors; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D001895:Boron