Design and synthesis of boron-containing PDE4 inhibitors using soft-drug strategy for potential dermatologic anti-inflammatory application

  • Bioorg Med Chem Lett. 2010 Apr 1;20(7):2270-4. doi: 10.1016/j.bmcl.2010.02.010.
Yong-Kang Zhang  1 ,  Jacob J Plattner ,  Tsutomu Akama ,  Stephen J Baker ,  Vincent S Hernandez ,  Virginia Sanders ,  Yvonne Freund ,  Richard Kimura ,  Wei Bu ,  Karin M Hold ,  Xiao-Song Lu
Affiliations
  • 1. Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA. [email protected]
PMID: 20188549 DOI: 10.1016/j.bmcl.2010.02.010
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.

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