2. Academic Validation
  3. Challenges of drug discovery in novel target space. The discovery and evaluation of PF-3893787: a novel histamine H4 receptor antagonist

Challenges of drug discovery in novel target space. The discovery and evaluation of PF-3893787: a novel histamine H4 receptor antagonist

  • Bioorg Med Chem Lett. 2011 Nov 1;21(21):6596-602. doi: 10.1016/j.bmcl.2011.07.125.
Charles E Mowbray 1,  Andrew S Bell,  Nicholas P Clarke,  Michelle Collins,  Rhys M Jones,  Charlotte A L Lane,  Wai L Liu,  Sandra D Newman,  Michael Paradowski,  Emanuel J Schenck,  Mathew D Selby,  Nigel A Swain,  David H Williams
Affiliations

Affiliation

  • 1 Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, Sandwich, Kent CT13 9NJ, UK. Charlie.Mowbray@googlemail.com
PMID: 21920751 DOI: 10.1016/j.bmcl.2011.07.125
Abstract

We describe the development of novel benzimidazoles as small molecule histamine H4 receptor (H4R) antagonists and their profiling in rat early toxicity studies. The discovery and optimisation of a second series of pyrimidine based antagonists is then described culminating in the identification of the clinical development candidate 13 (PF-3893787). The pre-clinical profile of 13 (PF-3893787) is presented including the development of a translatable biomarker. Our pragmatic approach to target selection, safety assessment, and testing for efficacy faced numerous challenges and we share a number of lessons which the team learned and which will assist us and Others in future drug discovery projects.

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