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ID: ALA1914379
Journal: Bioorg Med Chem Lett
Title: Challenges of drug discovery in novel target space. The discovery and evaluation of PF-3893787: a novel histamine H4 receptor antagonist.
Authors: Mowbray CE, Bell AS, Clarke NP, Collins M, Jones RM, Lane CA, Liu WL, Newman SD, Paradowski M, Schenck EJ, Selby MD, Swain NA, Williams DH.
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.
CiteXplore: 21920751