Tricyclic aminopyrimidine histamine H4 receptor antagonists

Brad M Savall; Laurent Gomez; Frank Chavez; Michael Curtis; Steven P Meduna; Aaron Kearney; Paul Dunford; Jeffery Cowden; Robin L Thurmond; Cheryl Grice; James P Edwards

doi:10.1016/j.bmcl.2011.08.014

Tricyclic aminopyrimidine histamine H4 receptor antagonists

Bioorg Med Chem Lett. 2011 Nov 1;21(21):6577-81. doi: 10.1016/j.bmcl.2011.08.014. Epub 2011 Aug 19.

Authors

Brad M Savall¹, Laurent Gomez, Frank Chavez, Michael Curtis, Steven P Meduna, Aaron Kearney, Paul Dunford, Jeffery Cowden, Robin L Thurmond, Cheryl Grice, James P Edwards

Affiliation

¹ Johnson & Johnson Pharmaceutical Research & Development, LLC 3210 Merryfield Row, San Diego, CA 92121, USA. [email protected]

PMID: 21920744
DOI: 10.1016/j.bmcl.2011.08.014

Abstract

This report discloses the development of a series of tricyclic histamine H(4) receptor antagonists. Starting with a low nanomolar benzofuranopyrimidine HTS hit devoid of pharmaceutically acceptable properties, we navigated issues with metabolism and solubility to furnish a potent, stable and water soluble tricyclic histamine H(4) receptor antagonist with desirable physiochemical parameters which demonstrated efficacy a mouse ova model.

MeSH terms

Animals
Histamine Antagonists / chemistry
Histamine Antagonists / pharmacology*
Mice
Receptors, G-Protein-Coupled / antagonists & inhibitors*
Receptors, Histamine
Receptors, Histamine H4

Substances

Histamine Antagonists
Hrh4 protein, mouse
Receptors, G-Protein-Coupled
Receptors, Histamine
Receptors, Histamine H4