Synthesis of novel histamine H4 receptor antagonists

Charlotte A L Lane; Duncan Hay; Charles E Mowbray; Michael Paradowski; Matthew D Selby; Nigel A Swain; David H Williams

doi:10.1016/j.bmcl.2011.11.098

Synthesis of novel histamine H4 receptor antagonists

Bioorg Med Chem Lett. 2012 Jan 15;22(2):1156-9. doi: 10.1016/j.bmcl.2011.11.098. Epub 2011 Dec 1.

Authors

Charlotte A L Lane¹, Duncan Hay, Charles E Mowbray, Michael Paradowski, Matthew D Selby, Nigel A Swain, David H Williams

Affiliation

¹ Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, Sandwich, Kent CT13 9NJ, United Kingdom.

PMID: 22189138
DOI: 10.1016/j.bmcl.2011.11.098

Abstract

This letter describes the discovery and synthesis of a series of octahydropyrrolo[3,4-c]pyrrole based selective histamine hH4 receptor antagonists. The amidine compound 20 was found to be a potent and selective histamine H4 receptor antagonist with moderate clearance and a high volume of distribution.

MeSH terms

Animals
Azabicyclo Compounds / chemical synthesis
Azabicyclo Compounds / chemistry
Azabicyclo Compounds / pharmacology*
Crystallography, X-Ray
Dose-Response Relationship, Drug
Humans
Models, Molecular
Molecular Structure
Pyrrolidines / chemical synthesis
Pyrrolidines / chemistry
Pyrrolidines / pharmacology*
Rats
Receptors, G-Protein-Coupled / antagonists & inhibitors*
Receptors, Histamine
Receptors, Histamine H4
Stereoisomerism
Structure-Activity Relationship

Substances

Azabicyclo Compounds
HRH4 protein, human
Pyrrolidines
Receptors, G-Protein-Coupled
Receptors, Histamine
Receptors, Histamine H4