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Bioorg Med Chem Lett. 2014 Dec 1;24(23):5489-92. doi: 10.1016/j.bmcl.2014.10.013. Epub 2014 Oct 13.

The effect of pK(a) on pyrimidine/pyridine-derived histamine H4 ligands.

Author information

1
Janssen Pharmaceutical Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, United States.

Abstract

During the course of our efforts toward the discovery of human histamine H4 antagonists from a series of 2-aminiopyrimidines, it was noted that a 6-trifluoromethyl group dramatically reduced affinity of the series toward the histamine H4 receptor. This observation was further investigated by synthesizing a series of ligands that varied in pKa of the pyrimidine derived H4 ligands by over five orders of magnitude and the effect on histamine H4 affinity. This trend was then extended to the discovery of C-linked piperidinyl-2-amino pyridines as histamine H4 receptor antagonists.

KEYWORDS:

Aminopyrimidine; H(4); Histamine H(4); Pyridine; Pyrimidine; pK(a)

PMID:
25455490
DOI:
10.1016/j.bmcl.2014.10.013
[Indexed for MEDLINE]

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