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Bioorg Med Chem Lett. 2015 Feb 15;25(4):956-9. doi: 10.1016/j.bmcl.2014.12.027. Epub 2014 Dec 23.

Diaminopyrimidines, diaminopyridines and diaminopyridazines as histamine H4 receptor modulators.

Author information

1
Janssen Pharmaceutical Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, United States. Electronic address: bsavall@its.jnj.com.
2
Janssen Pharmaceutical Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, United States.

Abstract

Previously disclosed H4 receptor modulators, the triamino substituted pyridines and pyrimidines, contain a free primary amino (-NH2) group. In this Letter we demonstrate that an exocyclic amine (NH2) is not needed to maintain affinity, and also show a significant divergence in the SAR of the pendant diamine component. These des-NH2 azacycles also show a distinct functional spectrum, that appears to be influenced by the diamine component; in the case of the 1,3-amino pyrimidines, the preferred diamine is the amino pyrrolidine instead of the more common piperazines. Finally, we introduce 3,5-diamino pyridazines as novel histamine H4 antagonists.

KEYWORDS:

Antagonists; Histamine H(4); Pyridazine; Pyridine; Pyrimidine

PMID:
25595684
DOI:
10.1016/j.bmcl.2014.12.027
[Indexed for MEDLINE]

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