Synthesis and evaluation of a 2-benzothiazolylphenylmethyl ether class of histamine H4 receptor antagonists

Olivier Labeeuw; Nicolas Levoin; Xavier Billot; Denis Danvy; Thierry Calmels; Stéphane Krief; Xavier Ligneau; Isabelle Berrebi-Bertrand; Philippe Robert; Jeanne-Marie Lecomte; Jean-Charles Schwartz; Marc Capet

doi:10.1016/j.bmcl.2016.09.049

Synthesis and evaluation of a 2-benzothiazolylphenylmethyl ether class of histamine H4 receptor antagonists

Bioorg Med Chem Lett. 2016 Nov 1;26(21):5263-5266. doi: 10.1016/j.bmcl.2016.09.049. Epub 2016 Sep 19.

Affiliations

¹ Bioprojet-Biotech, 4 rue du Chesnay Beauregard, BP 96205, 35762 Saint-Grégoire, France. Electronic address: [email protected].
² Bioprojet-Biotech, 4 rue du Chesnay Beauregard, BP 96205, 35762 Saint-Grégoire, France.

PMID: 27692832
DOI: 10.1016/j.bmcl.2016.09.049

Abstract

Synthesis and biological evaluation of a new class of histamine H₄ receptor ligands, distinct from the previously reported chemotypes, are described. A virtual screening of our corporate compound collection identified a hit with an undesired dual H3R/H4R activity. Chemical exploration led to the discovery of a more potent and selective 2-benzothiazolylphenylmethyl ether lead compound.

Keywords: Asthma; Atopic dermatitis; Histamine; Histamine H(4) receptor.

MeSH terms

Benzothiazoles / chemical synthesis*
Benzothiazoles / chemistry
Benzothiazoles / pharmacology
Cell Line
Drug Evaluation, Preclinical
Histamine Antagonists / chemical synthesis*
Histamine Antagonists / pharmacology*
Humans
Receptors, G-Protein-Coupled / antagonists & inhibitors*
Receptors, Histamine
Receptors, Histamine H4

Substances

Benzothiazoles
HRH4 protein, human
Histamine Antagonists
Receptors, G-Protein-Coupled
Receptors, Histamine
Receptors, Histamine H4