Indole- and benzothiophene-based histamine H3 antagonists

Alejandro Santillan Jr; Kelly J McClure; Brett D Allison; Brian Lord; Jamin D Boggs; Kirsten L Morton; Anita M Everson; Diane Nepomuceno; Michael A Letavic; Alice Lee-Dutra; Timothy W Lovenberg; Nicholas I Carruthers; Cheryl A Grice

doi:10.1016/j.bmcl.2010.08.103

Indole- and benzothiophene-based histamine H3 antagonists

Bioorg Med Chem Lett. 2010 Nov 1;20(21):6226-30. doi: 10.1016/j.bmcl.2010.08.103. Epub 2010 Aug 27.

Authors

Alejandro Santillan Jr¹, Kelly J McClure, Brett D Allison, Brian Lord, Jamin D Boggs, Kirsten L Morton, Anita M Everson, Diane Nepomuceno, Michael A Letavic, Alice Lee-Dutra, Timothy W Lovenberg, Nicholas I Carruthers, Cheryl A Grice

Affiliation

¹ Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121-1126, United States.

PMID: 20843691
DOI: 10.1016/j.bmcl.2010.08.103

Abstract

Previous research on histamine H(3) antagonists has led to the development of a pharmacophore model consisting of a central phenyl core flanked by two alkylamine groups. Recent investigation of the replacement of the central phenyl core with heteroaromatic fragments resulted in the preparation of novel 3,5-, 3,6- and 3,7-substituted indole and 3,5-substituted benzothiophene analogs that demonstrate good to excellent hH(3) affinities. Select analogs were profiled in a rat pharmacokinetic model.

MeSH terms

Animals
Ether-A-Go-Go Potassium Channels / drug effects
Histamine H3 Antagonists / chemical synthesis*
Histamine H3 Antagonists / pharmacokinetics
Histamine H3 Antagonists / pharmacology*
Indicators and Reagents
Indoles / chemical synthesis*
Indoles / pharmacokinetics
Indoles / pharmacology*
Isomerism
Models, Molecular
Rats
Structure-Activity Relationship
Thiophenes / chemical synthesis*
Thiophenes / pharmacokinetics
Thiophenes / pharmacology*

Substances

Ether-A-Go-Go Potassium Channels
Histamine H3 Antagonists
Indicators and Reagents
Indoles
Thiophenes
benzothiophene