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Bioorg Med Chem Lett. 2010 Oct 1;20(19):5713-7. doi: 10.1016/j.bmcl.2010.08.009. Epub 2010 Aug 6.

Discovery of potent and selective histamine H3 receptor inverse agonists based on the 3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one scaffold.

Author information

1
F Hoffmann-La Roche Ltd, Pharmaceutical Research, Grenzacherstrasse, CH-4070 Basel, Switzerland. hans.richter@roche.com

Abstract

A novel series of potent histamine H(3) receptor inverse agonists based on the 3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one scaffold has been discovered. Several compounds display high selectivity over other histamine receptor subtypes and have favorable physicochemical properties, low potential for CYP450 enzyme inhibition and high metabolic stability in microsomal preparations. (R)-2-Cyclopropylmethyl-8-(1-isopropyl-piperidin-4-yloxy)-3-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (8t) showed good in vivo efficacy after per os application in an acute rat dipsogenia model of water intake.

PMID:
20801030
DOI:
10.1016/j.bmcl.2010.08.009
[Indexed for MEDLINE]

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