Novel morpholine ketone analogs as potent histamine H3 receptor inverse agonists with wake activity

Babu G Sundar; Thomas R Bailey; Derek Dunn; Greg A Hostetler; Sankar Chatterjee; Edward R Bacon; Christoph Yue; Dominique Schweizer; Lisa D Aimone; John A Gruner; Jacquelyn Lyons; Rita Raddatz; Brigitte Lesur

doi:10.1016/j.bmcl.2012.01.004

Novel morpholine ketone analogs as potent histamine H3 receptor inverse agonists with wake activity

Bioorg Med Chem Lett. 2012 Feb 15;22(4):1546-9. doi: 10.1016/j.bmcl.2012.01.004. Epub 2012 Jan 10.

Authors

Babu G Sundar¹, Thomas R Bailey, Derek Dunn, Greg A Hostetler, Sankar Chatterjee, Edward R Bacon, Christoph Yue, Dominique Schweizer, Lisa D Aimone, John A Gruner, Jacquelyn Lyons, Rita Raddatz, Brigitte Lesur

Affiliation

¹ Discovery Research, Cephalon, Inc., West Chester, PA 19380, USA. bgsundar@yahoo.com

PMID: 22297111
DOI: 10.1016/j.bmcl.2012.01.004

Abstract

Structure-activity relationship on a novel ketone class of H(3)R antagonists/inverse agonists is disclosed. Compound 4 showed excellent target potency, selectivity and brain penetration. Evaluation of antagonist 4 in the rat EEG/EMG model demonstrated robust wake activity thereby establishing preclinical proof of concept.

MeSH terms

Animals
Electroencephalography
Histamine Agonists / chemistry
Histamine Agonists / pharmacology*
Humans
Ketones / chemistry*
Ketones / pharmacology
Male
Molecular Structure
Morpholines / chemistry*
Morpholines / pharmacology
Rats
Receptors, Histamine H3*
Structure-Activity Relationship
Wakefulness / drug effects*

Substances

Histamine Agonists
Ketones
Morpholines
Receptors, Histamine H3