Novel morpholine ketone analogs as potent histamine H3 receptor inverse agonists with wake activity.
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.
Discovery Research, Cephalon, Inc., West Chester, PA 19380, USA. bgsundar@yahoo.com
Babu G
BG
Sundar
Thomas R
TR
Bailey
Derek
D
Dunn
Greg A
GA
Hostetler
Sankar
S
Chatterjee
Edward R
ER
Bacon
Christoph
C
Yue
Dominique
D
Schweizer
Lisa D
LD
Aimone
John A
JA
Gruner
Jacquelyn
J
Lyons
Rita
R
Raddatz
Brigitte
B
Lesur
D000818:Animals; D004569:Electroencephalography; D017442:Histamine Agonists / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007659:Ketones / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D018100:Receptors, Histamine H3; D013329:Structure-Activity Relationship; D014851:Wakefulness / Q000187:drug effects*
D017442:Histamine Agonists; D007659:Ketones; D009025:Morpholines; D018100:Receptors, Histamine H3