1227610-18-5Relevant articles and documents
ARYL AND HETEROARYL ETHER DERIVATIVES AS LIVER X RECEPTOR β AGONISTS, COMPOSITIONS, AND THEIR USE
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, (2018/04/27)
Substituted aryl and heteroaryl ether compounds of the Formula (I) and pharmaceutically acceptable salts thereof, wherein X, R 1, R 2, R 3, L, R 4, L 1, Q, and R 5 are as defined herein. These compounds and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
Discovery of spirofused piperazine and diazepane amides as selective histamine-3 antagonists with in vivo efficacy in a mouse model of cognition
Brown, Dean G.,Bernstein, Peter R.,Griffin, Andrew,Wesolowski, Steve,Labrecque, Denis,Tremblay, Maxime C.,Sylvester, Mark,Mauger, Russell,Edwards, Phillip D.,Throner, Scott R.,Folmer, James J.,Cacciola, Joseph,Scott, Clay,Lazor, Lois A.,Pourashraf, Mehrnaz,Santhakumar, Vijayaratnam,Potts, William M.,Sydserff, Simon,Giguère, Pascall,Lévesque, Carine,Dasser, Mohammed,Groblewski, Thierry
, p. 733 - 758 (2014/03/21)
A new series of potent and selective histamine-3 receptor (H3R) antagonists was identified on the basis of an azaspiro[2.5]octane carboxamide scaffold. Many scaffold modifications were largely tolerated, resulting in nanomolar-potent compounds in the H3R functional assay. Exemplar compound 6s demonstrated a selective profile against a panel of 144 secondary pharmacological receptors, with activity at only σ2 (62% at 10 μM). Compound 6s demonstrated free-plasma exposures above the IC50 (～50×) with a brain-to-plasma ratio of ～3 following intravenous dosing in mice. At three doses tested in the mouse novel object recognition model (1, 3, and 10 mg/kg s.c.), 6s demonstrated a statistically significant response compared with the control group. This series represents a new scaffold of H3 receptor antagonists that demonstrates in vivo exposure and efficacy in an animal model of cognition.
