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Brain penetrant liver X receptor (LXR) modulators based on a 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole core.

Authors :
Tice CM
Noto PB
Fan KY
Zhao W
Lotesta SD
Dong C
Marcus AP
Zheng YJ
Chen G
Wu Z
Van Orden R
Zhou J
Bukhtiyarov Y
Zhao Y
Lipinski K
Howard L
Guo J
Kandpal G
Meng S
Hardy A
Krosky P
Gregg RE
Leftheris K
McKeever BM
Singh SB
Lala D
McGeehan GM
Zhuang L
Claremon DA
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2016 Oct 15; Vol. 26 (20), pp. 5044-5050. Date of Electronic Publication: 2016 Aug 29.
Publication Year :
2016

Abstract

Liver X receptor (LXR) agonists have been reported to lower brain amyloid beta (Aβ) and thus to have potential for the treatment of Alzheimer's disease. Structure and property based design led to the discovery of a series of orally bioavailable, brain penetrant LXR agonists. Oral administration of compound 18 to rats resulted in significant upregulation of the expression of the LXR target gene ABCA1 in brain tissue, but no significant effect on Aβ levels was detected.<br /> (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
26
Issue :
20
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
27599745
Full Text :
https://doi.org/10.1016/j.bmcl.2016.08.089