Brain penetrant liver X receptor (LXR) modulators based on a 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole core.
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.
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Colin M
CM
Tice
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Paul B
PB
Noto
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Kristi Yi
KY
Fan
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Wei
W
Zhao
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Stephen D
SD
Lotesta
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Chengguo
C
Dong
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Andrew P
AP
Marcus
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Ya-Jun
YJ
Zheng
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Guozhou
G
Chen
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Zhongren
Z
Wu
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Rebecca
R
Van Orden
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Jing
J
Zhou
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Yuri
Y
Bukhtiyarov
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Yi
Y
Zhao
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Kerri
K
Lipinski
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Lamont
L
Howard
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Joan
J
Guo
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Geeta
G
Kandpal
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Shi
S
Meng
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Andrew
A
Hardy
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Paula
P
Krosky
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Richard E
RE
Gregg
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Katerina
K
Leftheris
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Brian M
BM
McKeever
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Suresh B
SB
Singh
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Deepak
D
Lala
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Gerard M
GM
McGeehan
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
Linghang
L
Zhuang
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
David A
DA
Claremon
D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D000071518:Liver X Receptors / Q000187:drug effects*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D015854:Up-Regulation
D064286:ATP Binding Cassette Transporter 1; D000071518:Liver X Receptors; D012333:RNA, Messenger; C577834:Abca1 protein, rat
Alzheimer’s disease; Brain; LXR; Structure-based drug design