TY - JOUR
T1 - Separation of α-glucosidase-inhibitory and liver X receptor-antagonistic activities of phenethylphenyl phthalimide analogs and generation of LXRα-selective antagonists
AU - Motoshima, Kazunori
AU - Noguchi-Yachide, Tomomi
AU - Sugita, Kazuyuki
AU - Hashimoto, Yuichi
AU - Ishikawa, Minoru
N1 - Funding Information:
The work described in this paper was partially supported by Grants-in-Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology, Japan, and the Japan Society for the Promotion of Science.
PY - 2009/7/15
Y1 - 2009/7/15
N2 - Liver X receptor (LXR) α/β dual agonists are candidate medicaments for the treatment of metabolic syndrome, because their biological actions include increasing cholesterol efflux mediated by LXRβ. However, their clinical application is currently limited by their enhancing effect on triglyceride (TG) synthesis mediated by LXRα. Combination of an LXRα-selective antagonist with an LXRα/β dual agonist may overcome this disadvantage. In the present work, structural development studies of phenethylphenyl phthalimide 9, which possesses LXRα/β dual-antagonistic activity and α-glucosidase-inhibitory activity, led to the LXRα-selective antagonist 23f. Specific α-glucosidase inhibitors were also obtained.
AB - Liver X receptor (LXR) α/β dual agonists are candidate medicaments for the treatment of metabolic syndrome, because their biological actions include increasing cholesterol efflux mediated by LXRβ. However, their clinical application is currently limited by their enhancing effect on triglyceride (TG) synthesis mediated by LXRα. Combination of an LXRα-selective antagonist with an LXRα/β dual agonist may overcome this disadvantage. In the present work, structural development studies of phenethylphenyl phthalimide 9, which possesses LXRα/β dual-antagonistic activity and α-glucosidase-inhibitory activity, led to the LXRα-selective antagonist 23f. Specific α-glucosidase inhibitors were also obtained.
KW - α-Glucosidase inhibitor
KW - LXR antagonist
KW - Thalidomide analog
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U2 - 10.1016/j.bmc.2009.05.066
DO - 10.1016/j.bmc.2009.05.066
M3 - Article
C2 - 19539483
AN - SCOPUS:67650077280
SN - 0968-0896
VL - 17
SP - 5001
EP - 5014
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 14
ER -