상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

Design, synthesis, and biological evaluation of a series of alkoxy-3-indolylacetic acids as peroxisome proliferator-activated receptor γ/δ agonists

Authors 

H J GimH LiJ H JeongS J LeeM K SungM Y SongB H ParkSoo Jin OhJ H RyuR Jeon

Publisher 

Elsevier

Issue Date 

2015

Citation 

Bioorganic & Medicinal Chemistry, vol. 23, no. 13, pp. 3322-3336

Keywords 

AgonistIndolylacetic acidMetabolic diseasePPAR

Abstract 

Abstract A series of alkoxy-3-indolylacetic acid analogs has been discovered as peroxisome proliferator-activated receptor (PPAR) agonists. Structure-activity relationship study indicated that PPARα/γ/δ activities were dependent on the nature of the hydrophobic group, the attachment position of the alkoxy linker to the indole ring, and N-alkylation of indole nitrogen. Some compounds presented significant PPARγ/δ activity and molecular modeling suggested their putative binding modes in the ligand binding domain of PPARγ. Of these, compound 51 was selected for in vivo study via an evaluation of microsomal stability in mouse and human liver. Compound 51 lowered the levels of fasting blood glucose, insulin, and HbA1c without gain in body weight in db/db mice. When compound 51 was treated, hepatic triglycerides level and the size of adipocytes in white adipose tissue of db/db mice were also reduced as opposed to treatment with rosiglitazone. Taken together, compound 51 shows high potential warranting further studies in models for diabetes and related metabolic disorders and may be in use as a chemical tool for the understanding of PPAR biology.

ISSN 

0968-0896

Link 

http://dx.doi.org/10.1016/j.bmc.2015.04.046

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)