Aryloxazolidinediones:: Identification of potent orally active PPAR dual α/γ agonists

被引：30

作者：

Desai, RC

Gratale, DF

Han, W

Koyama, H

Metzger, E

Lombardo, VK

MacNaul, KL

Doebber, TW

Berger, JP

Leung, K

Franklin, R

Moller, DE

Heck, JV

Sahoo, SP

机构：

[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck Res Labs, Dept Metab Disorders, Rahway, NJ 07065 USA

[3] Merck Res Labs, Dept Drug Metab, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 20期

关键词：

D O I：

10.1016/S0960-894X(03)00785-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel aryloxazolidine-2,4-diones was synthesized. A structure-activity relationship study of these compounds led to the identification of potent, orally active PPAR dual alpha/gamma agonists. Based on the results of efficacy studies in the db/db mice model of type 2 diabetes and the desired pharmacokinetic parameters, compound 12 was selected for further profiling. (C) 2003 Published by Elsevier Ltd.

引用

页码：3541 / 3544

页数：4

共 12 条

[1] Amphipathic 3-phenyl-7-propylbenziscoxazoles;: human PPaR γ, δ and α agonists [J].

Adams, AD ;

Yuen, W ;

Hu, Z ;

Santini, C ;

Jones, AB ;

MacNaul, KL ;

Berger, JP ;

Doebber, TW ;

Moller, DE .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (05) :931-935

[2] Novel peroxisome proliferator-activated receptor (PPAR) γ and PPARδ ligands produce distinct biological effects [J].

Berger, J ;

Leibowitz, MD ;

Doebber, TW ;

Elbrecht, A ;

Zhang, B ;

Zhou, GC ;

Biswas, C ;

Cullinan, CA ;

Hayes, NS ;

Li, Y ;

Tanen, M ;

Ventre, J ;

Wu, MS ;

Berger, GD ;

Mosley, R ;

Marquis, R ;

Santini, C ;

Sahoo, SP ;

Tolman, RL ;

Smith, RG ;

Moller, DE .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (10) :6718-6725

[3] 5-aryl thiazolidine-2,4-diones:: Discovery of PPAR dual α/γ agonists as antidiabetic agents [J].

Desai, RC ;

Han, W ;

Metzger, EJ ;

Bergman, JP ;

Gratale, DF ;

MacNaul, KL ;

Berger, JP ;

Doebber, TW ;

Leung, K ;

Moller, DE ;

Heck, JV ;

Sahoo, SP .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (16) :2795-2798

[4]

DESAI RC, 2002, Patent No. 6465497

[5] BENZYLOXAZOLIDINE-2,4-DIONES AS POTENT HYPOGLYCEMIC AGENTS [J].

DOW, RL ;

BECHLE, BM ;

CHOU, TT ;

CLARK, DA ;

HULIN, B ;

STEVENSON, RW .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (05) :1538-1544

[6] New drug targets for type 2 diabetes and the metabolic syndrome [J].

Moller, DE .

NATURE, 2001, 414 (6865) :821-827

[7] A novel insulin sensitizer acts as a coligand for peroxisome proliferator-activated receptor-α.: (PPAR-α) and PPAR-γ -: Effect of PPAR-α activation on abnormal lipid metabolism in liver of Zucker fatty rats [J].

Murakami, K ;

Tobe, K ;

Ide, T ;

Mochizuki, T ;

Ohashi, M ;

Akanuma, Y ;

Yazaki, Y ;

Kadowaki, T .

DIABETES, 1998, 47 (12) :1841-1847

[8] (3-substituted benzyl)thiazolidine-2,4-diones as structurally new antihyperglycemic agents [J].

Nomura, M ;

Kinoshita, S ;

Satoh, H ;

Maeda, T ;

Murakami, K ;

Tsunoda, M ;

Miyachi, H ;

Awano, K .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (04) :533-538

[9]

SAHOO SP, 1999, Patent No. 6008237

[10] IMPROVED GLUCOSE-TOLERANCE IN RATS TREATED WITH OXAZOLIDINEDIONES [J].

SCHNUR, RC ;

MORVILLE, M .

JOURNAL OF MEDICINAL CHEMISTRY, 1986, 29 (05) :770-778

← 1 2 →