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Amphipathic 3-phenyl-7-propylbenziscoxazoles;: human PPaR γ, δ and α agonists

被引：48
作者：
Adams, AD
Yuen, W
Hu, Z
Santini, C
Jones, AB
MacNaul, KL
Berger, JP
Doebber, TW
Moller, DE
机构：
[1] Merck & Co Inc, Merck Res Labs, Dept Basic Chem, Rahway, NJ 07065 USA
[2] Merck & Co Inc, Merck Res Labs, Dept Mol Endocrinol, Rahway, NJ 07065 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 05期
关键词：
D O I：
10.1016/S0960-894X(02)01029-6
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of amphipathic 3-phenylbenzisoxazoles were found to be potent agonists of human PPARalpha, gamma and delta. The optimization of acid proximal structure for in vitro and in vivo potency is described. Results of po dosed efficacy studies in the db/db mouse model of type 2 diabetes showed efficacy equal or superior to Rosiglitazone in correcting hyperglycemia and hyper-triglyceridemia. Good functional receptor selectivity for PPARalpha and gamma over PPARdelta can be obtained. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：931 / 935
页数：5
相关论文
共 26 条
  • [1] Post-prandial metabolism of triglyceride-rich lipoproteins in non-insulin-dependent diabetic patients before and after bezafibrate treatment
    Attia, N
    Durlach, V
    Roche, D
    Paul, JL
    Soni, T
    Zahouani, A
    Landron, F
    Labrousse, F
    Leutenegger, M
    GirardGloba, A
    [J]. EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 1997, 27 (01) : 55 - 63
  • [2] Novel peroxisome proliferator-activated receptor (PPAR) γ and PPARδ ligands produce distinct biological effects
    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
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (10) : 6718 - 6725
  • [3] Design and synthesis of 2-methyl-2-{4-[2-(5-methyl-2-aryloxazol-4-yl)ethoxy]phenoxy}propionic acids:: A new class of dual PPARα/γ agonists
    Brooks, DA
    Etgen, GJ
    Rito, CJ
    Shuker, AJ
    Dominianni, SJ
    Warshawsky, AM
    Ardecky, R
    Paterniti, JR
    Tyhonas, J
    Karanewsky, DS
    Kauffman, RF
    Broderick, CL
    Oldham, BA
    Montrose-Rafizadeh, C
    Winneroski, LL
    Faul, MM
    McCarthy, JR
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (13) : 2061 - 2064
  • [4] Burger A, 1991, Prog Drug Res, V37, P287
  • [5] CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099
  • [6] DURRINGTON PN, 1990, J CARDIOVASC PHARM, V16, pS30
  • [7] ELBRECHT, 1999, JBC, V274, P7913
  • [8] Hepatic failure in a patient taking rosiglitazone
    Forman, LM
    Simmons, DA
    Diamond, RH
    [J]. ANNALS OF INTERNAL MEDICINE, 2000, 132 (02) : 118 - 121
  • [9] Micronized fenofibrate: A new fibric acid hypolipidemic agent
    Guay, DRP
    [J]. ANNALS OF PHARMACOTHERAPY, 1999, 33 (10) : 1083 - 1103
  • [10] Elevated serum triglyceride levels and long-term mortality in patients with coronary heart disease - The Bezafibrate Infarction Prevention (BIP) Registry
    Haim, M
    Benderly, M
    Brunner, D
    Behar, S
    Graff, E
    Reicher-Reiss, H
    Goldbourt, U
    [J]. CIRCULATION, 1999, 100 (05) : 475 - 482
123