888740-63-4Relevant academic research and scientific papers
Structure-activity relationships and key structural feature of pyridyloxybenzene-acylsulfonamides as new, potent, and selective peroxisome proliferator-activated receptor (PPAR) γ Agonists
Rikimaru, Kentaro,Wakabayashi, Takeshi,Abe, Hidenori,Tawaraishi, Taisuke,Imoto, Hiroshi,Yonemori, Jinichi,Hirose, Hideki,Murase, Katsuhito,Matsuo, Takanori,Matsumoto, Mitsuharu,Nomura, Chisako,Tsuge, Hiroko,Arimura, Naoto,Kawakami, Kazutoshi,Sakamoto, Junichi,Funami, Miyuki,Mol, Clifford D.,Snell, Gyorgy P.,Bragstad, Kenneth A.,Sang, Bi-Ching,Dougan, Douglas R.,Tanaka, Toshimasa,Katayama, Nozomi,Horiguchi, Yoshiaki,Momose, Yu
, p. 3332 - 3358 (2012/07/14)
In our search for a novel class of non-TZD, non-carboxylic acid peroxisome proliferator-activated receptor (PPAR) γ agonists, we explored alternative lipophilic templates to replace benzylpyrazole core of the previously reported agonist 1. Introduction of a pentylsulfonamide group into arylpropionic acids derived from previous in-house PPARγ ligands succeeded in the identification of 2-pyridyloxybenzene-acylsulfonamide 2 as a lead compound. Docking studies of compound 2 suggested that a substituent para to the central benzene ring should be incorporated to effectively fill the Y-shaped cavity of the PPARγ ligand-binding domain (LBD). This strategy led to significant improvement of PPARγ activity. Further optimization to balance in vitro activity and metabolic stability allowed the discovery of the potent, selective and orally efficacious PPARγ agonist 8f. Structure-activity relationship study as well as detailed analysis of the binding mode of 8f to the PPARγ-LBD revealed the essential structural features of this series of ligands.
ARYLALKANOIC ACID DERIVATIVE
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, (2008/06/13)
A compound represented by the formula (I): wherein Ar is an optionally substituted aromatic ring; Xa, Xc, Ya, Yc, Z1 and Z2 are each a bond, O, S, -CO-, -CS-, - CR3 (OR4) -, -NR5-, -SO-, -SO2-, -CONR6- or -NR6CO- (wherein R3, R4, R5 and R6 are as defined in the specification); Xb and Yb are each a bond or a divalent hydrocarbon group having 1 to 20 carbon atoms; R1 is an optionally substituted hydrocarbon group; ring A is an optionally further substituted aromatic ring, provided that the ring should not be benzimidazole; n is an integer of 1 to 8; ring B is an optionally further substituted aromatic ring, provided that the ring should not be oxazole; W is a divalent saturated hydrocarbon group having 1 to 20 carbon atoms; and R2 is -OR8 or -NR9R10 (wherein R8, R9 and R10 are as defined in the specification) or a salt thereof, is useful as an agent for the prophylaxis or treatment of diabetes and the like.
THERAPEUTIC AGENT FOR DIABETES
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Page/Page column 98-99, (2008/06/13)
The present invention provides an agent for the prophylaxis or treatment of diabetes, which is associated with a ferwer side effects such as body weight gain, adipocyte accumulation, cardiac hypertrophy and the like, and which contains a compound represented by the formula: wherein each symbol is as defined in the specification, or a salt thereof or a prodrug thereof.
ARYLALKANOIC ACID DERIVATIVE
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Page/Page column 224, (2010/11/08)
A compound represented by the general formula (I): [wherein Ar represents an optionally substituted aromatic ring; Xa, Xc, Ya, Yc, Z1, and Z2 each represents a bond, O, S, -CO-, -CS-, -CR3(OR4)-, -NR5-, -SO-, -SO2-, -CONR6-, or -NR6CO- (R3, R4, R5, and R6 are as defined in the description); Xb and Yb each represents a bond or a C1-20 divalent hydrocarbon group; R1 represents an optionally substituted hydrocarbon group; ring A represents an aromatic ring (other than benzimidazole) which may be further substituted; n is an integer of 1-8; ring B represents an aromatic ring (other than oxazole) which may be further substituted; W represents a C1-20 divalent saturated hydrocarbon group; and R2 represents -OR8 or -NR9R10 (R8, R9, and R10 are as defined in the description)] or a salt of the compound. It is useful as a preventive/therapeutic agent for diabetes, etc.
