441356-34-9Relevant 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.
METHODS FOR SYNTHESIZING GLYCINOLS, GLYCEOLLINS I AND II, COMPOSITIONS OF SELECTED INTERMEDIATES, AND THERAPEUTIC USES THEREOF
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, (2011/06/26)
Two distinct methods are disclosed and claimed for synthesizing glyceollin I plus glyceollin II as a mixture and as their pure forms. Stereochemical isomers and various synthetic intermediates are also synthesized and claimed for their novel compositions of matter. All compounds and their mixtures are claimed for use in formulations that are useful to treat or prevent cancer, or that have utility as selective estrogen receptor modulators, such formulations including enhanced or medical foods, dietary supplements and ethical pharmaceutical agents.
Biomimetic syntheses and antiproliferative activities of racemic, natural (-), and unnnatural (+) glyceollin i
Khupse, Rahul S.,Sarver, Jeffrey G.,Trendel, Jill A.,Bearss, Nicole R.,Reese, Michael D.,Wiese, Thomas E.,Boue, Stephen M.,Burow, Matthew E.,Cleveland, Thomas E.,Bhatnagar, Deepak,Erhardt, Paul W.
experimental part, p. 3506 - 3523 (2011/07/30)
A 14-step biomimetic synthetic route to glyceollin I (1.5% overall yield) was developed and deployed to produce the natural enantiomeric form in soy, its unnatural stereoisomer, and a racemic mixture. Enantiomeric excess was assessed by asymmetric NMR shift reagents and chiral HPLC. Antiproliferative effects were measured in human breast, ovarian, and prostate cancer cell lines, with all three chiral forms exhibiting growth inhibition (GI) in the low to mid μM range for all cells. The natural enantiomer, and in some cases the racemate, gave significantly greater GI than the unnatural stereoisomer for estrogen receptor positive (ER+) versus ER- breast/ovarian cell lines as well as for androgen receptor positive (AR+) versus AR - prostate cancer cells. Surprisingly, differences between ER + and ER- cell lines were not altered by media estrogen conditions. These results suggest the antiproliferative mechanism of glyceollin I stereoisomers may be more complicated than strictly ER interactions.
PHENOXYALKANOIC ACID COMPOUND
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Page/Page column 39, (2008/06/13)
The present invention provides a compound represented by the formula: wherein each symbol is as defined in the specification. Since the compound of the present invention has superior hypoglycemic action and superior hypolipidemic action, it is useful as an agent for the prophylaxis or treatment of diabetes, hyperlipidemia, impaired glucose tolerance and the like.
THERAPEUTIC AGENT FOR DIABETES
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Page/Page column 156-157, (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 197-198, (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.
ALKANOIC ACID DERIVATIVES, PROCESS FOR THEIR PRODUCTION AND USE THEREOF
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Page/Page column 56, (2008/06/13)
An alkanoic acid derivative useful as a prophylactic or therapeutic agent of diabetes mellitus, hyperlipidemia, impaired glucose tolerance and the like can be provided by a compound represented by the formula wherein R1 is an optionally substituted 5-membered aromatic heterocyclic group; X is a bond and the like; Q is a divalent hydrocarbon group having 1 to 20 carbon atoms; Y is a bond and the like; ring A is an aromatic ring optionally further having 1 to 3 substituents; Z is -(CH2)n-Z1- (n is an integer of 1 to 8 and Z1 is an oxygen atom and the like) and the like; ring B is a pyridine ring optionally further having 1 to 3 substituents, and the like; U is a bond and the like; W is a divalent hydrocarbon group having 1 to 20 carbon atoms; and R3 is -OH and the like, provided that, when ring B is a benzene ring optionally further having 1 to 3 substituents, U should be a bond, or a salt thereof.
