- Synthesis and structure-activity relationships of novel zwitterionic compounds as peroxisome proliferator activated receptor α/γ dual agonists with improved physicochemical properties
-
We describe herein the design, syntheses and structure-activity relationships (SAR) of novel zwitter-ionic compounds as non-thiazolidinedion (TZD) based peroxisome proliferator activated receptor (PPAR) α/γ dual agonists. In the previous report, we obtained compound 1 showing potent PPARα/γ dual agonistic activities, together with a great glucose lowering effect in the db/db mice. However, this compound possessed fatal issues such as potent cytochrome P450 (CYP)3A4 direct inhibitory activity. Thus, we carried out the medicinal optimization to improve these while maintaining the potent PPAR agonistic activity. As a result, the issues were addressed by changing the furan ring to a low lipophilic 1,3,4-oxadiazole ring. Additionally, these oxadiazole derivatives exhibited a significant decrease in plasma glucose and plasma triglyceride levels without marked weight gain.
- Shibata, Yoshihiro,Kagechika, Katsuji,Yamaguchi, Mitsuhiro,Yoshikawa, Kenji,Chiba, Kiyoshi,Takano, Hiromichi,Akiyama, Chiyuki,Ono, Mayumi,Nishi, Mina,Kubo, Hideo,Kobayashi, Yoshimasa,Usui, Hiroyuki
-
p. 1248 - 1263
(2014/01/06)
-
- PHENOXYACETIC ACID DERIVATIVES AND DRUGS USING THE SAME
-
It is intended to provide a novel compound having an excellent agonism to PPARs α/γ and desirable properties as a drug. An agonist to peroxisome proliferator-activated receptors α/γ which is represented by the general formula (I) (wherein Q represents an optionally substituted benzene ring or pyridine ring; R1 and R2 represent each an optionally substituted phenyl group or a 5- to 6-membered aromatic heterocycle group; X, Y and Z independently represent each C, O, S or N; R3 to R9 represent each a hydrogen atom, a lower alkyl group, etc.; and n is an integer of from 0 to 3.
- -
-
Page/Page column 49-52
(2010/11/26)
-
- PYRAZOLE DERIVATIVES
-
A compound represented by the general formula (I), which is useful as a peroxisome proliferator-activated receptor α/γ agonist, a salt of the compound, and a solvate of either. (In the formula, X, Y, and Z each represents nitrogen or carbon; m is an integ
- -
-
Page/Page column 62-63
(2010/10/19)
-
- PHENOXYACETIC ACID DERIVATIVE AND MEDICINE CONTAINING THE SAME
-
Novel compounds having excellent PPAR α/γ agonist effects and having desirable properties for medicaments are provided. Peroxisome proliferator-activated receptor α/γ agonists of the general formula (I): (wherein Q is an optionally-substituted benzene or
- -
-
Page/Page column 31
(2010/11/25)
-