Synthesis and anti-diabetic activity of (RS)-2-ethoxy-3-{4-[2-(4-trifluoro-methanesulfonyloxy-phenyl)-ethoxy]-phenyl}-propionic acid.
OBJECTIVE
To synthesize and study the anti-diabetic activity of (RS)-2-ethoxy-3-{4-[2-(4-trifluoromethanesulfonyloxy-phenyl)-ethoxy]-phenyl}-propionic acid (compound I).


METHODS
Compound I was prepared in 6 steps, using 4-(2-hydroxy-ethyl)-phenol as the starting material. The in vitro selectivity and potency of target compound I, rosiglitazone and WY-14643 on human PPARalpha and PPARgamma were determined in reporter gene assays. In vivo, rosiglitazone and compound I were administered orally to KK(Ay) mice for 14 d. Insulin tolerance tests and oral glucose tolerance tests were performed on the 10th and 14th day of treatment, respectively. At the end of the treatment, sera were collected for biochemical analysis.


RESULTS
In vitro, compound I significantly activated both PPARalpha and PPARgamma. In vivo, compound I corrected the impaired insulin and glucose tolerance of KK(Ay) mice, and produced a significant reduction in plasma triglyceride levels after 14 d of treatment. The effect produced was significant compared with the control group.


CONCLUSIONS
Both in vitro and in vivo anti-diabetic activity studies for compound I were conducted and the data suggest that this compound is a potentially effective anti-diabetic agent.
Cai
Zhe-Feng
ZF
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Liu
Quan
Q
Li
Ping-Ping
PP
Guo
Zong-Ru
ZR
Shen
Zhu-Fang
ZF
D000818:Animals; D001190:Arylsulfonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism*; D048068:PPAR-beta / Q000819:agonists / Q000378:metabolism*; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
C514869:2-ethoxy-3-(4-(2-(4-trifluoromethanesulfonyloxyphenyl)ethoxy)phenyl)propionic acid; D001190:Arylsulfonates; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D047493:PPAR alpha; D048068:PPAR-beta; D010666:Phenylpropionates; D011743:Pyrimidines; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone; C006253:pirinixic acid