Synthesis and anti-diabetic activity of (RS)-2-ethoxy-3-{4-[2-(4-trifluoro-methanesulfonyloxy-phenyl)-ethoxy]-phenyl}-propionic acid. 2006

Zhe-Feng Cai, and Quan Liu, and Ping-Ping Li, and Zong-Ru Guo, and Zhu-Fang Shen
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

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.

UI MeSH Term Description Entries
D007004 Hypoglycemic Agents Substances which lower blood glucose levels. Antidiabetic,Antidiabetic Agent,Antidiabetic Drug,Antidiabetics,Antihyperglycemic,Antihyperglycemic Agent,Hypoglycemic,Hypoglycemic Agent,Hypoglycemic Drug,Antidiabetic Agents,Antidiabetic Drugs,Antihyperglycemic Agents,Antihyperglycemics,Hypoglycemic Drugs,Hypoglycemic Effect,Hypoglycemic Effects,Hypoglycemics,Agent, Antidiabetic,Agent, Antihyperglycemic,Agent, Hypoglycemic,Agents, Antidiabetic,Agents, Antihyperglycemic,Agents, Hypoglycemic,Drug, Antidiabetic,Drug, Hypoglycemic,Drugs, Antidiabetic,Drugs, Hypoglycemic,Effect, Hypoglycemic,Effects, Hypoglycemic
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007333 Insulin Resistance Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS. Insulin Sensitivity,Resistance, Insulin,Sensitivity, Insulin
D008813 Mice, Inbred ICR An inbred strain of mouse that is used as a general purpose research strain, for therapeutic drug testing, and for the genetic analysis of CARCINOGEN-induced COLON CANCER. Mice, Inbred ICRC,Mice, ICR,Mouse, ICR,Mouse, Inbred ICR,Mouse, Inbred ICRC,ICR Mice,ICR Mice, Inbred,ICR Mouse,ICR Mouse, Inbred,ICRC Mice, Inbred,ICRC Mouse, Inbred,Inbred ICR Mice,Inbred ICR Mouse,Inbred ICRC Mice,Inbred ICRC Mouse
D010666 Phenylpropionates Derivatives of 3-phenylpropionic acid, including its salts and esters.
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D001786 Blood Glucose Glucose in blood. Blood Sugar,Glucose, Blood,Sugar, Blood
D001859 Bone Neoplasms Tumors or cancer located in bone tissue or specific BONES. Bone Cancer,Cancer of Bone,Cancer of the Bone,Neoplasms, Bone,Bone Neoplasm,Neoplasm, Bone
D005951 Glucose Tolerance Test A test to determine the ability of an individual to maintain HOMEOSTASIS of BLOOD GLUCOSE. It includes measuring blood glucose levels in a fasting state, and at prescribed intervals before and after oral glucose intake (75 or 100 g) or intravenous infusion (0.5 g/kg). Intravenous Glucose Tolerance,Intravenous Glucose Tolerance Test,OGTT,Oral Glucose Tolerance,Oral Glucose Tolerance Test,Glucose Tolerance Tests,Glucose Tolerance, Oral
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

Related Publications

Zhe-Feng Cai, and Quan Liu, and Ping-Ping Li, and Zong-Ru Guo, and Zhu-Fang Shen
October 2008, Acta crystallographica. Section E, Structure reports online,
Zhe-Feng Cai, and Quan Liu, and Ping-Ping Li, and Zong-Ru Guo, and Zhu-Fang Shen
August 1973, Experientia,
Zhe-Feng Cai, and Quan Liu, and Ping-Ping Li, and Zong-Ru Guo, and Zhu-Fang Shen
January 1953, Revista brasileira de gastroenterologia,
Zhe-Feng Cai, and Quan Liu, and Ping-Ping Li, and Zong-Ru Guo, and Zhu-Fang Shen
March 2013, Acta crystallographica. Section E, Structure reports online,
Zhe-Feng Cai, and Quan Liu, and Ping-Ping Li, and Zong-Ru Guo, and Zhu-Fang Shen
November 1981, Radioisotopes,
Zhe-Feng Cai, and Quan Liu, and Ping-Ping Li, and Zong-Ru Guo, and Zhu-Fang Shen
November 1981, Radioisotopes,
Zhe-Feng Cai, and Quan Liu, and Ping-Ping Li, and Zong-Ru Guo, and Zhu-Fang Shen
November 2010, Acta crystallographica. Section E, Structure reports online,
Zhe-Feng Cai, and Quan Liu, and Ping-Ping Li, and Zong-Ru Guo, and Zhu-Fang Shen
August 1979, Journal of medicinal chemistry,
Zhe-Feng Cai, and Quan Liu, and Ping-Ping Li, and Zong-Ru Guo, and Zhu-Fang Shen
May 1995, Farmaco (Societa chimica italiana : 1989),
Zhe-Feng Cai, and Quan Liu, and Ping-Ping Li, and Zong-Ru Guo, and Zhu-Fang Shen
January 1985, Arzneimittel-Forschung,
Copied contents to your clipboard!