159017-42-2Relevant articles and documents
Novel 5-substituted 2,4-thiazolidinedione and 2,4-oxazolidinedione derivatives as insulin sensitizers with antidiabetic activities
Momose, Yu,Maekawa, Tsuyoshi,Yamano, Tohru,Kawada, Mitsuru,Odaka, Hiroyuki,Ikeda, Hitoshi,Sohda, Takashi
, p. 1518 - 1534 (2007/10/03)
Two novel classes of 2,4-thiazolidinediones and 2,4-oxazolidinediones with an ω-(azolylalkoxyphenyl)alkyl substituent at the 5-position were prepared and their antidiabetic effects were evaluated in two genetically obese and diabetic animal models, KKAy mice and Wistar fatty rats. A large number of the 2,4-thia(oxa)zolidinediones showed potent glucose- and lipid-lowering activities. The antidiabetic activities of the 2,4-oxazolidinediones were superior to those of the 2,4-thiazolidinediones. Among the compounds, both enantiomers of 5-[3-[4-[2-(2-furyl)-5-methyl-4-oxazolylmethoxy]-3- methoxyphenyl]propyl]-2,4-oxazolidinedione (64), one of the most interesting compounds in terms of activity, were synthesized by using an asymmetric O-acetylation of the corresponding α-hydroxyvalerate (26) with immobilized lipase, followed by cyclization of the oxazolidinedione ring. (R)-(+)-64 showed more potent glucose-lowering activity (effective dose (ED)25 = 0.561 mg/kg/d) than (S)-(-)-64 (ED25 > 1.5 mg/kg/d) or pioglitazone (ED25 = 6 mg/kg/d) in KKAy mice. It also exhibited a 10-fold more potent antidiabetic activity (ED25 = 0.05 mg/kg/d) than pioglitazone (ED25 = 0.5 mg/kg/d) in Wistar fatty rats. The antidiabetic effects of this compound are considered to be due to its potent agonistic activity for peroxisome proliferator-activated receptor γ (EC50 = 8.87 nM).
Oxazolidinedione derivatives and their use
-
, (2008/06/13)
Novel 2,4-oxazolidinedione compounds of the formula: STR1 wherein R is a hydrocarbon residue or a heterocyclic group each of which may be substituted; Y is --CO--, --CH(OH)-- or --NR3 -- (wherein R3 is an alkyl group which may be substituted); m is 0 or 1; n is 0, 1 or 2; X is CH or N; A is bivalent straight or branched hydrocarbon chain residue having 1 to 7 carbon atoms; R1 and R2 each are hydrogen or an alkyl group, or R1 and R2 are combined with each other to form a 5- to 6-membered heterocyclic group optionally containing nitrogen; L and M each are hydrogen, or L and M are combined with each other to form a bond, or pharmaceutically acceptable salts thereof, having excellent hypoglycemic and hypolipidemic activities and are useful as anti-diabetics or hypolipidemic agents.
