1.
Bioorg Med Chem Lett
; 13(10): 1801-4, 2003 May 19.
Article
in English
| MEDLINE
| ID: mdl-12729668
ABSTRACT
A series of 5-aryl thiazolidine-2,4-diones containing 4-phenoxyphenyl side chains was designed, synthesized, and evaluated for PPAR agonist activities. One such compound 28 exhibited comparable levels of glucose correction to rosiglitazone in the db/db mouse type 2 diabetes animal model.
Subject(s)
Hypoglycemic Agents/chemical synthesis , Receptors, Cytoplasmic and Nuclear/agonists , Thiazolidinediones/chemical synthesis , Thiazolidinediones/pharmacokinetics , Transcription Factors/agonists , Animals , Blood Glucose/drug effects , Diabetes Mellitus, Type 2/drug therapy , Disease Models, Animal , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/pharmacology , Inhibitory Concentration 50 , Mice , Structure-Activity Relationship , Thiazolidinediones/pharmacology
2.
Bioorg Med Chem Lett
; 13(7): 1277-80, 2003 Apr 07.
Article
in English
| MEDLINE
| ID: mdl-12657263
ABSTRACT
Beginning with the weakly active lead structure 1, a new series of hPPAR agonists was developed. In vivo glucose and triglyceride lowering activity was obtained by homologation and oxamination to 3, then conversion to substituted benzisoxazoles 4 and 5. Further manipulation afforded benzofurans 6 and 7. Compound 7 was of comparable potency as a glucose and triglyceride lowering agent in insulin resistant rodents to BRL 49653.
