5-Aryl thiazolidine-2,4-diones as selective PPARgamma agonists.
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.
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. hiroo_koyama@merck.com
Hiroo
H
Koyama
Julia K
JK
Boueres
Wei
W
Han
Edward J
EJ
Metzger
Jeffrey P
JP
Bergman
Dominick F
DF
Gratale
Daniel J
DJ
Miller
Richard L
RL
Tolman
Karen L
KL
MacNaul
Joel P
JP
Berger
Thomas W
TW
Doebber
Kwan
K
Leung
David E
DE
Moller
James V
JV
Heck
Soumya P
SP
Sahoo
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; C089946:2,4-thiazolidinedione