Synthesis and biological activities of novel aryl indole-2-carboxylic acid analogs as PPARgamma partial agonists.
A series of novel aryl indole-2-carboxylic acids has been identified as potent selective PPARgamma modulators. Their chemical synthesis and in vitro activities are discussed. Compound 5 was selected for in vivo testing in the db/db mouse model of type 2 diabetes and resulted in reduction of hyperglycemia at comparable plasma exposure when compared to rosiglitazone.
Dropinski
James F
JF
Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. James_Dropinski@merck.com
Akiyama
Taro
T
Einstein
Monica
M
Habulihaz
Bahanu
B
Doebber
Tom
T
Berger
Joel P
JP
Meinke
Peter T
PT
Shi
Guo Q
GQ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002264:Carboxylic Acids; D004195:Disease Models, Animal; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D015394:Molecular Structure; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D017186:Titrimetry
D001786:Blood Glucose; D002264:Carboxylic Acids; D007211:Indoles; D047495:PPAR gamma; C058980:indole-2-carboxylic acid