Pyridine-2-propanoic acids: Discovery of dual PPARalpha/gamma agonists as antidiabetic agents.
A series of novel pyridine-2-propanoic acids was synthesized. A structure-activity relationship study of these compounds led to the identification of potent dual PPARalpha/gamma agonists with varied isoform selectivity. Based on the results of efficacy studies in diabetic (db/db) mice, and the desired pharmacokinetic parameters, compound (S)-13 was selected for further profiling.
Humphries
Paul S
PS
Department of Diabetes Chemistry, Pfizer Global R&D, 10770 Science Center Drive, San Diego, CA 92121, USA. paul.humphries@pfizer.com <paul.humphries@pfizer.com>
Almaden
Jonathon V
JV
Barnum
Sandra J
SJ
Carlson
Thomas J
TJ
Do
Quyen-Quyen T
QQ
Fraser
James D
JD
Hess
Mary
M
Kim
Young H
YH
Ogilvie
Kathleen M
KM
Sun
Shaoxian
S
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D015394:Molecular Structure; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D011725:Pyridines; C023666:pyridine