Design, synthesis, and structure-activity relationships of piperidine and dehydropiperidine carboxylic acids as novel, potent dual PPARalpha/gamma agonists.
Several series of substituted dehydropiperidine and piperidine-4-carboxylic acid analogs have been designed and synthesized as novel, potent dual PPARalpha/gamma agonists. The SAR of these series of analogs is discussed. A rare double bond migration occurred during the basic hydrolysis of the alpha,beta-unsaturated dehydropiperidine esters 12, and the structures of the migration products were confirmed through a series of 2D NMR experiments.
Ye
Xiang-Yang
XY
Metabolic Diseases Chemistry, Bristol-Myers Squibb R&D, PO Box 5400, Princeton, NJ 08543-5400, USA. xiang-yang.ye@bms.com
Li
Yi-Xin
YX
Farrelly
Dennis
D
Flynn
Neil
N
Gu
Liqun
L
Locke
Kenneth T
KT
Lippy
Jonathan
J
O'Malley
Kevin
K
Twamley
Celeste
C
Zhang
Litao
L
Ryono
Denis E
DE
Zahler
Robert
R
Hariharan
Narayanan
N
Cheng
Peter T W
PT
D001667:Binding, Competitive / Q000187:drug effects; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002264:Carboxylic Acids; D047493:PPAR alpha; D047495:PPAR gamma; D010880:Piperidines