Indanylacetic acid derivatives carrying aryl-pyridyl and aryl-pyrimidinyl tail groups--new classes of PPAR gamma/delta and PPAR alpha/gamma/delta agonists.
Modulation of PPAR activities represents an attractive approach for the treatment of diabetes with associated cardiovascular complications. The indanylacetic acid structural motif has proven useful in the generation of potent and tunable PPAR ligands. Modification of the substituents on the linker and the heterocycle tail group allowed for the modulation of the selectivity at the different receptor subtypes. Compound 33 was evaluated in vivo, where it displayed the desired reduction of glucose levels and increase in HDL levels in various animal models.
Cantin
Louis-David
LD
Department of Chemistry Research, Bayer Pharmaceuticals Corporation, West Haven, CT 06516, USA. david.cantin.b@bayer.com
Liang
Sidney
S
Ogutu
Herbert
H
Iwuagwu
Christiana I
CI
Boakye
Ken
K
Bullock
William H
WH
Burns
Michael
M
Clark
Roger
R
Claus
Thomas
T
delaCruz
Fernando E
FE
Daly
Michelle
M
Ehrgott
Frederick J
FJ
Johnson
Jeffrey S
JS
Keiper
Christine
C
Livingston
James N
JN
Schoenleber
Robert W
RW
Shapiro
Jeffrey
J
Town
Christopher
C
Yang
Ling
L
Tsutsumi
Manami
M
Ma
Xin
X
D000085:Acetates / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006868:Hydrolysis; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D007189:Indans / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D008075:Lipoproteins, HDL / Q000097:blood; D051379:Mice; D047493:PPAR alpha / Q000819:agonists*; D047494:PPAR delta / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D051381:Rats; D011924:Rats, Zucker; D000077154:Rosiglitazone; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000627:therapeutic use
D000085:Acetates; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007189:Indans; D007202:Indicators and Reagents; D008075:Lipoproteins, HDL; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D002784:Cholesterol