Design and synthesis of novel N-sulfonyl-2-indole carboxamides as potent PPAR-gamma binding agents with potential application to the treatment of osteoporosis.
The synthesis and structure-activity relationships of a novel series of N-sulfonyl-2-indole carboxamides that bind to peroxisome proliferator-activated receptor gamma (PPAR-gamma) are reported. Chemical optimization of the series led to the identification of 4q (IC(50)=50 nM) as a potent binding agent of PPAR-gamma. Also reported is preliminary cell based data suggesting the use of these compounds in the treatment of osteoporosis.
Hopkins
Corey R
CR
Procter and Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Road, Mason OH 45040, USA. Corey.Hopkins@sanofi-aventis.com
O'neil
Steven V
SV
Laufersweiler
Michael C
MC
Wang
Yili
Y
Pokross
Matthew
M
Mekel
Marlene
M
Evdokimov
Artem
A
Walter
Richard
R
Kontoyianni
Maria
M
Petrey
Maria E
ME
Sabatakos
Georgios
G
Roesgen
Jeff T
JT
Richardson
Eloise
E
Demuth
Thomas P
TP
D016475:3T3 Cells; D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D015195:Drug Design; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D010024:Osteoporosis / Q000188:drug therapy*; D047495:PPAR gamma / Q000378:metabolism*
D000577:Amides; D007211:Indoles; D047495:PPAR gamma