title: Design and synthesis of novel N-sulfonyl-2-indole carboxamides as potent PPAR-gamma binding agents with potential application to the treatment of osteoporosis.
abstract: 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.
authors.affiliation: Procter and Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Road, Mason OH 45040, USA. Corey.Hopkins@sanofi-aventis.com
authors.forename: Corey R
authors.initials: CR
authors.lastname: Hopkins
authors.forename: Steven V
authors.initials: SV
authors.lastname: O'neil
authors.forename: Michael C
authors.initials: MC
authors.lastname: Laufersweiler
authors.forename: Yili
authors.initials: Y
authors.lastname: Wang
authors.forename: Matthew
authors.initials: M
authors.lastname: Pokross
authors.forename: Marlene
authors.initials: M
authors.lastname: Mekel
authors.forename: Artem
authors.initials: A
authors.lastname: Evdokimov
authors.forename: Richard
authors.initials: R
authors.lastname: Walter
authors.forename: Maria
authors.initials: M
authors.lastname: Kontoyianni
authors.forename: Maria E
authors.initials: ME
authors.lastname: Petrey
authors.forename: Georgios
authors.initials: G
authors.lastname: Sabatakos
authors.forename: Jeff T
authors.initials: JT
authors.lastname: Roesgen
authors.forename: Eloise
authors.initials: E
authors.lastname: Richardson
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Demuth
mesh_terms: 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*
chemical_list: D000577:Amides; D007211:Indoles; D047495:PPAR gamma