title: Design, synthesis, and structure-activity relationship of carbamate-tethered aryl propanoic acids as novel PPARalpha/gamma dual agonists.
abstract: We have developed a new class of PPARalpha/gamma dual agonists, which show excellent agonistic activity in PPARalpha/gamma transactivation assay. In particular, (R)-9d was identified as a potent PPARalpha/gamma dual agonist with EC(50)s of 0.377 microM in PPARalpha and 0.136 microM in PPARgamma, respectively. Interestingly, the structure-activity relationship revealed that the stereochemistry of the identified PPARalpha/gamma dual agonists significantly affects their agonistic activities in PPARalpha than in PPARgamma.
authors.affiliation: College of Pharmacy, Seoul National University, Sillim-dong, Seoul, Republic of Korea.
authors.forename: Nam-Jung
authors.initials: NJ
authors.lastname: Kim
authors.forename: Kwang-Ok
authors.initials: KO
authors.lastname: Lee
authors.forename: Bon-Woong
authors.initials: BW
authors.lastname: Koo
authors.forename: Funan
authors.initials: F
authors.lastname: Li
authors.forename: Ja-Kyung
authors.initials: JK
authors.lastname: Yoo
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Park
authors.forename: Kyung-Hoon
authors.initials: KH
authors.lastname: Min
authors.forename: Joong In
authors.initials: JI
authors.lastname: Lim
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Jin-Kwan
authors.initials: JK
authors.lastname: Kim
authors.forename: Young-Ger
authors.initials: YG
authors.lastname: Suh
mesh_terms: D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D011422:Propionates / Q000737:chemistry*; D000077154:Rosiglitazone; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000494:pharmacology; D015533:Transcriptional Activation
chemical_list: D002219:Carbamates; D010080:Oxazoles; D047493:PPAR alpha; D047495:PPAR gamma; D011422:Propionates; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C029658:propionic acid; D005998:Glycine; C500085:muraglitazar