title: Discovery of β-aminoacyl containing thiazolidine derivatives as potent and selective dipeptidyl peptidase IV inhibitors.
abstract: A series of β-aminoacyl containing thiazolidine derivatives was synthesized and evaluated for their ability to inhibit DPP-IV. Several thiazolidine derivatives with an acid moiety were found to be potent DPP-IV inhibitors. Among them, compound 2da is the most active in this series with an IC(50) value of 1 nM, and it showed excellent selectivity over DPP-IV related enzymes including DPP-2, DPP-8, and DPP-9. Compound 2da is chemically and metabolically stable, and showed no CYP inhibition, hERG binding or cytotoxicity. Compound 2db, an ester prodrug of 2da, showed good in vivo DPP-IV inhibition after oral administration in rat and dog models.
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Yuseong-Gu, Daejeon, Republic of Korea.
authors.forename: Woul Seong
authors.initials: WS
authors.lastname: Park
authors.forename: Seung Kyu
authors.initials: SK
authors.lastname: Kang
authors.forename: Mi Ae
authors.initials: MA
authors.lastname: Jun
authors.forename: Mi Sik
authors.initials: MS
authors.lastname: Shin
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Kim
authors.forename: Sang Dal
authors.initials: SD
authors.lastname: Rhee
authors.forename: Myung Ae
authors.initials: MA
authors.lastname: Bae
authors.forename: Min Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Kwang Rok
authors.initials: KR
authors.lastname: Kim
authors.forename: Nam Sook
authors.initials: NS
authors.lastname: Kang
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Yoo
authors.forename: Jie Oh
authors.initials: JO
authors.lastname: Lee
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Song
authors.forename: Peter
authors.initials: P
authors.lastname: Silinski
authors.forename: Stephen Edward
authors.initials: SE
authors.lastname: Schneider
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Ahn
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018360:Crystallography, X-Ray; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D051381:Rats; D053778:Thiazolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D053778:Thiazolidines