title: Synthesis and biological evaluation of pyrazoline analogues with beta-amino acyl group as dipeptidyl peptidase IV inhibitors.
abstract: A series of pyrazoline derivatives with beta-amino acyl group were synthesized and evaluated for their ability to inhibit dipeptidyl peptidase IV. Several pyrazoline derivatives exhibited submicromolar inhibitory activities against DPP-IV. X-ray co-crystal structure of initial hit compound 1h was determined. Among this series, carboxylic acid substituted pyrazoline derivative 2u was the most active and greatly decreased the inhibitory activity toward CYP3A4 enzyme.
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Yuseong-Gu, Daejeon 305-600, Republic of Korea.
authors.forename: Mi Ae
authors.initials: MA
authors.lastname: Jun
authors.forename: Woul Seong
authors.initials: WS
authors.lastname: Park
authors.forename: Seung Kyu
authors.initials: SK
authors.lastname: Kang
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Kim
authors.forename: Kwang Rok
authors.initials: KR
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: Nam Sook
authors.initials: NS
authors.lastname: Kang
authors.forename: Sang-Kwon
authors.initials: SK
authors.lastname: Sohn
authors.forename: Sung Gyu
authors.initials: SG
authors.lastname: Kim
authors.forename: Jie Oh
authors.initials: JO
authors.lastname: Lee
authors.forename: Duck Hyung
authors.initials: DH
authors.lastname: Lee
authors.forename: Hyae Gyeong
authors.initials: HG
authors.lastname: Cheon
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Ahn
mesh_terms: D000588:Amines / Q000737:chemistry*; D018938:Caco-2 Cells; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D065692:Cytochrome P-450 CYP3A Inhibitors; D054873:Dipeptidyl-Peptidase IV Inhibitors; D011720:Pyrazoles; C031280:pyrazole; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human