Synthesis and biological evaluation of pyrazoline analogues with beta-amino acyl group as dipeptidyl peptidase IV inhibitors.
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.
Jun
Mi Ae
MA
Drug Discovery Division, Korea Research Institute of Chemical Technology, Yuseong-Gu, Daejeon 305-600, Republic of Korea.
Park
Woul Seong
WS
Kang
Seung Kyu
SK
Kim
Ki Young
KY
Kim
Kwang Rok
KR
Rhee
Sang Dal
SD
Bae
Myung Ae
MA
Kang
Nam Sook
NS
Sohn
Sang-Kwon
SK
Kim
Sung Gyu
SG
Lee
Jie Oh
JO
Lee
Duck Hyung
DH
Cheon
Hyae Gyeong
HG
Kim
Sung Soo
SS
Ahn
Jin Hee
JH
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
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