Synthesis and DP-IV inhibition of cyano-pyrazoline derivatives as potent anti-diabetic agents.
A new series of cyano-pyrazoline derivatives with secondary amine at P-2 site was synthesized through achiral and chiral synthetic methods and evaluated for their ability to inhibit dipeptidyl peptidase IV (DP-IV). Compound 5i revealed good in vivo efficacy (ED50: 4.1 mg/kg; in vivo DP-IV inhibition). Also chiral derivative (11b) having (S)-configuration of compound 5i was found to be more potent.
Ahn
Jin Hee
JH
Medicinal Science Division, Korea Research Institute of Chemical Technology, Yusung, Taejon 305-600, South Korea. jhahn@krict.re.kr
Kim
Hye-Min
HM
Jung
Sun Ho
SH
Kang
Seung Kyu
SK
Kim
Kwang Rok
KR
Rhee
Sang Dal
SD
Yang
Sung-Don
SD
Cheon
Hyae Gyeong
HG
Kim
Sung Soo
SS
D000818:Animals; D018938:Caco-2 Cells; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013552:Swine
D007004:Hypoglycemic Agents; D011480:Protease Inhibitors; D011720:Pyrazoles; C415802:DP IV-related protease, human; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases