Novel N-substituted 4-hydrazino piperidine derivative as a dipeptidyl peptidase IV inhibitor.
A novel class of N-substituted 4-hydrazino piperidine derivatives were designed, synthesized and evaluated for DPP IV inhibition. The SAR studies on the N-substituted piperidine led to the discovery of compound 22e as a potent DPP IV inhibitor (IC(50) 88nM), which is highly selective over other peptidases. In vivo efficacy indicates that compound 22e stimulates insulin release in response to glucose load and improves glucose tolerance in n5-STZ and Zucker Diabetic Fatty (ZDF) rats.
Gupta
Ramesh C
RC
Medicinal Chemistry, Torrent Research Centre, Torrent Pharmaceuticals Ltd., Gandhinagar, Gujarat, India. rameshgupta@torrentpharma.com
Chhipa
Laxmikant
L
Mandhare
Appaji B
AB
Zambad
Shitalkumar P
SP
Chauthaiwale
Vijay
V
Nadkarni
Sunil S
SS
Dutt
Chaitanya
C
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D013329:Structure-Activity Relationship
D054873:Dipeptidyl-Peptidase IV Inhibitors; D006834:Hydrazines; D007004:Hypoglycemic Agents; D010880:Piperidines; D018819:Dipeptidyl Peptidase 4