Optimization of 1,4-diazepan-2-one containing dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes.

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Liang GB, Qian X, Feng D, Biftu T, Eiermann G, He H, Leiting B, Lyons K, Petrov A, Sinha-Roy R, Zhang B, Wu J, Zhang X, Thornberry NA, Weber AE

Optimization of 1,4-diazepan-2-one containing dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes.

Bioorg Med Chem Lett. 2007 Apr 1;17(7):1903-7. Epub 2007 Jan 24.

PubMed ID

17291750 [ View in PubMed

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Abstract

Following the discovery of N-acyl-1,4-diazepan-2-one as a novel pharmacophore for potent and selective DPP-4 inhibitors, optimization of this new lead with different substitution on the seven-membered ring resulted in several highly potent and selective, orally bioavailable, and efficacious DPP-4 inhibitors, such as 3R-methyl-1-cyclopropyl-1,4-diazepan-2-one derivative 9i (DPP-4 IC(50)=8.0 nM) and 3R,6R-dimethyl-1,4-diazepan-2-one derivative 14a (DPP-4 IC(50)=9.7 nM).

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
(3R)-4-[(3R)-3-AMINO-4-(2,4,5-TRIFLUOROPHENYL)BUTANOYL]-3-METHYL-1,4-DIAZEPAN-2-ONE	Dipeptidyl peptidase 4	IC 50 (nM)	6.6	7.5	37	Details