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  • Title: The discovery of novel 5,6,5- and 5,5,6-tricyclic pyrrolidines as potent and selective DPP-4 inhibitors.
    Author: Cox JM, Chu HD, Kuethe JT, Gao YD, Scapin G, Eiermann G, He H, Li X, Lyons KA, Metzger J, Petrov A, Wu JK, Xu S, Sinha-Roy R, Weber AE, Biftu T.
    Journal: Bioorg Med Chem Lett; 2016 Jun 01; 26(11):2622-6. PubMed ID: 27106708.
    Abstract:
    Novel potent and selective 5,6,5- and 5,5,6-tricyclic pyrrolidine dipeptidyl peptidase IV (DPP-4) inhibitors were identified. Structure-activity relationship (SAR) efforts focused on improving the intrinsic DPP-4 inhibition potency, increasing protease selectivity, and demonstrating clean ion channel and cytochrome P450 profiles while trying to achieve a pharmacokinetic profile suitable for once weekly dosing in humans.
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