1417715-76-4Relevant articles and documents
Discovery of Novel Tricyclic Heterocycles as Potent and Selective DPP-4 Inhibitors for the Treatment of Type 2 Diabetes
Wu, Wen-Lian,Hao, Jinsong,Domalski, Martin,Burnett, Duane A.,Pissarnitski, Dmitri,Zhao, Zhiqiang,Stamford, Andrew,Scapin, Giovanna,Gao, Ying-Duo,Soriano, Aileen,Kelly, Terri M.,Yao, Zuliang,Powles, Mary Ann,Chen, Shiying,Mei, Hong,Hwa, Joyce
, p. 498 - 501 (2016/06/01)
In our efforts to develop second generation DPP-4 inhibitors, we endeavored to identify distinct structures with long-acting (once weekly) potential. Taking advantage of X-ray cocrystal structures of sitagliptin and other DPP-4 inhibitors, such as alogliptin and linagliptin bound to DPP-4, and aided by molecular modeling, we designed several series of heterocyclic compounds as initial targets. During their synthesis, an unexpected chemical transformation provided a novel tricyclic scaffold that was beyond our original design. Capitalizing on this serendipitous discovery, we have elaborated this scaffold into a very potent and selective DPP-4 inhibitor lead series, as highlighted by compound 17c.