Details

Autor(en) / Beteiligte

• 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

Titel

Discovery of Novel Tricyclic Heterocycles as Potent and Selective DPP‑4 Inhibitors for the Treatment of Type 2 Diabetes

Ist Teil von

• ACS medicinal chemistry letters, 2016-05, Vol.7 (5), p.498-501

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2016

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.