Details

Autor(en) / Beteiligte

• Du, Xiaohui
• Hinklin, Ronald J
• Xiong, Yumei
• Dransfield, Paul
• Park, Jaehyeon
• Kohn, Todd J
• Pattaropong, Vatee
• Lai, SuJen
• Fu, Zice
• Jiao, Xianyun
• Chow, David
• Jin, Lixia
• Davda, Jasmine
• Veniant, Murielle M
• Anderson, Deborah A
• Baer, Brian R
• Bencsik, Josef R
• Boyd, Steven A
• Chicarelli, Mark Joseph
• Mohr, Peter J
• Wang, Bin
• Condroski, Kevin R
• DeWolf, Walter E
• Conn, Marion
• Tran, Thanhvien
• Yang, Jerry
• Aicher, Thomas D
• Medina, Julio C
• Coward, Peter
• Houze, Jonathan B

Titel

C5-Alkyl-2-methylurea-Substituted Pyridines as a New Class of Glucokinase Activators

Ist Teil von

• ACS medicinal chemistry letters, 2014-12, Vol.5 (12), p.1284-1289

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2014

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Glucokinase (GK) activators represent a class of type 2 diabetes therapeutics actively pursued due to the central role that GK plays in regulating glucose homeostasis. Herein we report a novel C5-alkyl-2-methylurea-substituted pyridine series of GK activators derived from our previously reported thiazolylamino pyridine series. Our efforts in optimizing potency, enzyme kinetic properties, and metabolic stability led to the identification of compound 26 (AM-9514). This analogue showed a favorable combination of in vitro potency, enzyme kinetic properties, acceptable pharmacokinetic profiles in preclinical species, and robust efficacy in a rodent PD model.