118939-52-9Relevant academic research and scientific papers
C5-Alkyl-2-methylurea-substituted pyridines as a new class of glucokinase activators
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.
supporting information, p. 1284 - 1289 (2015/02/02)
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.
Method for producing 1-substituted 5-hydroxypyrazoles
-
, (2008/06/13)
A process for preparing compounds of the formula I in which R1is hydrogen, an aliphatic group having 1-8 carbon atoms, C1-C6-alkoxycarbonyl, C1-C6-alkylthiocarbonyl or a cyclic ring system having 3-14 ring atoms, and R2is hydrogen, an aliphatic group having 1-8 carbon atoms, or R1and R2together with the carbon atom to which they are bound form a cyclic or bicyclic ring system having 3-14 ring atoms, comprises the preparation of compounds of the formula II ?in which R3and R4are readily detachable groups and R1and R2are as defined above, as starting materials or intermediates and the cyclization of these under suitable reaction conditions to give compounds of the formula I.
