- C5-Alkyl-2-methylurea-substituted pyridines as a new class of glucokinase activators
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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.
- 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.
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supporting information
p. 1284 - 1289
(2015/02/02)
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- PYRIDIN-2-YL-AMINO-1,2,4-THIADIAZOLE DERIVATIVES AS GLUCOKINASE ACTIVATORS FOR THE TREATMENT OF DIABETES MELLITUS
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Provided are compounds of Formula (I): wherein R2, R3, R13, L and D2 are as defined in the specification, which are useful in the treatment and/or prevention of diseases or disorders mediated by deficient levels of glucokinase activity or which can be treated by activating glucokinase including, but not limited to, diabetes mellitus, impaired glucose tolerance, IFG (impaired fasting glucose) and IFG (impaired fasting glycemia), as well as other diseases and disorders such as those discussed herein
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Page/Page column 90-91; 94
(2009/05/29)
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- Method for producing 1-substituted 5-hydroxypyrazoles
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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.
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- 4-benzoyl-1-alkyl (alkenyl) - pyrazoles, composition containing them, herbicidal method of using them, and intermediate in their preparation
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Pyrazole derivatives of the formula I: STR1 wherein R represents a lower alkyl group or a lower alkenyl group atoms which may be substituted by halogen atom, X represents a halogen atom, a lower alkyl group, nitro group, cyano group, a lower alkylsulfonyl
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