1160501-80-3Relevant academic research and scientific papers
Strategies for the modulation of phase II metabolism in a series of PKCε inhibitors
Clemens, Jeremy J.,Coon, Timothy,Busch, Brett B.,Asgian, Juliana L.,Hudson, Sarah,Termin, Andreas,Flores, Tina B.,Tran, Dao,Chiang, Peggy,Sperry, Sam,Gross, Ray,Abt, Jeffrey,Heim, Roger,Lechner, Sandra,Twin, Heather,Studley, John,Brenchley, Guy,Collier, Philip N.,Pierard, Francoise,Miller, Andrew,Mak, Chau,Dvornikovs, Vadims,Jimenez, Juan-Miguel,Stamos, Dean
, p. 3398 - 3402 (2014/07/22)
Extensive phase II metabolism of an advanced PKCε inhibitor resulted in sub-optimal pharmacokinetics in rat marked by elevated clearance. Synthesis of the O-glucuronide metabolite as a standard was followed by three distinct strategies to specifically temper phase II metabolic degradation of the parent molecule. In this study, it was determined that the introduction of proximal polarity to the primary alcohol generally curbed O-glucuronidation and improved PK and physical chemical properties while maintaining potency against the target. Utilization of a Jacobsen hydrolytic kinetic resolution to obtain optically enriched final compounds is also discussed.
[1H- PYRAZOLO [3, 4-B] PYRIDINE-4-YL] -PHENYLE OR -PYRIDIN-2-YLE DERIVATIVES AS PROTEIN KINASE C-THETA
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Page/Page column 163, (2009/07/17)
The present invention relates to compounds of formula (I) and (IA) useful as inhibitors of protein kinase (1a). The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions. (a) : in particular protein kinase C theta, wherein A and A' are independently -N- or -C(R+) -. Ring B is five- or six-membered saturated carbocyclic or heterocyclic R1, R2, R3, R4, R5, R6, R7, x and y are as described herein.
