125068-08-8Relevant academic research and scientific papers
Discovery of Cytochrome P450 4F11 Activated Inhibitors of Stearoyl Coenzyme A Desaturase
Winterton, Sarah E.,Capota, Emanuela,Wang, Xiaoyu,Chen, Hong,Mallipeddi, Prema L.,Williams, Noelle S.,Posner, Bruce A.,Nijhawan, Deepak,Ready, Joseph M.
, p. 5199 - 5221 (2018/06/13)
Stearoyl-CoA desaturase (SCD) catalyzes the first step in the conversion of saturated fatty acids to unsaturated fatty acids. Unsaturated fatty acids are required for membrane integrity and for cell proliferation. For these reasons, inhibitors of SCD represent potential treatments for cancer. However, systemically active SCD inhibitors result in skin toxicity, which presents an obstacle to their development. We recently described a series of oxalic acid diamides that are converted into active SCD inhibitors within a subset of cancers by CYP4F11-mediated metabolism. Herein, we describe the optimization of the oxalic acid diamides and related N-acyl ureas and an analysis of the structure-activity relationships related to metabolic activation and SCD inhibition.
Tetrahydroisoquinoline derivatives
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, (2014/02/10)
Disclosed are compounds of formula (I) : wherein, R1 represents hydroxy or C1 6 alkoxy;, R2 and R3 are the same or different and are C1 6 alkyl or C3 6 alkenyl or -NR2R3 represents a 5-membered (optionally containing an oxygen atom adjacent to the nitrogen) or a 6-membered ring, which ring optionally contains one unit of unsaturation and which is unsubstituted or substituted by hydroxy, oxo, optionally substituted methylidene, -COR4(where R4 is C1 6 alkyl, aryl or ar(C1 6)alkyl) or =NOR5 (where R5 is C1 6 alkyl);, X represents a direct bond, -CH2- or -CH2O;, Ar represents a substituted phenyl moiety, and physiologically acceptable salts thereof. Also described are methods for their preparation and pharmaceutical formulations thereof. The compounds are Kappa agonists.
