1338075-42-5Relevant academic research and scientific papers
Rational Design and Optimization of a Novel Class of Macrocyclic Apoptosis Signal-Regulating Kinase 1 Inhibitors
Himmelbauer, Martin K.,Xin, Zhili,Jones, J. Howard,Enyedy, Istvan,King, Kristopher,Marcotte, Douglas J.,Murugan, Paramasivam,Santoro, Joseph C.,Hesson, Thomas,Spilker, Kerri,Johnson, Joshua L.,Luzzio, Michael J.,Gilfillan, Rab,De Turiso, Felix Gonzalez-Lopez
, p. 10740 - 10756 (2019)
Structural analysis of a known apoptosis signal-regulating kinase 1 (ASK1) inhibitor bound to its kinase domain led to the design and synthesis of the novel macrocyclic inhibitor 8 (cell IC50 = 1.2 μM). The profile of this compound was optimized for CNS penetration following two independent strategies: a rational design approach leading to 19 and a parallel synthesis approach leading to 26. Both analogs are potent ASK1 inhibitors in biochemical and cellular assays (19, cell IC50 = 95 nM; 26, cell IC50 = 123 nM) and have moderate to low efflux ratio (ER) in an MDR1-MDCK assay (19, ER = 5.2; 26, ER = 1.5). In vivo PK studies revealed that inhibitor 19 had moderate CNS penetration (Kpuu = 0.17) and analog 26 had high CNS penetration (Kpuu = 1.0).
ASK1 INHIBITING AGENTS
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Page/Page column 171; 177, (2018/09/08)
Provided are compounds of Formulas (I'), (I), (II') and (II), or pharmaceutically acceptable salts thereof, and methods for their use and production.
MACROCYCLIC INTEGRASE INHIBITORS
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Page/Page column 49, (2011/10/13)
Compound having Formula (I) and pharmaceutically acceptable salts or solvates thereof, their pharmaceutical formulations and use as HIV inhibitors.
