Chatzopoulou, Maria; Emer, Enrico; Lecci, Cristina; Rowley, Jessica A.; Casagrande, Anne-Sophie; Moir, Lee; Squire, Sarah E.; Davies, Stephen G.; Harriman, Shawn; Wynne, Graham M.; Wilson, Francis X.; Davies, Kay E.; Russell, Angela J. published the artcile< Decreasing HepG2 Cytotoxicity by Lowering the Lipophilicity of Benzo[d]oxazolephosphinate Ester Utrophin Modulators>, Computed Properties of 112-63-0, the main research area is benzoxazolephosphinate ester synthesis lipophilicity hepatotoxicity utrophin Duchenne muscular dystrophy.
Utrophin modulation is a disease-modifying therapeutic strategy for Duchenne muscular dystrophy that would be applicable to all patient populations. To improve the suboptimal profile of ezutromid, the first-in-class clin. candidate, a second generation of utrophin modulators bearing a phosphinate ester moiety was developed. This modification significantly improved the physicochem. and ADME properties, but one of the main lead mols. was found to have dose-limiting hepatotoxicity. In this work we describe how less lipophilic analogs retained utrophin modulatory activity in a reporter gene assay, up-regulated utrophin protein in dystrophic mouse muscle cells, but also had improved physicochem. and ADME properties. Notably, ClogP was found to directly correlate with pIC50 in HepG2 cells, hence leading to a potentially safer toxicol. profiles in this series. Compound 21 showed a balanced profile (H2K EC50: 4.17μM, solubility: 477μM, mouse hepatocyte T1/2 > 240 min) and increased utrophin protein 1.6-fold in a Western blot assay.
ACS Medicinal Chemistry Letters published new progress about Cytotoxicity. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Computed Properties of 112-63-0.
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics