Phenotypic Optimization of Urea-Thiophene Carboxamides To Yield Potent, Well Tolerated, and Orally Active Protective Agents against Aminoglycoside-Induced Hearing Loss was written by Chowdhury, Sarwat;Owens, Kelly N.;Herr, R. Jason;Jiang, Qin;Chen, Xinchao;Johnson, Graham;Groppi, Vincent E.;Raible, David W.;Rubel, Edwin W.;Simon, Julian A.. And the article was included in Journal of Medicinal Chemistry in 2018.Application of 16413-26-6 This article mentions the following:
Hearing loss is a major public health concern with no pharmaceutical intervention for hearing protection or restoration. Using zebrafish neuromast hair cells, a robust model for mammalian auditory and vestibular hair cells, we identified a urea-thiophene carboxamide, I (ORC-001), as protective against aminoglycoside antibiotic (AGA)-induced hair cell death. The 50% protection (HC50) concentration conferred by I is 3.2 娓璏 with protection against 200 娓璏 neomycin approaching 100%. Compound I was sufficiently safe and drug-like to validate otoprotection in an in vivo rat hearing loss model. We explored the structure-activity relationship (SAR) of this compound series to improve otoprotective potency, improve pharmacokinetic properties and eliminate off-target activity. We present the optimization of I to yield II (ORC-13661). Compound II protects mechanosensory hair cells with HC50 of 120 nM and demonstrates 100% protection in the zebrafish assay and superior physiochem., pharmacokinetic, and toxicol. properties, as well as complete in vivo protection in rats. In the experiment, the researchers used many compounds, for example, 3-Cyanophenylisocyanate (cas: 16413-26-6Application of 16413-26-6).
3-Cyanophenylisocyanate (cas: 16413-26-6) belongs to esters. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits. Acyl chlorides and acid anhydrides alcoholysis is another way to produce esters. Acyl chlorides and acid anhydrides react with alcohols to produce esters. Anydrous conditions are recommended since both acyl chlorides and acid anhydrides react with water.Application of 16413-26-6
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