Expansion of first-in-class drug candidates that sequester toxic all-Trans-retinal and prevent light-induced retinal degeneration was written by Zhang, Jianye;Dong, Zhiqian;Mundla, Sreenivasa Reddy;Hu, X. Eric;Seibel, William;Papoian, Ruben;Palczewski, Krzysztof;Golczak, Marcin. And the article was included in Molecular Pharmacology in 2015.Product Details of 13417-49-7 This article mentions the following:
All-trans-retinal, a retinoid metabolite naturally produced upon photoreceptor light activation, is cytotoxic when present at elevated levels in the retina. To lower its toxicity, two exptl. validated methods have been developed involving inhibition of the retinoid cycle and sequestration of excess of all-trans-retinal by drugs containing a primary amine group. We identified the first-in-class drug candidates that transiently sequester this metabolite or slow down its production by inhibiting regeneration of the visual chromophore, 11-cis-retinal. Two enzymes are critical for retinoid recycling in the eye. Lecithin:retinol acyltransferase (LRAT) is the enzyme that traps vitamin A (all-trans-retinol) from the circulation and photoreceptor cells to produce the esterified substrate for retinoid isomerase (RPE65), which converts all-trans-retinyl ester into 11-cis-retinol. Here we investigated retinylamine and its derivatives to assess their inhibitor/substrate specificities for RPE65 and LRAT, mechanisms of action, potency, retention in the eye, and protection against acute light-induced retinal degeneration in mice. We correlated levels of visual cycle inhibition with retinal protective effects and outlined chem. boundaries for LRAT substrates and RPE65 inhibitors to obtain critical insights into therapeutic properties needed for retinal preservation. In the experiment, the researchers used many compounds, for example, 5,6-Dihydro-2H-pyran-3-carbaldehyde (cas: 13417-49-7Product Details of 13417-49-7).
5,6-Dihydro-2H-pyran-3-carbaldehyde (cas: 13417-49-7) belongs to tetrahydropyran derivatives. Tetrahydropyran is a useful synthetic intermediate. Tetrahydropyranyl (THP-) ethers derived from the reaction of alcohols and dihydropyran are common intermediates in organic synthesis. The bismuth chloride-assisted cross-cyclization between homoallylic alcohols and epoxides provided various benzyl tetrahydropyran derivatives. The reaction afforded good yields of desired products and occurred under mild conditions.Product Details of 13417-49-7
Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics