Pasqualetto, Gaia; Pileggi, Elisa; Schepelmann, Martin; Varricchio, Carmine; Rozanowska, Malgorzata; Brancale, Andrea; Bassetto, Marcella published their research in European Journal of Medicinal Chemistry on December 15 ,2021. The article was titled 《Ligand-based rational design, synthesis and evaluation of novel potential chemical chaperones for opsin》.Electric Literature of C6H12N2O The article contains the following contents:
Inherited blinding diseases retinitis pigmentosa (RP) and a subset of Leber’s congenital amaurosis (LCA) are caused by the misfolding and mistrafficking of rhodopsin mols., which aggregate and accumulate in the endoplasmic reticulum (ER), leading to photoreceptor cell death. One potential therapeutic strategy to prevent the loss of photoreceptors in these conditions is to identify opsin-binding compounds that act as chem. chaperones for opsin, aiding its proper folding and trafficking to the outer cell membrane. Aiming to identify novel compounds with such effect, a rational ligand-based approach was applied to the structure of the visual pigment chromophore, 11-cis-retinal, and its locked analog 11-cis-6mr-retinal. Following mol. docking studies on the main chromophore binding site of rhodopsin, 49 novel compounds, e.g., I, were synthesized according to optimized one-to seven-step synthetic routes. These agents were evaluated for their ability to compete for the chromophore binding site of opsin, and their capacity to increase the trafficking of the P23H opsin mutant from the ER to the cell membrane. Different new mols. displayed an effect in at least one assay, acting either as chem. chaperones or as stabilizers of the 9-cis-retinal-rhodopsin complex. These compounds could provide the basis to develop novel therapeutics for RP and LCA. In the experiment, the researchers used many compounds, for example, Piperidine-4-carboxamide(cas: 39546-32-2Electric Literature of C6H12N2O)
Piperidine-4-carboxamide(cas: 39546-32-2) belongs to anime. Halogenation, in which one or more hydrogen atoms of an amine is replaced by a halogen atom, occurs with chlorine, bromine, and iodine, as well as with some other reagents, notably hypochlorous acid (HClO). With primary amines the reaction proceeds in two stages, producing N-chloro- and N,N-dichloro-amines, RNHCl and RNCl2, respectively. With tertiary amines, an alkyl group may be displaced by a halogen.Electric Literature of C6H12N2O
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem