Controlling Ca²⁺ Permeable α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors with Photochromic Ion Channel Blockers

Abstract

Ionotropic glutamate receptors (iGluRs) play a critical role in normal brain function and neurodegenerative diseases. Development of light-dependent compounds would enable studies of iGluRs within intact mammalian neural tissue, as light is noninvasive and can be applied with high spatiotemporal precision. Here we develop a potent photochromic antagonist that selectively targets the Ca permeable AMPA-type of iGuRs, thus providing an important tool to study the contribution of AMPA-type iGluRs on neuronal activity.

Photoinduced Rapid Multicomponent Cascade Reaction of Aryldiazonium Salts with Unactivated Alkenes and TMSN3

“…Initially, 4-methoxybenzenediazonium tetrafluoroborate (1a), 1-amylene (2a), and TMSN 3 (3) were chosen as the starting substrates to optimize the reaction conditions (Table 1). When 4 mol % of Acr + MesClO 4 − (a visible-light photocatalyst) was used for the the target product (4a) was obtained in 34% yield.…”

“…We proposed that, initially, the photocatalyst PC-1 was photopromoted to the excited state producing the *PC-1 species (E red * = 2.06 V vs SCE). 19 Following this, a single electron transfer (SET) process occurred between TMSN 3 (3) and *PC-1 to produce the azido radical and PC-1radical anion. The oxidation potential of the free azide anion was found to be +1.32 V (NHE).…”

“…Aromatic azo compounds have been used for the preparation of dyes, pigments, therapeutic agents, food additives, and indicators (Figure ). The compounds can be obtained through the azo coupling reaction, Mills reaction, and Wallach reaction . However, these synthetic methods for forming the azo group suffer from various disadvantages.…”

Drug-Targeted Genomes: Mutability of Ion Channels and GPCRs

“…The publicly open NIH program announcement (PA-19-034) detailing the classification and identification of 390 understudied druggable genomes was utilized to acquire the list of 261 candidate genes encoding GPCRs and ion channels. The associated literature survey was performed until 9 December 2021, with emphasis on published title words with (1) ion channels since 2017 [4,5,[9][10][11][12][13][14]16,26,27,30,33,[39][40][41][42]44,[46][47][48]53,54,59,61,[69][70][71][72][73][74][75][76][77][78][79][80], (2) ion channel blockers since 2017 [41,[81][82][83][84][85][86][87][88][89][90]…”

Overview of Recent Strategic Advances in Medicinal Chemistry

“…For example, FMS(3)-gentamicin (133) was developed as a long-acting prodrug derivative by linking three (2-sulfo)-9-fluorenylmethoxycarbonyl (FMS) moieties to three amino moieties of gentamicin (132) to provide increased affinity for albumin. 191 134 is a fatty acid-like platinum(IV) prodrug designed to improve drug delivery via enhanced interaction with HSA.…”