Ravula, Suchitra published the artcileLead Optimization of 5-Aryl Benzimidazolone- and Oxindole-Based AMPA Receptor Modulators Selective for TARP γ-8, Category: indole-building-block, the publication is ACS Medicinal Chemistry Letters (2018), 9(8), 821-826, database is CAplus and MEDLINE.
Glutamate mediates fast excitatory neurotransmission via ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The trafficking and gating properties of AMPA receptors (AMPARs) can be amplified by transmembrane AMPAR regulatory proteins (TARPs), which are often expressed in localized brain regions. Herein, the authors describe the discovery, lead optimization, and preclin. characterization of 5-arylbenzimidazolone and oxindole-based neg. modulators of AMPARs associated with TARP γ-8, the primary TARP found in hippocampus. High-throughput screen lead 4 (5-(o-tolyl)indolin-2-one) was optimized for potency and brain penetration to provide benzimidazolone 3, JNJ-55511118. Replacement of the benzimidazolone core in 3 with an oxindole mitigated reactive metabolite formation and led to the identification of 18 (5-[2-chloro-6-(trifluoromethoxy)phenyl]-7-methylindolin-2-one) (GluA1/γ-8 pIC50 = 9.7). Following oral dosing in rats, 18 demonstrated robust target engagement in hippocampus as assessed by ex vivo autoradiog. (ED50 = 0.6 mg/kg, plasma EC50 = 9 ng/mL).
ACS Medicinal Chemistry Letters published new progress about 837392-64-0. 837392-64-0 belongs to indole-building-block, auxiliary class Indoline,Boronic acid and ester,Amide,Boronate Esters, name is 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)indolin-2-one, and the molecular formula is C14H18BNO3, Category: indole-building-block.
Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles