97998-46-4Relevant academic research and scientific papers
KINETIC STUDIES ON THE AMINOLYSIS OF 1-(TRIMETHYLSILYL)ETHYL ARENESULPHONATES IN ACETONITRILE AND METHANOL
Oh, Hyuck Keun,Shin, Chul Ho,Park, Hyoung Yeon,Lee, Ikchoon
, p. 359 - 363 (1994)
Nucleophilic substitution reactions of 1-(trimethylsilyl)ethyl arenesulphonates with anilines and benzylamines in acetonitrile and methanol at 65.0 deg C were studied.The cross-interaction constants, ρXZ, between substituents in the nucleophile (X) and leaving group (Z) are relatively small (0.10 for XC6H4NH2 in MeCN) but similar to those for other SN2 processes at a secondary carbon atom.This provides further evidence for an approximately constant, loose SN2 transition state at a secondary carbon regardless of the size of the Cα substituent.The transition-state variations with substituents X and Z are in accord with that expected from the positive ρXZ value observed: a stronger nucleophile and/or nucleofuge leads to an earlier transition state, i. e. a lower degree of bond making and breaking.
The Discovery and Hit-to-Lead Optimization of Tricyclic Sulfonamides as Potent and Efficacious Potentiators of Glycine Receptors
Bregman, Howard,Simard, Jeffrey R.,Andrews, Kristin L.,Ayube, Shawn,Chen, Hao,Gunaydin, Hakan,Guzman-Perez, Angel,Hu, Jiali,Huang, Liyue,Huang, Xin,Krolikowski, Paul H.,Lehto, Sonya G.,Lewis, Richard T.,Michelsen, Klaus,Pegman, Pamela,Plant, Matthew H.,Shaffer, Paul L.,Teffera, Yohannes,Yi, Shuyan,Zhang, Maosheng,Gingras, Jacinthe,DiMauro, Erin F.
, p. 1105 - 1125 (2017/02/19)
Current pain therapeutics suffer from undesirable psychotropic and sedative side effects, as well as abuse potential. Glycine receptors (GlyRs) are inhibitory ligand-gated ion channels expressed in nerves of the spinal dorsal horn, where their activation is believed to reduce transmission of painful stimuli. Herein, we describe the identification and hit-to-lead optimization of a novel class of tricyclic sulfonamides as allosteric GlyR potentiators. Initial optimization of high-throughput screening (HTS) hit 1 led to the identification of 3, which demonstrated ex vivo potentiation of glycine-activated current in mouse dorsal horn neurons from spinal cord slices. Further improvement of potency and pharmacokinetics produced in vivo proof-of-concept tool molecule 20 (AM-1488), which reversed tactile allodynia in a mouse spared-nerve injury (SNI) model. Additional structural optimization provided highly potent potentiator 32 (AM-3607), which was cocrystallized with human GlyRα3cryst to afford the first described potentiator-bound X-ray cocrystal structure within this class of ligand-gated ion channels (LGICs).
Saturated abnormal NHC-gold(I) complexes: Synthesis and catalytic activity
Manzano, Ruben,Rominger, Frank,Hashmi, A. Stephen K.
supporting information, p. 2199 - 2203 (2013/05/21)
New saturated abnormal N-heterocyclic carbene complexes of gold(I) have been prepared by a 1,3-dipolar cycloaddition of an in situ generated azomethine ylide with an isocyanogold(I) choride. A series of different substituents on the nitrogen atom of the 1
Synthetic Application of Cyanoaminosilanes as Azomethine Ylide Equivalents
Padwa, Albert,Chen, Yon-Yih,Dent, William,Nimmesgern, Hildegard
, p. 4006 - 4014 (2007/10/02)
A series of α-cyanoaminosilanes have been found to act as azomethine ylide equivalents.Treatment of these compounds with silver fluoride in the presence of electron-dificient alkynes and olefins gives substituted pyrroles and pyrrolidines in high yield.It was found that N-benzyl-N-(cyanomethyl)-N-amine undergoes stereospecific cycloaddition with dimethyl fumarate and maleate.The stereospecificity of the reaction is consistent with a concerted cycloaddition reaction.The cycloaddition behavior of an unsymmetrically substituted α-cyanosilylamine with methyl propiolate was also examined and found to react with high overall regioselectivity.The synthetic utility of cyanoaminosilanes as azomethine ylide equivalents was demonstrated by the preparation of a Reniera isoindole alkaloid.The key step in the synthesis involved the reaction of 2-methyl-3-methoxyquinone with N-methyl-N-(cyanomethyl)-N-amine in the presence of silver fluoride to give 2,5-dimethyl-6-methoxy-2H-isoindole-4,7-dione in good yield.
