Identification of anxiolytic/nonsedative agents among indol-3- ylglyoxylamides acting as functionally selective agonists at the γ-aminobutyric acid-A (GABAA) α2 benzodiazepine receptor
Anxioselective agents may be identified among compounds binding selectively to the α2βxγ2 subtype of the γ-aminobutyric acid-A (GABAA)/central benzodiazepine receptor (BzR) complex and behaving as agonists or among compounds binding with comparable potency to various BzR subtypes but eliciting agonism only at the α2βxγ2 receptor. Because of subtle steric differences among BzR subtypes, the latter approach has proved much more successful. A biological screening within the class of indol-3-ylglyoxylamides 1-3 allowed us to identify compounds 1c and 2b as potential anxiolytic/nonsedative agents showing α2 selective efficacy in vitro and anxioselective effects in vivo. According to molecular modeling studies, and consistently with SARs accumulated in the past decade, 5-NO2- and 5-H-indole derivatives would preferentially bind to BzR by placing the indole ring in the LDi and the L2 receptor binding sites, respectively.
Asymmetric Cross [10+2] Cycloadditions of 2-Alkylidene-1-indanones and Activated Alkenes under Phase-Transfer Catalysis
Isobenzofulvene species are versatile synthons in organic chemistry, which have been employed in diverse challenging higher-order cycloaddition reactions. Here, the first chemoselective and asymmetric cross [10+2] cycloaddition reaction between activated 2-alkylidene-1-indanones and a variety of electron-deficient alkenes has been developed, relying on the in situ generation of dearomative 1-hydroxyl isobenzofulvene anion intermediates under the catalysis of a newly designed bulky cinchona-derived phase-transfer compound. An array of fused frameworks with multifunctionalities were generally furnished in excellent diastereo- and enantioselectivity, even at 1 mol % catalyst loadings.
Yang, Yang,Jiang, Ying,Du, Wei,Chen, Ying-Chun
p. 1754 - 1758
(2020/02/11)
Inter- and intramolecular hydroacylation of alkenes employing a bifunctional catalyst system
Based on a conceptually innovative bifunctional P,N ligand, an efficient protocol for the rhodium-catalyzed inter- and intramolecular hydroacylation of alkenes has been developed.
Vautravers, Nicolas R.,Regent, Damien D.,Breit, Bernhard
p. 6635 - 6637
(2011/06/27)
Aryl sulfonamido indane inhibitors of the Kv1.5 ion channel
A collection of aryl sulfonamido indanes based on the lead compound 1 was synthesized and evaluated for Kv1.5 inhibitory activity. Kv1.5 inhibitors have the potential to be atrium-selective agents for treatment of atrial fibrillation. (1R,2R)-1 has an IC50 of 0.033 μM against Kv1.5 and is selective against other cardiac ion channels, including hERG.
Gross, Michael F.,Beaudoin, Serge,McNaughton-Smith, Grant,Amato, George S.,Castle, Neil A.,Huang, Christine,Zou, Anruo,Yu, Weifeng
p. 2849 - 2853
(2008/02/11)
Synthesis of Isoquinolines from Indenes
A general procedure for the synthesis of isoquinolines from appropriately substituted indenes is described.Ozonolysis of the indenes followed by reductive workup gives intermediate homophthalaldehydes which are treated with ammonium hydroxide to give the isoquinolines.This "one-pot", three-step reaction sequence was applied to the formation of all of the mono-C-methyl-substituted isoquinolines in a regiospecific manner.The procedure is applicable to both electron-withdrawing and electron-donating substituents on the indene system.In this manner the 6- and 7-nitro-,-bromo-, and -iodoisoquinolines were prepared.
Miller, R. Bryan,Frincke, James M.
p. 5312 - 5315
(2007/10/02)
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