33695-67-9Relevant academic research and scientific papers
Design, Synthesis, and Pharmacological Evaluation of Novel β2/3 Subunit-Selective γ-Aminobutyric Acid Type A (GABAA) Receptor Modulators
Stadler, Marco,Monticelli, Serena,Seidel, Thomas,Luger, Denise,Salzer, Isabella,Boehm, Stefan,Holzer, Wolfgang,Schwarzer, Christoph,Urban, Ernst,Khom, Sophia,Langer, Thierry,Pace, Vittorio,Hering, Steffen
, p. 317 - 341 (2018/11/02)
Subunit-selective modulation of γ-aminobutyric acid type A receptors (GABAAR) is considered to exert fewer side effects compared to unselective clinically used drugs. Here, the β2/3 subunit-selective GABAAR modulators valerenic acid (VA) and loreclezole (LOR) guided the synthesis of novel subunit-selective ligands with simplified structures. We studied their effects on GABAARs expressed in Xenopus laevis oocytes using two-microelectrode voltage clamp technique. Five compounds showed significantly more efficacious modulation of GABA-evoked currents than VA and LOR with retained potency and selectivity. Compound 18 [(E)-2-Cyano-3-(2,4-dichlorophenyl)but-2-enamide] induced the highest maximal modulation of GABA-induced chloride currents (Emax: 3114 ± 242%), while 12 [(Z)-3-(2,4-dichlorophenyl)but-2-enenitrile] displayed the highest potency (EC50: 13 ± 2 μM). Furthermore, in hippocampal neurons 12 facilitated phasic and tonic GABAergic inhibition, and in vivo studies revealed significantly more potent protection against pentylenetetrazole (PTZ)-induced seizures compared to VA and LOR. Collectively, compound 12 constitutes a novel, simplified, and subunit-selective GABAAR modulator with low-dose anticonvulsant activity.
PHARMACEUTICAL COMPOSITION FOR MODULATING THE RESPONSE OF A GABA-A RECEPTOR
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Paragraph 0135; 0168-0169, (2019/06/27)
The present invention relates to a pharmaceutical composition for use as a medicament and to the use of the pharmaceutical composition for modulating the response of a GABAA receptor and the treatment of conditions like insomnia, anxiety, cardiac disease and/or epilepsy. Furthermore, the present invention refers to new active agents suitable for said pharmaceutical compositions.
INHIBITORS OF BACTERIAL TYPE III SECRETION SYSTEM
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, (2013/03/26)
Organic compounds showing the ability to inhibit effector toxin secretion or translocation mediated by bacterial type III secretion systems are disclosed. The disclosed type III secretion system inhibitor compounds are useful for combating infections by Gram-negative bacteria such as Salmonella spp., Shigella flexneri, Pseudomonas spp., Yersinia spp., enteropathogenic and enteroinvasive Escherichia coli, and Chlamydia spp. having such type III secretion systems.
Composition and process for promoting the growth of crop plants
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, (2008/06/13)
Compounds of the formula wherein Ar is (substituted) phenyl or naphthyl, X is oxygen, sulfur, SO or SO2, n is 1-3 and R is CN or C(NH2)NOR1, (wherein R1 is preferably hydrogen) are useful as safeners in crop protection.
