130477-52-0 Usage
Description
L-655,708 is a pharmaceutical compound that functions as an α5 GABAA receptor inverse agonist. It is designed to modulate the activity of the α5 subunit of the GABAA receptor, which plays a crucial role in various neurological and cognitive processes.
Uses
Used in Pharmaceutical Industry:
L-655,708 is used as a research tool for studying the role of α5 GABAA receptors in various neurological and cognitive disorders. Its ability to inhibit the discriminative stimulus of propofol in a dose-dependent manner makes it a valuable compound for investigating the underlying mechanisms of these conditions and potentially developing novel therapeutic strategies.
Used in Anesthetic Research:
L-655,708 is used as an α5 GABAA receptor inverse agonist to inhibit the discriminative stimulus of propofol, a widely used anesthetic agent. This application helps researchers understand the interaction between propofol and the GABAA receptor, which could lead to the development of more effective and safer anesthetic drugs.
Please note that the provided materials only mention the use of L-655,708 in the context of inhibiting the discriminative stimulus of propofol. If there are other applications or industries where L-655,708 is used, they are not mentioned in the provided materials.
Biological Activity
Potent, selective inverse agonist for the benzodiazepine site of GABA A receptors containing the α 5 subunit (K i = 0.45 nM). Displays 50-100-fold selectivity over GABA A receptors containing α 1, α 2, α 3 or α 6 subunits in combination with β 3 and γ 2. Enhances LTP in? a mouse hippocampal slice model and increases spatial learning, without displaying proconvulsant activity.
Biochem/physiol Actions
L-655,708 is an inverse agonist of the α5 γ-Aminobutyric acid type A (GABAA) receptor. It has an ability to increase cognition in rats.
Check Digit Verification of cas no
The CAS Registry Mumber 130477-52-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,3,0,4,7 and 7 respectively; the second part has 2 digits, 5 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 130477-52:
(8*1)+(7*3)+(6*0)+(5*4)+(4*7)+(3*7)+(2*5)+(1*2)=110
110 % 10 = 0
So 130477-52-0 is a valid CAS Registry Number.
InChI:InChI=1/C18H19N3O4/c1-3-25-18(23)15-16-14-5-4-8-20(14)17(22)12-9-11(24-2)6-7-13(12)21(16)10-19-15/h6-7,9-10,14H,3-5,8H2,1-2H3/t14-/m0/s1
130477-52-0Relevant articles and documents
Optimization of substituted imidazobenzodiazepines as novel asthma treatments
Jahan, Rajwana,Stephen, Michael Rajesh,Forkuo, Gloria S.,Kodali, Revathi,Guthrie, Margaret L.,Nieman, Amanda N.,Yuan, Nina Y.,Zahn, Nicolas M.,Poe, Michael M.,Li, Guanguan,Yu, Olivia B.,Yocum, Gene T.,Emala, Charles W.,Stafford, Douglas C.,Cook, James M.,Arnold, Leggy A.
, p. 550 - 560 (2017)
We describe the synthesis of analogs of XHE-III-74, a selective α4β3γ2 GABAAR ligand, shown to relax airway smooth muscle ex vivo and reduce airway hyperresponsiveness in a murine asthma model. To improve properties of this compound as an asthma therapeutic, a series of analogs with a deuterated methoxy group in place of methoxy group at C-8 position was evaluated for isotope effects in preclinical assays; including microsomal stability, cytotoxicity, and sensorimotor impairment. The deuterated compounds were equally or more metabolically stable than the corresponding non-deuterated analogs and increased sensorimotor impairment was observed for some deuterated compounds. Thioesters were more cytotoxic in comparison to other carboxylic acid derivatives of this compound series. The most promising compound 16 identified from the in vitro screens also strongly inhibited smooth muscle constriction in ex vivo guinea pig tracheal rings. Smooth muscle relaxation, determined by reduction of airway hyperresponsiveness with a murine ovalbumin sensitized and challenged model, showed that 16 was efficacious at low methacholine concentrations. However, this effect was limited due to suboptimal pharmacokinetics of 16. Based on these findings, further analogs of XHE-III-74 will be investigated to improve in vivo metabolic stability while retaining the efficacy at lung tissues involved in asthma pathology.