130477-52-0

Basic information

• Product Name: L-655,708
• Synonyms: ETHYL (S)-11,12,13,13A-TETRAHYDRO-7-METHOXY-9-OXO-9H-IMIDAZO[1,5-A]PYRROLO[2,1-C][1,4]BENZODIAZEPINE-1-CARBOXYLATE;L-655,708;11,12,13,13A-TETRAHYDRO-7-METHOXY-9-OXO-9H-IMIDAZO[1,5-A]PYRROLO[2,1-C][1,4]BENZODIAZEPINE-1-CARBOXYLIC ACID, ETHYL ESTER;11,12,13,13a-Tetrahydro-7-methoxy-9-oxo-9H-imidazo[1.5-a]pyrrolo[2.1-c][1.4]benzodiazepine-1-carboxylicacidethylester;Ethyl (S)-11,12,13,13a-Tetrahydro-7-methoxy-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate;MSD;9H-IMidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylic acid, 11,12,13,13a-tetrahydro-7-Methoxy-9-oxo-, ethyl ester, (13aS)- (011-14426_500Mg);9H-IMidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylic acid, 11,12,13,13a-tetrahydro-7-Methoxy-9-oxo-, ethyl ester, (13aS)-
• CAS NO: 130477-52-0
• Molecular Formula: C₁₈H₁₉N₃O₄
• Molecular Weight: 341.36
• Product Categories: GABA/Glycine receptor
• Mol File: 130477-52-0.mol
• Article Data: 2

Chemical Properties

• Melting Point: 175-176 °C
• Boiling Point: 584.4 °C at 760 mmHg
• Flash Point: 307.2 °C
• Appearance: /powder
• Density: 1.42 g/cm³
• Vapor Pressure: 1.21E-13mmHg at 25°C
• Refractive Index: 1.675
• Storage Temp.: Desiccate at +4°C
• Solubility: DMSO: 6 mg/mL
• PKA: 1.49±0.20(Predicted)
• CAS DataBase Reference: L-655,708(CAS DataBase Reference)
• NIST Chemistry Reference: L-655,708(130477-52-0)
• EPA Substance Registry System: L-655,708(130477-52-0)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 130477-52-0(Hazardous Substances Data)

Usage

Uses

L-655,708 has been used as an α5 GABAA receptor inverse agonist to inhibit the discriminative stimulus of propofol in a dose-dependent manner.

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.

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

Upstream product

• 2999-46-4 Ethyl isocyanoacetate 
• 130477-46-2 (11aS)-7-methoxy-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5,11-dione 
• 1882-69-5 5-methoxy-2-nitro-benzoic acid 
• 6705-03-9 2-Amino-5-methoxybenzoic acid 
• 37795-77-0 6-methoxy-2H-3,1-benzoxazine-2,4(1H)-dione 

Relevant articles and documents

Optimization of substituted imidazobenzodiazepines as novel asthma treatments

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.