139051-78-8

Basic information

• Product Name: L-689,560
• Synonyms: L-689,560;TRANS-2-CARBOXY-5,7-DICHLORO-4-PHENYLAMINOCARBONYLAMINO-1,2,3,4-TETRAHYDROQUINOLINE;4-trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4-tetrahydroquinoline
• CAS NO: 139051-78-8
• Molecular Formula: C17H15Cl2N3O3
• Molecular Weight: 380.23
• Mol File: 139051-78-8.mol
• Article Data: 4

Chemical Properties

• Melting Point: 172-173°C
• Boiling Point: 549.1°C at 760 mmHg
• Flash Point: 285.9°C
• Appearance: /
• Density: 1.51g/cm³
• Vapor Pressure: 6.81E-13mmHg at 25°C
• Refractive Index: 1.683
• Storage Temp.: Store at RT
• Solubility: <9.51mg/ml in DMSO; <38.02mg/ml in ethanol
• CAS DataBase Reference: L-689,560(CAS DataBase Reference)
• NIST Chemistry Reference: L-689,560(139051-78-8)
• EPA Substance Registry System: L-689,560(139051-78-8)

Safety Data

• Hazardous Substances Data: 139051-78-8(Hazardous Substances Data)

Usage

Uses

L-689,560 is a potent antagonist at the glycine-NMDA receptor site.

Biological Activity

Very potent antagonist at the glycine-NMDA site. Also available as part of the NMDA Receptor - Glycine Site Tocriset? .

in vitro

l-689560 is described as one of the most potent nmda antagonists and [4'-3h]-l-689560 has been thought to be a highly specific radioligand for the glycine site. in consistent with the 5,7-disubstituted kynurenates, the tetrahydroquinolines are selective antagonists of glycine site nmda, l-689560 exhibiting at least 3 orders of magnitude selectivity versus the glutamate site [1].

in vivo

mdl100748 with an ed50 of 83 mg kg-1 can prevent audiogenic seizures in susceptible mice after systemic injection. as a standard l689560, its subsequent analogues have been compared; the displacement of [3h] l689560 has often been used to displace that of [3h] glycine as an alternative assay. l701252, a quinones (the retention of a keto grouping at position 3), has been against l689560 binding (ic50 of 420 nm) and against seizures (ed50 of 4.1 mg kg-1) in dba/2 mice. a group of sulfonamide analogues of kynurenic acid are also in active among the 2-quinolone series. those of a series of 3,4-dihydroquinolones and tetrahydroquinolines with a nitrosubstituent at 3-position were selective antagonists at the nmda receptor glycine site if they bore a bulky grouping in the position 4. the compound with no substitution at position 4 was proved to be one of the most effective broad-spectrum antagonists against nmda and ampa receptors [2].

references

[1]. leeson pd, carling rw, moore kw, moseley am, smith jd, stevenson g, chan t, baker r, foster ac, grimwood s, et al. 4-amido-2-carboxytetrahydroquinolines. structure-activity relationships for antagonism at the glycine site of the nmda receptor. j med chem. 1992 may 29;35 (11): 1954-68.[2]. stone tw. development and therapeutic potential of kynurenic acid and kynurenine derivatives for neuroprotection. trends pharmacol sci. 2000 apr; 21(4):149-54.

InChI:InChI=1/C17H15Cl2N3O3/c18-9-6-11(19)15-12(7-9)21-14(16(23)24)8-13(15)22-17(25)20-10-4-2-1-3-5-10/h1-7,13-14,21H,8H2,(H,23,24)(H2,20,22,25)/t13-,14+/m0/s1

Upstream product

• 103-71-9 phenyl isocyanate 
• 356042-23-4 trans-5,7-dichloro-4-[[(phenylamino)carbonyl]amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid methyl ester 
• 132689-84-0 5,7-Dichloro-4-[(E)-hydroxyimino]-1,2,3,4-tetrahydro-quinoline-2-carboxylic acid methyl ester 
• 132688-39-2 2-carbetoxy-5,7-dichloro-4-oxo-1,2,3,4-tetrahydroquinoline 

Relevant articles and documents

Catalytic enantioselective reissert-type reaction: Development and application to the synthesis of a potent NMDA receptor antagonist (-)-L-689,560 using a solid-supported catalyst

Full details of the first catalytic enantioselective Reissert-type reaction are described. Utilizing the Lewis acid-Lewis base bifunctional catalyst 5 or 6 (9 mol %), the Reissert products were obtained in 57 to 99% yield with 54 to 96% ee. Electron-rich

4-Amido-2-carboxytetrahydroquinolines. Structure-Activity Relationships for Antagonism at the Glycine Site of the NMDA Receptor

trans-2-Carboxy-5,7-dichloro-4-amidotetrahydroquinolines, evolved from the lead 5,7-dichlorokynurenic acid, have been synthesized and tested for in vitro antagonist activity at the glycine site on the N-methyl-D-aspartate (NMDA) receptor.Optimization of the 4-substituent has provided antagonists having nanomolar affinity, including the urea trans-2-carboxy-5,7-dichloro-4-amino>-1,2,3,4-tetrahydroquinoline (35; IC50 = 7.4 nM vs glycine binding; Kb = 130 nM for block of NMDA responses in the rat cortical slice), which is one of the most poten t NMDA antagonists yet found.The absolute stereochemical requirements for binding were found to be 2S,4R, showing that, in common with other glycine-site NMDA receptor ligands, the unnatural configuration at the α-amino acid center is required.The preferred conformation of the trans-2,4-disubstituted tetrahydroquinoline system, as shown by X-ray crystallography and 1H NMR studies, places the 2-carboxyl pseudoequatorial and the 4-substituent pseudoaxial.Modifications of the 4-amide show that bulky substituents are tolerated and reveal the critical importance for activity of correct positioning of the carbonyl group.The high affinity of trans-2-carboxy-5,7-dichloro-4--1,2,3,4-tetrahydroquinoline (55; IC50 = 6 nM) suggests that the Z,Z-conformer of the phenyl urea moiety in 35 is recognized by the receptor.Molecular modeling studies show that the 4-carbonyl groups of the kynurenic acids, the tetrahydroquinolines, and related antagonists based on N-(chlorophenyl)glycine, can interact with a single putative H-bond donor on the receptor.The results allow the establishment of a three-dimensional pharma cophore of the glycine receptor antagonist site, incorporating a newly defined bulk tolerance/hydrophobic region.