.beta.-hydroxyaspartic acid derivatives

Details .beta.-hydroxyaspartic acid derivatives .beta.-hydroxyaspartic acid derivatives

1997-10-24

2000-11-14

Barts, Samuel

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Ester doai

514547, 514561, 514567, 562444, 562568, 560 88, 560196, 426549, 426611, A61K 31235

Patent

active

061471135

ABSTRACT:
The present invention provides blockers for glutamate transporters. During a series of syntheses searching for glutamate uptake inhibition in Xenopus oocytes injected with bovine glutamate transporter genes (BGLAST), we obtained .beta.-hydroxyaspartic acid derivatives of the following chemical formula (1): ##STR1## wherein R represents an aromatic acyl group which may be substituted on the ring, a straight or branched lower aliphatic acyl group, an aryl group which may be substituted on the ring, an aralkyl group which may be substituted on the ring, or a straight or branched lower alkyl group; and salts thereof. These compounds are blockers of glutamate transporters, which are useful for the understanding of the function of glutamate transporters and show promise for the treatment of various neurodegenerative diseases.

REFERENCES:
patent: 5183590 (1993-02-01), Carter et al.
Chem Abstracts 119:185900, Carter et al, RN=147696-99-9 1991.
Nicholls et al: "The release and uptake of excitatory amino acids", Tips Special Report, 1991, pp. 68-74.
Rothstein, et al: "Decreased Glutamate Transport by the Brain and Spinal Cord in Amyotrophic Lateral Sclerosis", The New England Journal of Medicine, May 28, 1992, vol. 326, No. 22, pp. 1464-1468.
Storck et al: "Structure, expression, and functional analysis of a Na+-dependent glutamate/aspartate transporter from rat brain", Proc.Natl.Acad.Sci.USA, vol. 89, pp 10955-10959, Nov. 1992, Neurobiology.
Arriza et al: "Functional Comparisons of Three Glutamate Transporter Subtypes Cloned from Human Motor Cortex", The Journal of Neuroscience, Sept. 1994, 14 (9), pp 5559-5569.
Fairman et al: "An Excitatory amino-acid transporter with properties of a ligand-gated chloride channel", Nature, vol. 375, Jun. 15, 1995, pp 599-603.
Arriza et al: "Excitatory amino acid transporter 5, a retinal glutamate transporter coupled a chloride conductance", Proc. Natl. Acad. Sci. USA, vol. 94, pp 4155-4160, Apr. 1997, Neurobiology.
Riordan et al: "Some Reactions of DL-trans-4,5-Dicarbomethoxy-2-phenyl-2-oxazoline", J.Org.Chem., vol. 40, No. 22, 1975, pp. 3219-3221 Month Unavailable.
"Functional Comparisons of Three Glutamate Transporter Subtypes Cloned from Human Motor Cortex", Jeffrey L. Arriza, et al., The Journal of Neuroscience, Sept. 1994, pp. 5559-5569.
"New B-Hydroxyaspartate Derivatives Are Competitive Blockers for the Bovine Glutamate/Aspartate Transporter", Bruno Lebrun et al., The Journal of Biological Chemistry, vol. 22, No. 33, Aug. 15, 1997, pp. 20336-20339.
"Some Reactions of DL-trans-4.5-Dicarbomethoxy-2-phenyl-2-oxazoline", James M. Riordan, et al., J. Org. Chem., vol. 40, No. 22, 1975, pp. 3219-3221.

Affiliated with

Also associated with

Rating

.beta.-hydroxyaspartic acid derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with .beta.-hydroxyaspartic acid derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and .beta.-hydroxyaspartic acid derivatives will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2065877