Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1988-01-11
1990-12-04
Lee, Lester L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 18, 530331, 562565, A61K 3702, C07C 506
Patent
active
049754181
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel therapeutically active pseudo-peptides useful particularly in the treatment of disorders of the central nervous system such as epilepsy and failures of memory associated with certain degenerative diseases.
The importance of chemical mediators in disorders of the central nervous system (CNS) is known.
Among the latter a distinction is made between inhibitory neurotransmitters such as GABA (gamma-amino-butyric acid) and serotonin, and excitatory neurotransmitters such as histamine, dopamine and glutamic acid.
These latter are more particularly concerned by the present invention, especially the glutamatergic system which acts at different levels of the brain and very probably plays an important role in the mechanisms implicated in the retention of memory (BLISS, DOLPHIN, 1982; ECCLES, 1983; COLLINGRIDE, 1985).
As a matter of fact, the present invention relates to the agonist or antagonist properties of novel pseudo-peptides on neurotransmission, particularly at the level of the glutamatergic system.
Involved are novel pseudo-peptides comprising at least the sequence of .gamma.-glutamyl-aspartic acid as well as derivatives of these pseudo-peptides. Among these pseudo-peptides mention should be made of the acid itself as well as the tripeptides corresponding to an additional amino acid linked to the C-terminal end. The derivatives in question are essentially salts, esters and amides, quaternary amine derivatives as well as cyclic derivatives with pharmaceutically acceptable acidic and basic substances and alcohols.
Preferably, according to the invention, this novel pseudo-peptide is N-.gamma.-glutamyl-aspartic acid itself or one of its derivatives. These substances may exist in any isomeric form, namely they may be in the form of N-.gamma.-L-glutamyl-L-aspartic acid, N-.gamma.-L-glutamyl-D-aspartic acid, N-.gamma.-D-glutamyl-L-aspartic acid or N-.gamma.-D-glutamyl-D-aspartic acid.
A very especially preferred substance according to the present invention is N-.gamma.-L-glutamyl-L-aspartate, the formula of which is the following: ##STR1##
Interesting results have also been obtained with the N-.gamma.-D-glutamyl-D-aspartic acid form.
Another particularly useful pseudo-peptide according to the invention is N-.gamma.-glutamyl-aspartyl-aspartic acid and its derivatives, substances in which each of the amino acids may exist in the right-handed (R, in accordance with the international nomenclature) or the left-handed form (S).
The preferred N-.gamma.-glutamyl-aspartyl-aspartic acid according to the invention is that in which each of the amino acids is present in the left-handed form (S).
The synthesis of the pseudo-peptides according to the present invention can be carried out by the methods known to one skilled in the art of peptide synthesis.
Thus, the coupling of protected glutamic acid, the acidic function being activated if necessary, with protected aspartic acid can be carried out in the presence of a coupling agent such as N,N'-dicyclohexylcarbodiimide.
Similarly, in order to prepare N-.gamma.-glutamyl-aspartyl-aspartic acid, one may start from the compound previously obtained by protecting or activating the appropriate functions and by coupling it to also protected aspartic acid.
These syntheses can be carried out in a solid phase or in an organic phase.
The final step in both of these procedures consists in removing the protecting group(s) by an appropriate technique in order to give rise to N-.gamma.-glutamyl-aspartic acid and N-.gamma.-glutamyl-aspartyl-aspartic acid, respectively, or their derivatives.
The pseudo-peptides according to the present invention are particularly useful for the preparation of a pharmaceutical composition.
This is the reason why the present invention relates to pharmaceutical compositions comprising, as active ingredient, at least one pseudo-peptide according to the invention. These pharmaceutical compositions are useful for the treatment of various diseases affecting the central nervous system, particularly epilepsy and memory disorders.
Durin
REFERENCES:
patent: 2500019 (1950-03-01), Bersworth
patent: 4161522 (1979-07-01), Hamburger
patent: 4585757 (1986-04-01), Pang et al.
patent: 4761495 (1988-08-01), Wirth et al.
Utsumi, Chemical Abstracts (1963) 59:3032a.
Cheung et al., Chemical Abstracts (1979) 91:118993h.
Anderson et al., Chemical Abstracts (1986) 105:127416g.
Rodin et al., Chemical Abstracts (1973) 78:136706c.
CA vol. 77 (1972):85649f Fowden.
CA vol. 80 (1974):93155u Kasai et al.
CA vol. 82 (1975):121068e Kasai et al.
CA vol. 83 (1975):175494e Kasai et al.
CA vol. 94 (1981):188659q Kasai et al. (Takanori).
CA vol. 104 (1986):203870x Kasai et al.
Boulanger Yves L. J.
De Barry Jean
Schmitz-Bourgeois Monique
Ungerer Arielle
Centre National de la Recherche Scientific (CNRS)
Lee Lester L.
Neeley Richard L.
Rowland Bertram I.
LandOfFree
Therapeutically active compositions of pseudo-peptide of glutamy does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Therapeutically active compositions of pseudo-peptide of glutamy, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Therapeutically active compositions of pseudo-peptide of glutamy will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-883447