Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1989-02-03
1991-03-26
Springer, David B.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
548494, C07D20918, A61K 31405
Patent
active
050029630
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION
The present invention relates to novel compounds which are derivatives, in the form of salts, esters and amides, of 3-indolepyruvic acid.
The present invention further relates to the use of 3-indolepyruvic acid, and the above mentioned derivatives thereof, as pharmaceutically active agents for the treatment of disturbances of the central nervous system produced in the brain by the presence of a great amount of superoxide anions or free radicals. Representatives of such disturbances are epilepsy, cerebral ischemia, ictus and Alzheimer's disease.
It has been shown that pharmaceutical administration of the compounds according to the invention produces at the brain level an increase of kynurenic acid, which has been recognised as a natural antagonist of the excitatory aminoacids.
REFERENCES TO THE PRIOR ART
3-indolepyruvic acid is a known compound.
In published European Patent Application No. 106813, corresponding to U.S. Pat. No. 4551471, a process for the enzymatic synthesis of 3-indolepyruvic acid is described, which uses aspartate aminotransferase as an enzyme.
In published European Application No. 0227787 a process for the chemical synthesis of 3-indolepyruvic acid is described, which uses a coupling reaction starting from L-tryptophan.
Moreover, it has been known for several years that tryptophan derivatives can interact in mammals with the receptors of so-called "excitatory aminoacids", namely glutamate, N-methyl-aspartate, ibotenic acid, kainic acid, and so on.
In particular it has been observed that quinolinic acid and kynurenine are powerful agonists of excitatory aminoacids present in the central nervous system of mammals (as an example see: Science 219, 316-8, 1983; Neuropharmacology 23, 333-7, 1984) and they can lead to a rapid neuronal decay similar to that observed in epilepsy and Huntington's Chorea (TIPS 1984, page 215).
The clinical importance of the excitatory aminoacids has become of considerable interest, such as to induce the organization of periodical symposiums for up-dating, such as the one held in London on the 13th and 14th April 1987 ("Excitatory aminoacids in health and disease") and the publication of full monographic editions in scientific magazines (see TINS, Volume 10, No. 7, 1987). According to the most recent views, the inhibitors of excitatory aminoacids can be used for blocking tremor and spasticity, epilepsy, neurodegenerative disorders, cerebral ischemia, psychosis, and the consequences of cerebral ictus (Scrip 1198, 27, 1987).
It has recently been discovered that a further derivative of tryptophan, namely kynurenic acid, is a powerful inhibitor of the excitatory effects manifested by quinolinic acid, N-methyl-D-aspartate and other aminoacids (J. Pharmacol. Exptl. Ther. 236, 293-9, 1986) and it could therefore hinder the neuronal decay in the brain produced by the above mentioned compounds during epileptic attacks, ictus, cerebral ischemia and more generally in neuronal alteration effects occurring during aging.
However, it is not possible to obtain an increase of kynurenic acid at the brain level by means of the administration of kynurenic acid itself, in that the blood-brain barrier prevents the compound from reaching the brain from the outside. Consequently it cannot be usefully administered either orally or via normal injection, to increase the cerebral level of kynurenic acid. It is known, moreover, from the prior art that kynurenic acid is an endogenous compound. It is originated in very small amounts from food tryptophan. However, not even tryptophan can be administered as a drug for this use, in that it is also transformed into kynurenines which have an action which antagonizes that of kynurenic acid.
It has been shown previously (published European Application No. 106813) that 3-indolepyruvic acid is a privileged precursor of cerebral serotonin and, as such, it could be used pharmacologically in all the diseases characterized by a lack of such an endogenous amine.
SUMMARY OF THE INVENTION
It has now been surprisingly found that 3-indolepyruvic
REFERENCES:
Chemical Abstracts, vol. 91:21026g.
Chemical Abstracts, vol. 75:05992w.
De Luca Giovanna
Di Stazio Giovanni
Margonelli Andrea
Materazzi Mario
Politi Vincenzo
LandOfFree
3-indolepyruvic acid derivatives and pharmaceutical use thereof does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 3-indolepyruvic acid derivatives and pharmaceutical use thereof, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 3-indolepyruvic acid derivatives and pharmaceutical use thereof will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-617469