Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Patent
1996-03-20
1998-01-06
Shippen, Michael L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
C07C22900
Patent
active
057056870
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The invention relates to the field of medicine, more specifically to the pharmaceutical field, in particular, to a new neurotropic drug which affects the central nervous system and may be used in neurology, psychiatry, including in the treatment of Alzheimer' diseases
BACKGROUND
The invention concerns new derivatives of .gamma.-aminobutyric acid. This acid, known as a preparation under the name of aminalon (gammalon), exhibits neurotropic activity and is used in the practice of medicine. However, it does have a number of disadvantages, such as a low activity level, side effects and a narrow spectrum of action which limits its applications.
Of the various derivatives of the .gamma.-aminobutyric acid currently in use as neurotropic agents, calcium salt of the D-homopantothenic acid, known under the commercial name of "pantogam", is most closely related to the agents of the present invention. (M. D. Mashkovsky, Pharmaceutical Drugs, Moscow, Meditsina, 1986, vol. 1, page 624; Y. Nishizawa, Studies on homopantothenic acid, Medical Journal, Osaka, University, 1984, vol. 35, No. 1,2, pp. 41-50). Pantogam, when compared to aminalon, has superior properties due to better penetration of the hematoencephalitic barrier, which results in higher effectiveness and a wider range of action, at the same time exhibiting sedative and other neurotropic properties. (T. A. Voronina, T. L. Garibova, I. V. Khromova, U. M. Tilekeeva, Dissociation of Anti-amnesic and Antihypoxic Effects of Nootropic and Antihypoxic Drugs, Pharmacology and Toxicology, 1987, No. 3, pp. 21-24).
However, this drug also has several disadvantages. A therapeutic effect is achieved only by administration of a high dose of the drug, up to 3 grams a day. Consequently, it has a very low therapeutic index (3.3), and may sometimes have undesirable side effects, such as depression and myorelaxation.
Furthermore, one of the components of pantogam is the expensive D-pantolactone, which is derived by the separation of the synthetic DL-pantolactone into enantiomers. This multi-stage process involves difficult-to-obtain, toxic and flammable substances and solvents, and results in a considerable amount of waste.
DISCLOSURE OF THE INVENTION
To overcome the disadvantages of the known neurotropic agents, it is the object of this invention to create an effective drug suitable for a broad range of applications, characterized by a low level of toxicity and a high therapeutic index, effective in small doses and with no undesirable side effects.
Another object of this invention is to create the neurotropic agents having the above pharmacological advantages with a simple, safe and inexpensive technological process.
Both of the aforementioned objects are solved by the invention by creating new derivatives of the .gamma.-aminobutyric acid: N-(4-hydroxy-3,3-dimethyl-2-oxo-1-butyryl).gamma.-aminobutyric acid (formula I), ketopatoyl aminobutyrate. ##STR2## and its pharmaceutically acceptable salts.
The new compounds are characterized therein that they include among their constituents, the keto(oxo)pantoic and the .gamma.-aminobutyric acids, which together form an amide bond.
Unexpectedly, the new compounds have demonstrated a therapeutic index two orders higher than that of their analogue, pantogam and the therapeutic index for the subject compounds is over 100. As well, the desired effect was achieved at dosages a whole order lower than those of pantogam. Furthermore, the synthesized compounds have exhibited a broad scope of activity in the central nervous system (sedative as well as anti-amnestic and antihypoxic effects were also observed).
The aforementioned properties are not only characteristic of the ketopantoyl aminobutyrate compound, but also its various salts, in particular, those of calcium and magnesium. Of all the salts derived, however, the best properties were demonstrated by the calcium salt of the synthesized acid.
The second object, that of improving the technological process for preparing the drug of the invention, was solved by substituting
Avakumov Vladimir Mikhailovich
Gunar Vladimir Ivanovich
Karaev Andrei Lvovich
Kozlova Galina Sergeevna
Semina Olga Ivanovna
Nauchno-Proizvodstvennoe Obiedinenie "Vitaminy"
Shippen Michael L.
LandOfFree
Neurotropic drug and method for preparation of same does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Neurotropic drug and method for preparation of same, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Neurotropic drug and method for preparation of same will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2330312