Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Patent
1995-09-11
1998-03-03
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
562499, 562500, 562501, C07C23706, C07C23724, A61K 3116, A61K 31435
Patent
active
057234949
DESCRIPTION:
BRIEF SUMMARY
The subject of the present invention is derivatives of glutamic and aspartic acids which have memory- and learning-enhancing activity and can be represented by the general formulae indicated below: ##STR1## in which r is 1 or 2, R.sub.2 and R.sub.3 are selected independently from H, CH.sub.3, C.sub.2 H.sub.5 and CHO, provided that R.sub.2 and R.sub.3 are not simultaneously CHO, and in which R.sub.1 is selected from: ##STR2## in which R.sub.4 is H or C.sub.1 -C.sub.5 alkyl or alkoxyalkyl, m is a whole number between 0 and 3, L is H or C.sub.1 -C.sub.3 alkyl or alkoxyalky and Ad is adamantyl (1- or 2-yl); ##STR3## in which R.sub.4, m and L have the meanings given above, x and y are selected independently and may have values of between 1 and 4, provided that the ring formed comprises between 5 and 10 carbon atoms; R.sub.5, R.sub.6 and R.sub.7 are selected independently from H and a C.sub.1 -C.sub.4 alkyl or alkoxyalkyl group; ##STR4## in which R.sub.4, R.sub.7, r, x and y have the meanings given above; 4) a dicyclic amine group (orthofused) represented by: ##STR5## in which R.sub.4, R.sub.7, r, x and y have the meanings given above; 5) a dicyclic amino group represented by: ##STR6## in which R.sub.4, R.sub.5, R.sub.6, R.sub.7, L, m, r, x and y have the meanings given above, ##STR7## in which R.sub.5, R.sub.6, R.sub.7, x and y have the meanings given above, 7) an azadicyclic group (orthofused) represented by: ##STR8## in which R.sub.7, r, x, and y have the meanings given above; 8) a dicyclic azaspiro group represented by: ##STR9## in which R.sub.7, r, x and y have the meanings given above, 9) an azadicyclic group represented by: ##STR10## in which R.sub.5, R.sub.6, R.sub.7, r, x and y have the meanings given above; ##STR11## in which R.sub.7, x and y have the meanings given above and T is sulphur, oxygen or N-R.sub.9, where R.sub.9 may be selected from H, C.sub.1 -C.sub.3 alkyl or aryl, unsubstituted or mono- or di-substituted by groups selected from F, Cl, Br, CF.sub.3, NO.sub.2, NH.sub.2, CN, OCH.sub.3, and C.sub.1 -C.sub.3 alkyl; ##STR12## in which R.sub.4 has the meaning given above and R.sub.9 is a linear or branched alkyl or alkoxyalkyl group containing from 3 to 12 carbon atoms. The stereochemistry of the compounds claimed at the chiral centre marked with an asterisk in formulae (I and II) may be racetalc (D, L) or, preferably, L (laevo, sinister).
The compounds of the invention have been found to possess a considerable ability to facilitate learning and to enhance the memory of the various species studied in various experimental models in vivo.
These effects have been shown both in experimental situations in which the "basal" performance was to be increased, such as, for example, in passive-avoidance and active avoidance models in the rat, and in models in which cognitive performance was disturbed, for example, with the use of scopolamine, a drug with central anticholinergic activity, which can bring about an amnesic effect by deactivating the cholinergic neuron net or, alternatively, by inducing amnesia by cerebral electric shock.
It may be suggested that the memory- and learning-enhancing activity of the compounds of the invention may be at least partly correlated with the ability, shown in binding experiments in vitro, to interact with the receptors of the excitor amino-acids of the central nervous system (the CNS), such as the L-glutamate system.
Some of the compounds of the invention have also been found to possess considerable antidepressant activity according to an experimental model in the mouse, which is proposed as a model for evaluating the antidepressant activity of a drug.
As already mentioned, the aforesaid compounds can thus be used with advantage in the treatment and prevention of various diseases linked with deterioration or malfunctioning of the cognitive abilities such as, for example, disorders of mental performance due to mental fatigue, organic and senile cognitive deterioration, Alzheimer's disease, behavioural disorders and depressive syndromes.
The method of preparing the deriv
REFERENCES:
Francesco Makovec et al, Structure--Antigastrin Activity Relationships of New (R)-4-Benzamido-5-oxopentanoic Acid Derivatives, J. Med. Chem. 1992, 35, 28-38.
Makovec Francesco
Peris Walter
Rovati Lucio C.
Rovati Luigi A.
Kifle Bruck
Rotta Research Laboratorium S.p.A.
Shah Mukund J.
LandOfFree
Derivatives of glutamic and aspartic acids, a method of preparin does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Derivatives of glutamic and aspartic acids, a method of preparin, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Derivatives of glutamic and aspartic acids, a method of preparin will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2248067