Pyrimidine derivatives and drugs

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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5142222, 5142228, 514269, 544 3, 544 55, 544 59, 544 69, 544295, 544296, 544319, 544326, A61K 31505, C07D40304, C07D40312

Patent

active

055894771

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

This invention relates to pyrimidine derivatives and their pharmacologically acceptable salts represented by the following general formula [I]. ##STR2## wherein A and B are as follows: When A represents ##STR3## B represents methyl, trifluoromethyl, or tert-butyl; When B represents ##STR4## A represents methyl, trifluoromethyl, or tert-butyl. R.sup.1 and R.sup.2 are the same or different and each is a hydrogen atom, a hydroxy group, an alkoxy group, trifluoromethyl or halogen. R.sup.2 represents (1), (2) or (3), represented by the following formulas. ##STR5## wherein Y represents O or NH. ##STR6## wherein R.sup.4 and R.sup.5 represent the following (a) or (b). (a) R.sup.4 and R.sup.5 are the same or different and each is hydrogen or alkyl group. an aryl group or an aralkyl group. ##STR7## wherein Y represents O or NH. m is 2 or 3. R.sup.6 and R.sup.7 are the same or different and each is a hydrogen atom or an alkyl group, or form a 5 to 6 membered cyclic-amino group with the adjacent nitrogen atom. These cyclic-amino groups may include another nitrogen, oxygen or sulfur atom, and moreover, those may be substituted with an aryl group with or without substituent(s), an aralkyl group with or without substituent(s), or an aroyl group with or without substituent(s).
Since the compounds of the present invention have improving effect on learning and memory disorders with low toxicity as described later, those are useful as remedies for dementia etc.


BACKGROUND ART

According with the aging of the population, dementia have been a dominant disease in the medication of the elderly patients. However, the remedies for the treatment of dementia have not been established. Cerebral metabolism enhancers, cerebral blood flow improving agents, tranquilizers. cholinomimetic agents and the like have been tried to use for the treatment. However, the effect of these agents are not reproducible and insufficient. Therefore, better remedies for treatment have been required.
In the dementia of alzheimer type, a type of senile dementia, various nervous systems are damaged. Especially, it has been reported that cholinergic nervous systems, which play important roles in learning and memory functions, are significantly damaged. Therefore, the development of central acethylcholinergic neuron enhancers have been an large stream of development in the improving agents for learning and memory disorders. As for the acethylcholinergic neuron enhancers, precursors (such as choline and lecithin), choline esterase inhibitors or muscarinic agonists have been developed so far. However, they are not satisfactory enough.
On the other hand, various kinds of pyrimidine derivatives have been reported.(for example, CA 93:45871w, 97:158036d, 98:34562y, 100:209733u, 101:110856v, 102:162193s, 104:47176t, 107:236641p, 109:92924z and so forth). It is described in CA 100:209733u that the phleomycin amplifying effect of the compounds which have similar structures to the compounds of the present invention. Also in CA 104:47176t, it is described that the plant's growth regulating effect of the compounds which have similar structures to the compounds of the present invention.
However, up to this point, there have been no literatures describing that the compounds of the present invention and analogous pyrimidine derivatives have improving effects on learning and memory disoders.


DISCLOSURE OF THE INVENTION

The inventors have studied in order to obtain the compounds which are superior to the conventionally known drugs for learning and memory disorders in point of effectiveness, safety and durability.
Accordingly, the object of the present invention has been to obtain new compounds which have improving effect on learning and memory disorders with good selectivity in central nervous system and little side effects and then to provide a good medicine for the treatment of dementia.
The gist of the present invention is in the chemical structure of the compound itself which is represented by a general formula [I]. These are not only new compounds whi

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Thompson et al. New England Journal of Medicine, 323, pp. 445-448, 1990.
Pomora et al. Alan R. Liss, Inc., Alzheimer's Disease and Related Disorders, pp. 1223-1233, 1989.
Gray te al. Trends in Pharmacological Sciences, pp. 85-89, 1989.
Quirion et al. Trends in Pharmacological Sciences, pp. 80-84, 1989.
D. Collerton, "Cholinergic Function and the Intellectual Decline in Alzheimer's Disease", published in Neuroscience, vol. 19, No. 1, pp. 1-28 (1986).
Brown et al. --Chem Abst., 100, No. 28; 2097334, 1984.
Abstract of Japanese 40/15197, 1965.
Brown et al. Aust. J. Chem., 37(11, pp. 155-163 1984.

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