Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1988-12-06
1990-09-11
Friedman, Stanley J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
A61K 31535
Patent
active
049563645
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a nootropic agent comprising a histidylprolinamide derivative as a main ingredient.
The histidylprolinamide derivative in accordance with the present invention can be represented by the following general formula [I]. ##STR2## where in R represents a lower alkyl group.
BACKGROUND OF THE INVENTION
As the population of aged persons increases, sinile dementia has been a serious problem but its therapy has not yet been established. Drug therapy by administration of a cerebral metabolism activator, a cerebral blood flow improving agent, a tranquillizer, a cholinergic agent, etc. has been attempted heretofore but its effect is not satisfactory and a new therapeutic agent has been desired in this field.
Recently, some compounds such as Aniracetam, Pramiracetam, etc. have been developed as nootropic agents but are not yet satisfactory in terms of their effects.
In Published Unexamined Japanese Patent Application No. 52-125166 etc.,TRH (Thyrotropin releasing hormone) compounds are disclosed and studies on nootropic activity of TRH have been advanced in these years.
It has been considered that TRH is principally a hormone for regulating release of thyrotropin (TSH) in pituitary gland of mammals. According to recent studies, however, it has been made clear that TRH not only releases TSH but . also widely exists in the central nervous system and possesses various activities [Ann. Rev. Pharmacol. Toxicol., 26, 311-322 (1986)].
It was known that TRH showed various useful activities and could be a useful medicine as a nootropic agent. It was also known that TRH was relatively rapidly decomposed in vivo and its penetration into the brain was not so good. Besides, it can be said that the activity itself of TRH is not so potent as expected and it has been demanded to develop derivatives having a more potent activity.
In addition, the effect of TRH cannot be expected by oral administration in its nature, which is a serious defect as a drug.
On the other hand, investigations have been made on histidylprolinamide derivatives including the compounds of the present invention which are known compounds as substances having an effective pharmacological activity; for example, these derivatives have been attempted to utilize as drugs for treating traumatic neurosis (Published Unexamined Japanese Patent Application No. 61-172828). However, no attempt has been made to investigate the compounds of the present invention by specifying them to specific pharmacological activity, thereby leading to materialization of some new drugs.
DISCLOSURE OF THE INVENTION
In view of the foregoing actual situation, the present inventors have made extensive investigations on the limited compounds of the present invention. As a result, it has been confirmed that the compounds represented by the general formula [I]described above have much more excellent nootropic activity on mammals than TRH and the present invention has come to be accomplished.
As described above, the compounds of the present invention are known and it has been made clear that the compounds have pharmacological activities other than the nootropic activity. However, as will be later described in detail, such an excellent nootropic activity in accordance with the present invention that the activity is sufficiently exhibited even by oral administration has been found by the present inventors for the first time and this is an important feature of the present invention.
The compounds of the present invention can be represented by the general formula [I]described above. As R in [I], mention may be made of a lower alkyl group such as methyl, ethyl, propyl, etc.
Examples of the compounds of the present invention include the following compounds.
Hereafter pharmacological activities and toxicity of the compounds of the present invention will be described below in detail. In the following experiments, (3R,6R)-6-methyl-5-oxo-3-thiomorpholinylcarbonyl-L-histidyl-L-prolinamide was used as the compound of the present invention.
(1) Effects
REFERENCES:
Chem. Abst. 101-123206h (1984).
Kimura Kiyoshi
Nakagawa Yutaka
Ogasawara Takashi
Ukai Yojiro
Friedman Stanley J.
Nippon Shinyaku Co. Ltd.
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