1-amino-5-halogenouracils, process for their preparation, and ce

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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544313, 544311, A61K 31505, C07D23902

Patent

active

052525767

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to a central nervous system depressant containing a 1-amino-5-halogenouracil as an active ingredient, a novel 1-amino-5-halogenouracil useful as a central nervous system depressant, and a novel process for preparing the 1-amino-5-halogenouracil.


BACKGROUND ART

Stress on human body tends to increase with the complication of social environment, and thus an increased number of patients complain of symptoms such as sleep duration disorder, insomnia and the like, which are considered to be induced by stress.
Although the physiological phenomenon named sleep is very complicated and its mechanism has not been elucidated in detail, several nucleic acid-related compounds which affect sleep have been reported. Such compounds include the following:
(1) Uridine
Sleep-promoting effect [see Biomed. Res., 4, 223 (1983); Neurosci. Res., 1, 243 (1984); Proc. Natl. Acad. Sci. U.S.A., 81, 6240 (1984); Neuroscience Letters, 49, 207 (1984)];
(2) Uracil
Hexobarbital induced sleep potentiating effect [see J. Am. Pharm. Assoc., 44, 56 (1955); ibid., 44, 550 (1955)];
(3) N.sup.3 -Benzyluridine and its derivatives
Hypnotic effect and/or pentobarbital induced sleep potentiating effect [see Chem. Pharm. Bull., 33, 4088 (1985); Japanese Patent Laid-Open Publication No. 207218/1987];
(4) N-Allyl or N-benzyl substituted derivatives of uracil, thymine or 6-methyluracil
Hypnotic effect and/or pentobarbital induced sleep potentiating effect [see Chem. Pharm. Bull., 35, 4982 (1987); Abstract of the Proceedings of the 108th Annual Meeting of Pharmaceutical Society of Japan, page 708 (1988)].
It has been also reported that the N-allyl substituted derivative of uracil (N.sup.1,N.sup.3 -diallyl uracil) and uridine have anticonvulsive effect [see Brain Res., 55, 291 (1973); Chem. Pharm. Bull., 35, 4928 (1987)].
However, these conventional compounds (i) have no hypnotic effect though they exhibit sleep-promoting effect (uridine and uracil), and (ii) must be administered in large doses (320-752 mg/kg) to induce sleep by intraperitoneal injection, and thus they do not always have satisfactory effects.
An object of the present invention is to provide a central nervous system depressant which comprises as an active ingredient a compound exhibiting more potent central nervous system depressant effects such as hypnotic effect, sleep-promoting effect, anticonvulsive effect and the like than the conventional compounds.


DISCLOSURE OF THE INVENTION

We have conducted extensive research in order to discover a compound which has central nervous system sedative effects. As a result, we have found that 1-amino-5-halogenouracil has excellent central nervous system sedative effects.
While 1-amino-5-fluorouracil has hitherto been known as only one 1-amino-5-halogenouracil, it has not been reported that the compound has central nervous system sedative effects [see Sci. Pharm., 52, 46 (1984)].
An object of the present invention is to provide a central nervous system depressant which comprises a 1-amino-5-halogenouracil represented by the formula: ##STR4## wherein X represents a halogen atom, or a pharmaceutically acceptable salt thereof as an active ingredient.
Another object of the present invention is to provide a novel 1-amino-5-halogenouracil represented by the formula: ##STR5## wherein X' represents chlorine, bromine or iodine, or a salt thereof.
A further object of the present invention is to provide a process for preparing a 1-amino-5-halogenouracil represented by the formula [I] shown above which comprises reacting a pyrimidine derivative represented by the formula: ##STR6## wherein X has the same meaning as defined above and R represents a protective group, with an aminating agent to aminate the 1-position of the pyrimidine derivative, and removing the protective groups.


BEST MODE FOR CARRYING OUT THE INVENTION

The present invention will now be explained in detail below.
The 1-amino-5-halogenouracil which is an active ingredient of the central nervous system depressant of the present invention is the c

REFERENCES:
patent: 4395406 (1983-07-01), Gacek et al.
patent: 4396623 (1983-08-01), Shealy et al.
patent: 4415573 (1983-11-01), Ochi et al.
Yamamoto et al, Chem Pham. Bull. 33 (9) 4088-4090 (1985).
Shimizu et al, Chem. Pharm. Bull, 35 (12) 4981-4984 (1987).
Tateoka et al, Chem. Pharm Bull 35 (12) 4928-4934 (1987).
Inoue et al, Proc. Natl. Acad. Sci. USA vol. 81, 6240-6244 (1984).
Masahiro Imaizumi et al, Chem. Pharm. Bull 40 (7) 1808-1813 (1992).
Nakamizo et al, Chem. Abst. 107-134623s (1987).

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