Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-10-12
1998-11-10
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514210, 514326, 514422, 514444, 514471, 540480, 540496, 546212, 546213, 546214, 548517, 548527, 548950, H61K 31445, H61K 3155, C07D40706, C07D40904
Patent
active
058344608
DESCRIPTION:
BRIEF SUMMARY
This is a 371 of PCT/JP94/00697, filed Apr. 26, 1994.
TECHNICAL FIELD
This invention relates to a serine derivative which has an anti-PCP (phencyclidine) action.
BACKGROUND ART
It is known that PCP induces mental symptoms which closely resemble various 135, 1081 (1987)!. On the other hand, administration of PCP into animals induces various types of abnormal behavior. Accordingly, a drug which specifically inhibits the PCP-induced abnormal behavior in animals (a drug having anti-PCP action) is considered to be useful as a therapeutic drug for schizophrenia in human.
Dopamine receptor blocking drugs have mainly been used as therapeutic drugs for schizophrenia. These dopamine blocking drugs, however, have problems in that not only their effect against negative symptoms is low but also they cause side effects such as extrapyramidal syndrome.
On the contrary, the specific anti-PCP drug is excellent in that it can improve negative symptoms of schizophrenia, which cannot be cured by the dopamine blocking drugs and that it does not cause side effects which exist in the dopamine blocking drugs.
DISCLOSURE OF THE INVENTION
The inventors of the present invention have conducted intensive studies on the development of a compound having excellent and specific anti-PCP action and, as the result, accomplished the present invention by creating a nitrogen-containing cycloalkyl lower alkyl group-substituted thienyl, furyl or thiazolyl serine derivative, or salts thereof, whose chemical structure is completely different from those of the prior art compounds. Though an unsubstituted thienyl serine derivative (J. Chromatogr., 515, Proc. Int. Congr. Anal. Sci., 1991, Pt. 1), 177-80! and 5-alkylthienyl or 5-phenylhexylthienyl serine derivative (EP-A-446798) are known in the art as thienyl serine derivatives, these reports do not disclose anti-PCP action of the derivatives.
According to the present invention, there is provided a serine derivative represented by the general formula (I) ##STR2## (symbols in the formula represent the following meanings; X: a sulfur atom or an oxygen atom, represents a hydrogen atom, a lower alkyl group or a protecting group for the amino group, or R.sup.1 and R.sup.2 may be combined together to form a four- to nine-membered nitrogen-containing cycloalkyl group, aralkyl group, or a lower alkyl group unsubstituted or substituted with a hydroxyl group, cycloalkyl group unsubstituted or substituted with a lower alkyl group or an aralkyl group or the condensation of a four- to eight-membered nitrogen-containing cycloalkyl group with a benzene ring, and thereof.
In the general formula (I), a serine derivative represented by the following general formula (Ia) or a pharmaceutically acceptable salt thereof is preferable. ##STR3## (symbols in the formula represent the following meanings; X: a sulfur atom or an oxygen atom, group, an acyl group, an aralkyl group, an aralkyloxycarbonyl group or an aralkylaminocarbonyl group, nine-membered nitrogen-containing cycloalkyl group, an aralkyl group or a lower alkyl group unsubstituted or substituted with a hydroxyl group, cycloalkyl group unsubstituted or substituted with a lower alkyl group or an aralkyl group or the condensation of a four- to eight-membered nitrogen-containing cycloalkyl group with a benzene ring, and
The compound of the above general formula (Ia) wherein X is a sulfur atom and Y is CH, i.e., a serine derivative represented by the following general formula (II) or a pharmaceutically acceptable salt thereof is more preferable. ##STR4##
The compound of the above general formula (II) wherein R.sup.2 is a hydrogen atom, B is a saturated or unsaturated four- to ten-membered nitrogen-containing cycloalkyl group unsubstituted or substituted with an aralkyl group and . . . is a single bond, i.e., a serine derivative represented by the following general formula (III) or a pharmaceutically acceptable salt thereof is the most preferable. ##STR5##
The following describes the compounds (I), (Ia), (II) and (III) of the present invention in detail.
Unless
REFERENCES:
patent: 4382929 (1983-05-01), Bradshaw et al.
patent: 5466691 (1995-11-01), Nakao et al.
Sice, "Preparation and Reactions of 2-Methoxythiopene," Journal of American Chemical Society, vol. 75, pp. 3697-3700 (1953).
Yamada et al., "Separation of peptide diastereomers by reversed-phase high-performance liquid chromatography and its application," Journal of Chromatography, vol, 515, pp. 475-482 (1990).
Nakajima et al., "The Utility of 4-(2-Thienyl)Pyridines as a Derivatization Reagent for HPLC and Ce," Analytical Sciences, vol. 7, pp. 177-180 (1991).
Nakao, Chemical Abstract 119:2498252 (1993) for WO 93/03025 (Feb. 18, 1983).
Pfizer, Chemical Abstract 93:220595h for JP 80-55143 (Apr. 22, 1980).
Iwata Masahiro
Kohara Atsuyuki
Koshiya Kazuo
Morita Takuma
Noda Ichio
Raymond Richard L.
Yamanouchi Pharmaceutical Co. Ltd.
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