Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1998-05-15
1999-11-23
Richter, Johann
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514641, 514649, 514650, 549 75, 564271, 564272, 564276, 564355, 564360, A61K 31135, A61K 3138, C07D33306
Patent
active
059901519
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP96/01613 filed on Jun. 13, 1996.
1. Technical Field
The present invention relates to optically active, substituted phenylalkylamine derivatives having an antipsychotic action.
2. Background Art
Antipsychotic agents are used for treating not only schizophrenia but also troublesome behaviors in cerebrovascular diseases and senile dementia (aggressive behaviors, mental excitement, poriomania, delirium, etc.).
However, conventional antipsychotic agents cause strong extrapyramidal disorders and thus their use has become a serious problem. In order to solve this problem, recent development of antipsychotic agents has been made by an approach utilizing a mode of action of drugs which is quite different from that of conventional drugs.
One of the thus developed antipsychotic agents is a sigma receptor antagonist. Sigma receptors are classified into sigma 1 receptor and sigma 2 receptor (Trends in Pharmacological Sciences, Vol. 13, pp. 85-86). It has been made clear that pentazocine (Clinical Pharmacology and Therapeutics, Vol. 9, pp. 142-151) and SKF10047 (N-arylnormethazocine) (Advances in Chemistry Series, Vol. 45, pp. 170-176) which develop psychotic symptoms in humans have high affinity for sigma 1 receptor (agonist) (Trends in Pharmacological Sciences, Vol. 13, pp. 85-86). A sigma receptor, particularly, sigma 1 receptor is considered to be a receptor involved in mental aberration such as hallucination symptoms. Compounds having specific affinity for this receptor exhibit an antipsychotic action without causing extrapyramidal disorders.
As a sigma antagonist, Rimcazole is known, for example. However, both its specificity to and affinity for sigma 1 receptor are not sufficient.
DISCLOSURE OF THE INVENTION
It is an object of the present invention to provide novel compounds which have an antipsychotic action without causing extrapyramidal disorders.
As a result of extensive and intensive researches on optically active, substituted phenylalkylamine derivatives, the present inventors have found novel optically active, substituted phenylalkylamine derivatives which have specific and high affinity for sigma 1 receptor. Thus, the present invention has been achieved.
Hereinbelow, the present invention will be described.
The present invention includes the following inventions. represented by Formula [1]: ##STR2## wherein A is a substituted or non-substituted phenyl or thienyl; X.sup.1 is hydrogen, halogen, hydroxyl or a substituted or non-substituted C.sub.1-5 alkoxy; R.sup.1 and R.sup.2 are equally or differently hydrogen, C.sub.1-7 alkyl, C.sub.3-7 alkenyl or C.sub.3-7 alkynyl; R.sup.3 is C.sub.1-10 alkyl, C.sub.2-10 alkenyl or C.sub.2-10 alkynyl; n is an integer from 2 to 5; and m is an integer from 1 to 4, Formula [1]. R.sup.3 is 3-methylbutyl or butyl; X.sup.1 is 4-methoxy; and A-(CH.sub.2)n-O is 3-(2-phenylethoxy) in Formula [1]. of (1).
In the present invention, as the substituted phenyl represented by A, phenyl which is substituted by any one to three substituents selected from halogen, hydroxyl and C.sub.1-5 alkoxy may be used.
In the present invention, the term "halogen" means fluorine, chlorine, bromine or iodine.
The C.sub.1-5 alkoxy is a straight-chain or branched-chain alkoxy such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, t-butoxy, pentoxy, 3-methylbutoxy, etc. These alkoxys may be substituted by, for example, phenyl. As C.sub.1-5 alkoxy substituted by phenyl, benzyloxy, 2-phenylethoxy, 3-phenylpropoxy and the like may be enumerated.
The C.sub.1-7 alkyl represented by R.sup.1 or R.sup.2 is straight-chain, branched-chain or cyclic alkyl, or alkyl substituted by cyclic alkyl. Specific examples include methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, isobutyl, cyclopropylmethyl, pentyl, isoamyl, 3-methylbutyl, cyclobutylmethyl, hexyl, 4-methylpentyl, 2-ethylbutyl, cyclopentylmethyl, heptyl, 5-methylhexyl and cyclohexylmethyl. Preferable are propyl, isopropyl, cyclopropyl, butyl and the like.
The C.sub.3-7 alkenyl represented by R.sup.1 or R.sup.2 i
REFERENCES:
patent: 4329367 (1982-05-01), Francis
patent: 4971995 (1990-11-01), Schoofs et al.
Hatayama, deceased Katsuo
Kawashima Yutaka
Kumagai Toshihito
Miyazawa Tomoki
Nakazato Atsuro
Dolan John F.
Richter Johann
Taisho Pharmaceutical Co. Ltd.
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