Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Patent
1996-07-30
1997-04-15
Kumar, Shailendra
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
564163, C07C23358
Patent
active
056211422
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP95/00254 filed Feb. 22, 1995.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a novel aminoalkylcyclopropane derivative having an antagonistic activity with respect to N-methyl-D-aspartic acid (hereinbelow, referred to as "NMDA") receptor. More particularly, the present invention is concerned with a novel optically active aminoalkylcyclopropane derivative, a racemic modification thereof, or a pharmaceutically acceptable acid addition salt of the optically active aminoalkylcyclopropane derivative or racemic modification thereof, which has remarkably high antagonistic activity with respect to NMDA receptor, as compared to known aminomethylcyclopropane derivatives and is useful as a preventive agent for cerebral infarction and a protective agent against ischemic diseases.
2. Discussion of Related Art
It has been known that 1-phenyl-2-aminomethylcyclopropane derivatives, such as 1-phenyl-1-diethylaminocarbonyl-2-aminomethyl-cyclopropane hydrochloride (common name: Milnacipran) [hereinafter, referred to as "compound (A)"], represented by the following formula (A): ##STR2## are useful for treating central nervous system neuropathy, and especially effective for treating neurotic depression and psychogenic neurosis (Examined Japanese Patent Application Publication No. 63-23186).
It has also been known that the above-mentioned compound (A) has an activity to inhibit the synaptosomal uptake of norepipephrine and 5-HT, which activity is known as anti-depression activity (Neuropharmacology, Vol. 24, No. 12, 1211-1219, 1985). It has also been known that the above-mentioned 1-phenyl-2-aminomethyl-cyclopropane derivative has an antagonistic activity with respect to NMDA receptor and is useful as a cell protective agent against ischemic brain cell damage (Unexamined Japanese Patent Application Laid-Open Specification No. 3-56415).
In the development of pharmaceutical products, it has been an important task to develop a compound having high antagonistic activity with respect to NMDA receptor, as compared to known compounds.
SUMMARY OF THE INVENTION
In order to solve the above-mentioned problem, the present inventors have made extensive and intensive studies on the steric structure characteristics of a cyclopropane ring. As a result, they have unexpectedly found that, when a specific organic group is introduced to the 2'-position of the cyclopropane ring of the known compound (A) mentioned above, the resultant new optically active compound, a racemic modification thereof, and a pharmaceutically acceptable acid addition salt of the optically active compound and racemic modification thereof, exhibit extremely high antagonistic activity with respect to NMDA receptor, as compared to known compounds. The present invention has been completed, based on this novel finding.
Accordingly, it is an object of the present invention to provide a novel compound having high antagonistic activity with respect to NMDA receptor, as compared to known compounds.
DETAILED DESCRIPTION OF THE INVENTION
According to the present invention, there is provided an optically active compound represented by formula (1), a racemic modification thereof, or a pharmaceutically acceptable acid addition salt of the optically active compound or racemic modification thereof: ##STR3## wherein R is a straight chain or branched C.sub.1 -C.sub.5 aliphatic group which is saturated or unsaturated, or a phenyl group which is unsubstituted or substituted with 1 to 3 substituents which are each independently selected from the group consisting of a halogen atom, a C.sub.1 -C.sub.4 alkyl group, a nitro group, an amino group, a hydroxyl group and a C.sub.1 -C.sub.4 alkoxy group; and mark * indicates an asymmetric carbon atom.
The respective meanings of the abbreviations used in the present specification are as follows:
In the present specification, a positional numbers in a compound are in accordance with the positional numbers indicated in formula (1).
In the above-mentioned formula (1), R is a
REFERENCES:
patent: 4478836 (1984-10-01), Mouzin et al.
"Biochemical Profile of Midalcipran (F 2207), 1-Phenyl-1-Diethyl-Aminocarbonyl-2-Aminomethyl-Cyclopropane (Z) Hydrochloride, a Potential Fourth Generation Antidepressant Drug", Neuropharmacology, vol. 24, No. 12, 1985, pp. 1211-1219.
Mochizuki Daisuke
Shuto Satoshi
Asahi Kasei Kogyo Kabushiki Kaisha
Kumar Shailendra
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