Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-08-03
1996-05-28
Ramsuer, Robert W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
544174, A61K 31535, C07D26530
Patent
active
055211801
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP94/00186 filed Feb. 8, 1994.
TECHNICAL FIELD
This invention relates to a morpholine derivative or a salt thereof having an antidepressive activity and an antianxiety activity.
BACKGROUND ART
Participation of serotonin (hereinafter referred to as 5-HT) in antidepressive action has been reported [Norio Ogawa (ed.), Shinnonoreseputa, Sekai Hoken Tsushinsha (1991, etc.)], and studies have been directed to 5-HT reuptake inhibition or action on 5-HT receptors.
Tricyclic compounds such as Amitriptyline are widely used clinically as antidepressants. Although Amitriptyline exhibits a 5-HT reuptake inhibitory activity or a 5-HT.sub.2 receptor antagonistic activity, it additionally has a noradrenaline reuptake inhibitory activity and an anticholine activity and exhibits non-selective action and is therefore considered to cause side effects upon the cardiovascular system (e.g., palpitation), thirst, urinary retention, etc. Therefore, drugs which selectively inhibit 5-HT reuptake or selectively act on 5-HT.sub.2 receptors are expected to have reduced side effects. Drugs selectively inhibitory on 5-HT reincorporation which have been clinically used include, for example, Fluoxetine. However, it has been reported that Fluoxetine induces anxiety or insomnia during the course of therapy [Physician's Desk Reference, Medical Economics Company, Oradell, N.J. (1990)].
Drugs which selectively antagonize for 5-HT.sub.2 receptors include, for example, Mianserin which is known as an antidepressive.
In the latest various studies, a compound having a selective 5-HT reuptake inhibitory activity together with a selective 5-HT.sub.2 receptor antagonistic activity is eagerly awaited [Cell Biology to Pharmacology and Therapeutics, 488-504 (1990 ), Psychopathology, 22 (suppl. 1 ), 22-36 (1989), J. Clin. Psychiatry, 52, 34-38 (1991), Psychopharmacol. Bull., 26, 168-171 (1990), and Br. J. Pharmacolo., 100, 793-799 (1990)].
Drugs having both of a 5-HT reuptake inhibitory activity and a 5-HT.sub.2 receptor antagonistic activity include, for example, Trazodone. However, the 5-HT reuptake inhibitory activity of Trazodone is very weak, and it was reported that the antidepressive activity and antianxiety activity of Trazodone are based on its antagonism for 5-HT.sub.2 receptors. [Marek G. J., et al., Psychopharmacology, 109, 2-11 (1992)]. Further, in addition to the above two activities Trazodone also exhibits affinity to .alpha..sub.1 receptors and therefore causes sides effects based thereon.
JP-A-46-7333 (the term "JP-A" means an "unexamined published Japanese patent application") discloses 2-[[(4-indanyl)oxy] methyl]morpholine, and JP-A-52-83773 discloses 2-[[(7-indenyl)oxy]methyl]morpholine. However, these compounds have no substituent on the indanyloxy group or indenyloxy group thereof.
DISCLOSURE OF THE INVENTION
The present invention relates to a morpholine derivative which is structurally characterized by its halogen atom on the benzene ring of an indanyloxy group or an indenyloxy group and therefore quite different in chemical structure from the conventional compounds.
The morpholine derivative of the present invention exhibits a selective 5-HT reuptake inhibitory activity and a selective 5-HT.sub.2 receptor antagonistic activity, both the activities produce excellent effects.
An object of the present invention is to provide a novel morpholine derivative represented by the formula (I) shown below or a salt thereof.
Another object of the present invention is to provide a medicine having a selective 5-HT reuptake inhibitory activity together with a selective 5-HT.sub.2 receptor antagonistic activity which comprises as an active ingredient the compound (I) of the present invention or a salt thereof and to provide a pharmaceutical composition comprising the compound (I) of the present invention or a salt thereof and a pharmaceutically acceptable carrier.
The present invention includes in its scope a compound represented by the formula (II) shown below, which is included in the compound (I) of the p
REFERENCES:
patent: 3714161 (1973-01-01), Blakeney et al.
Fujii Mitsuo
Hayashibe Satoshi
Suzuki Takayuki
Tsukamoto Shin-ichi
Yamaguchi Tokio
Ramsuer Robert W.
Yamanouchi Pharmaceutical Co. Ltd.
LandOfFree
Morpholine derivative does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Morpholine derivative, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Morpholine derivative will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-786941