Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1993-04-16
1994-06-07
Rotman, Alan L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C07D40312, C07D40112
Patent
active
053190858
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a quinoline derivative having a serotonin-3 receptor (hereafter referred to as 5HT.sub.3) antagonizing activity.
BACKGROUND ART
It is known that 5HT.sub.3 antagonists exhibit an antiemetic activity, an antianxious activity, a suppressing activity of mental disorders, etc. [Trends in Pharmacological Sciences, 8, 501 (1987)]. 5HT.sub.3 antagonists are effective against carcinostatic agent-induced vomiting, which has not been cured by dopamine antagonists. The 5HT.sub.3 antagonists are thus expected to be antiemetics of new type [Br. J. Cancer, 56, 159 (1987)].
It is disclosed in Japanese Published Unexamined Patent Application No. 72886/85 (U.S. Pat. No. 4,797,406) that quinoline derivatives represented by formula (A): ##STR2## wherein R.sup.4 represents hydrogen, hydroxy or a lower alkoxy (C.sub.1 to C.sub.4); X.sup.1 represents --O-- or --NH--; and p represents 0 or 1, have a 5HT.sub.3 antagonizing activity and an antiarrhythmic activity. That publication merely discloses a compound having azabicyclononane ring (p=1) in formula (A) (hereafter referred to as Compound C): ##STR3## but is silent about any specific compounds having azabicyclooctane ring (p=0). It is also disclosed in Japanese Published Unexamined Patent Application No. 41429/88 (GB-A-2193633) that the compounds represented by formula (A) are effective against vomiting caused by carcinostatic agents such as Cisplatin. Further, Japanese Published Unexamined Patent Application No. 203365/89 (EP-B-0323077) describes quinoline derivatives represented by formula (B): ##STR4## wherein X.sup.2 represents a single bond or CO, and R.sup.4, X.sup.1 and p have the same meanings as described above, but no specific compounds having formula (B) are disclosed therein.
DISCLOSURE OF THE INVENTION
The present invention relates to quinoline derivatives represented by formula (I): ##STR5## wherein A-B-D represents --C(COO--Y).dbd.CH--C(OR).dbd.[hereafter referred to as formula(.alpha.)](wherein Y represents 8-methyl-8-azabicyclo[3.2.1]oct-3-yl group and R represents methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl or hexyl) or --C(OH).dbd.C(COX--Y)--CH.dbd.[hereafter referred to as formula (.beta.)](wherein X represents --O-- or --NH--; and Y has the same meaning as described above), or a pharmaceutically acceptable salt thereof.
Hereafter the compounds represented by formula (I) are referred to as Compound (I). With respect to the compounds of other formula numbering, the same shall apply.
As the pharmaceutically acceptable salt of Compound (I), mention may be made of inorganic acid salts such as hydrochlorides, sulfates, phosphates, etc.; organic acid salts such as acetates, maleates, fumarates, tartarates, citrates, etc.
The processes for preparing Compound (I) are described below.
In the following processes, where the defined group changes under conditions given or is inappropriate for practicing the processes, the group may be treated in a manner conventional to organic synthetic chemistry, for example, protection of a functional group, removal of the protection, etc. so that the processes may be easily carried out.
Process 1
Compound (Ia) which is Compound (I) where A-B-D means formula (.alpha.), may be obtained according to the following reaction equation in the presence of a base: ##STR6## wherein R and Y have the same meanings as described above and L represents a leaving group.
Herein, the leaving group denoted by L refers to halogen such as chlorine, bromine, iodine, etc.; alkoxy such as methoxy, ethoxy, etc.; aryloxy such as phenoxy, p-nitrophenoxy etc.; alkoxycarbonyl such as ethoxycarbonyl, isobutyloxycarbonyl, etc.; 1-imidazolyl group; 1-pyrrolidyl group, etc.
Compound (II) can be prepared by the method of Reference Examples as described hereafter, or according to a similar manner thereto. Compound (II) is commercially available, as the case may be. Compound (III) is a known compound which can be prepared by the method as described in Japanese Published Unexamined Patent Applicatio
REFERENCES:
patent: 4797406 (1989-01-01), Richardson et al.
Hayashi Hiroaki
Ichikawa Shunji
Ishii Akio
Kuroda Takeshi
Miki Ichiro
Kyowa Hakko Kogyo Co. Ltd.
Rotman Alan L.
LandOfFree
Quinoline derivative having serotonin-3 receptor antagonizing ac does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Quinoline derivative having serotonin-3 receptor antagonizing ac, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Quinoline derivative having serotonin-3 receptor antagonizing ac will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-793732