Quinoline derivatives as bradykinin agonists

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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Details

546153, C07D40112, C07D40114, A61K 31395

Patent

active

060158182

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/JP97/00233 filed on Jan. 31, 1997.
1. Technical Field
This invention relates to new heterocyclic compounds and pharmaceutically acceptable salts thereof.
More particularly, it relates to new heterocyclic compounds and pharmaceutically acceptable salts thereof which have activities as bradykinin agonists, to processes for preparation thereof, to a pharmaceutical composition comprising the same, and to methods of using the same for the therapeutic purpose in human being or animals.
One object of this invention is to provide new and useful heterocyclic compounds and pharmaceutically acceptable salts thereof which possess activities as bradykinin agonists.
Another object of this invention is to provide processes for the preparation of said compounds and salts thereof.
A further object of this invention is to provide a pharmaceutical composition comprising, as an active ingredient, said heterocyclic compounds and pharmaceutically acceptable salts thereof.
2. Background Art
Heterocyclic compounds having activities as bradykinin antagonists have been known as described in EP-A-596,406, EP-A-622,36, WO96/04251 and W096/13485. However, it is not known that said compounds have activities as bradykinin agonists.


Disclosure of the Invention

The object heterocyclic compounds of this invention are new and can be represented by the following general formula [I]: ##STR2## wherein ##STR3## is a group of the formula: ##STR4## in which R.sup.4 is heterocyclic(lower)alkyl, and consisting of lower alkyl and acyl, or a group of the formula: ##STR5## in which R.sup.12 is hydrogen or halogen, and
The object compound [I] or its salt can be prepared by processes as illustrated in the following reaction schemes. ##STR6## Process 2 ##STR7## wherein R.sup.8 is hydrogen or lower alkyl, R.sup.9 is aryl or a heterocyclic group, each of which may be substituted with substituent(s) selected from the group consisting of amino, acyl, acylamino, lower alkyl, lower alkoxy, heterocyclic(lower)alkenyl and a heterocyclic group optionally substituted with oxo, ##STR8## are each as defined above.
In the above and subsequent description of the present specification, suitable examples of the various definitions to be included within the scope of the invention are explained in detail in the following.
The term "flower" is intended to mean a group having 1 to 6 carbon atom(s), unless otherwise provided.
In this respect, the term "lower" in lower alkenyl moieties in the various definitions is intended to mean a group having 2 to 6 carbon atoms.
Further, the term "lower" in ar(lower)alkenoyl moiety and heterocyclic(lower)alkenoyl moiety in the various definitions is intended to mean a group having 3 to 6 carbon atoms.
Suitable "lower alkyl" and lower alkyl moiety such as in the terms "heterocyclic(lower)alkyl", "acyl(lower)alkyl", etc., may be straight or branched one such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl or the like, in which preferable one is C.sub.1 -C.sub.4 alkyl such as methyl, ethyl, propyl, isobutyl or tert-butyl.
Suitable "lower alkoxy" may be straight or branched one such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentyloxy, hexyloxy or the like, in which preferable one is C.sub.1 -C.sub.4 alkoxy such as methoxy, ethoxy or isopropoxy.
Suitable lower alkenyl moiety in the term "heterocyclic(lower)alkenyl" may be a straight or branched one such as vinyl, allyl, 1-propenyl, isopropenyl, butenyl, isobutenyl, pentenyl, hexenyl or the like.
Suitable "halogen" may be fluorine, chlorine, bromine and iodine.
Suitable "acyl" and acyl moiety in the terms "acylamino" and "acyl(lower)alkyl" may be substituted or unsubstituted alkanoyl such as alkanoyl [e.g. formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, heptanoyl, 3,3-dimethylbutyryl, etc.], halo(lower)alkanoyl [e.g. chloroacetyl, trifluoroacetyl, bromoacetyl, bromobutyryl, heptafluorobutyryl, etc.], hydroxy(lower)alkanoyl [e.g. glycoloyl, lactoyl, 3-hydro

REFERENCES:
patent: 5563162 (1996-10-01), Oku et al.
patent: 5574042 (1996-11-01), Oku et al.
patent: 5708173 (1998-01-01), Oku et al.
patent: 5750699 (1998-05-01), Oku et al.

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