Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1988-09-23
1989-10-17
Ramsuer, Robert W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
5142345, 5142352, 514253, 514269, 514272, 514313, 514314, 514316, 514318, 514322, 514323, 514333, 514338, 514339, 514386, 514387, 514388, 514392, 514394, 514395, 514397, 514404, 514407, 514414, 514419, 544 80, 544121, 544122, 544123, 544128, 544130, 544131, 544139, 544140, 544144, 544295, 544296, 544322, 544328, 544331, 544357, 544360, 544363, 544364, 544370, 544371, 544373, 546160, 546162, 546168, 546169, 546171, 546187, 546193, 546194, 546199, 546201, 546256, 546271, 546273, 548301, 548305, 548327, 548328
Patent
active
048747599
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to 5-hydroxyindole-3-carboxylic acid amide compounds and their acid addition salts which are novel and of use as diuretics or therapeutic medicines for circulation system diseases.
BACKGROUND ART
With an increase in the population of aged people, various diseases of circulation systems, particularly cerebral and cardiac circulation system diseases caused by atheroclerosis, hypertension, etc. have become a serious social problem. As the therapeutic medicines for such diseases, useful medicaments are those which have hyperkinemic actions, particularly those which exhibit vasodilating actions on cerebral blood vessels and coronary blood vessels, or those which have diuretic actions.
Also, in recent years, better use have been made of the medicaments which have anti-platelet aggregation actions for the treatment of thrombotic diseases. Furthermore, in view of the fact that leucotrienes which are metabolically produced by 5-lipoxygenase on arachidonic acid cascade possess potent coronary vasospasm, attention has been paid to the relationship between cardiac diseases such as angina pectoris and leukotrienes. Therefore it is said that the compounds which have 5-lipoxygenase-inhibitory actions are of use for the treatment of such circulatory diseases.
In U.S. Pat. No. 2852527 and Journal of Medicinal Chemistry, vol. 10, p. 264 (1967), there are described lower alkyl esters of 2-lower alkyl-5-hydroxy-4-tertiary-aminoindole-3-carboxylic acids which have central nervous system-stimulating actions and hypoglycemic actions.
However, the forementioned known compounds have high toxicity, and there has not been any suggestion about pharmacological actions against circulatory diseases.
In the specification of U.S. Pat. No. 4581355, there are disclosed some species of indole-3-carboxamide compounds, which have 5-lipoxygenase actions, antihypertensive actions or cardiac actions, but these compounds do not exhibit any diuretic actions.
DISCLOSURE OF THE INVENTION
For the purpose of developing compounds which are useful as diuretics, the present inventors have intensively conducted studies to find that novel 5-hydroxyindole-3-carboxylic acid amide compounds and their acid addition salts have antihypertensive actions, cerebral vasodilating actions, coronary vasodilating actions, anti-platelet aggregation actions and/or 5-lipoxygenase-inhibiting actions besides excellent diuretic actions, and that thus they are useful as diuretics, antihypertensive agents and therapeutic agents for cerebral and cardiac circulation system diseases. These findings have resulted in the completion of the present invention.
That is, the present invention relates to 5-hydroxyindole-3-carboxylic acid amide compounds of the general formula: ##STR2## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are, the same or different, independently a hydrogen atom, an alkyl group, an aryl group, an aralkyl group or a heteroaryl group, or R.sup.1 and R.sup.2 and/or R.sup.3 and R.sup.4 respectively are combined to each other to form a heterocyclic group as taken together with the adjacent nitrogen atom, R.sup.5 is an alkyl group, R.sup.6 is a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group or an aralkyl group and X is a hydrogen atom, a halogen atom or a lower alkanoyl group, or their acid addition salts.
With reference to the above-mentioned substituents, the halogen atom represents chlorine, bromine, fluorine or iodine atom, the alkyl group represents a straight- or branched-chain alkyl having 1 to 8 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, 2-ethylhexyl or 1,1,3,3-tetramethylbutyl, the lower alkanoyl group represents an alkanoyl having 2 to 5 carbon atoms such as acetyl, propionyl, butyryl, pivaloyl or valeryl, the cycloalkyl group represents a cycloalkyl having 3 to 7 carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl, the aryl group represents phenyl, naphthyl or so on
REFERENCES:
Bell et al, J. Med. Chem., vol. 10, pp. 264-266 (1967).
Hakamada Ichiro
Ikebe Tsuguo
Tahara Tetsuya
Yaoka Osamu
Ramsuer Robert W.
Yoshitomi Pharmaceutical Industries Ltd.
LandOfFree
5-Hydroxyindole-3-carboxylic acid amide compounds, pharmaceutica does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 5-Hydroxyindole-3-carboxylic acid amide compounds, pharmaceutica, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 5-Hydroxyindole-3-carboxylic acid amide compounds, pharmaceutica will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1743753