Heterocyclic compound and cardiotonic agent containing the same

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...

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514242, 514253, 544 8, 544182, 544253, A61K 3154, C07D28516, C07D25306, C07D23704

Patent

active

054460425

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to heterocyclic compounds represented by the formula (I) or pharmaceutically acceptable acid addition salts thereof and cardiotonic agents containing the heterocyclic compounds as effective components: ##STR1## wherein R and R.sub.1 represent hydrogen atom or lower alkyl group; R.sub.2 and R.sub.3 may be independently same or different and represent hydrogen atom, lower alkyl group, lower alkoxy group, trifluoromethyl group, halogen atom, nitro group, amino group, cyano group or hydroxyl group or R.sub.2 and R.sub.3 are joined to form methylenedioxy group or ##STR2## forms naphthalene; and A-E represents ##STR3## wherein R.sub.4 and R.sub.5 represent hydrogen atom or lower alkyl group.


BACKGROUND ART

Compounds represented by the following formula (II) are known as heterocyclic compounds having cardiotonic activity and are disclosed for example in Japanese Patent Provisional Publication (Kokai) Nos. 57-2284 and 58-131981 and Japanese Patent Publication (Kokoku) No. 61-53350. ##STR4## wherein R.sub.1 and A-E are as defined above.
These known heterocyclic compounds having cardiotonic activities were clinically unfavorable since they have not so strong cardiotonic activities and increase heart rate.
We, the inventors carried out studies to succeed in synthesizing novel heterocyclic compounds having excellent positive inotropic effect as cardiotonic agent and suppressing increase of heart rate, by modifying the pyridyl group in the compound of the formula (II), thus completing the present invention. More specifically, the present invention is directed to tetrahydropyridine derivatives represented by the above-mentioned formula (I) or pharmaceutically acceptable acid addition salts thereof and cardiotonic agents containing them as effective components.


DISCLOSURE OF THE INVENTION

The terms used for definition of letters in the above-mentioned formula by which the compounds of the present invention are represented are defined and exemplified in the following.
The wording "lower" refers to a group having 1 to 6 carbon atoms unless otherwise indicated.
The "lower alkyl group" refers to a straight- or branched-chain alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, n-hexyl or the like.
The "lower alkoxy group" refers to a straight- or branched-chain alkoxy group such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, n-pentyloxy, n-hexyloxy or the like.
The "halogen atom" may be fluorine, chlorine, bromine or iodine atom.
The compound according to the present invention is for example as follows: iadiazin-5-one H-1,3,4-thiadiazin-5-one H-1,3,4-thiadiazin-5-one H-1,3,4-thiadiazin-5-one 4H,6H-1,3,4-thiadiazin-5-one H,6H-1,3,4-thiadiazin-5-one H-1,3,4-thiadiazin-5-one H-1,3,4-thiadiazin-5-one H-1,3,4-thiadiazin-5-one H-1,3,4-thiadiazin-5-one 4H,6H-1,3,4-thiadiazin-5-one 4H,6H-1,3,4-thiadiazin-5-one 5,6-tetrahydropyrid-4-yl]-4H,6H-1,3,4-thiadiazin-5-one 5,6-tetrahydropyrid-4-yl]-4H,6H-1,3,4-thiadiazin-5-one 5,6-tetrahydropyrid-4-yl]-4H,6H-1,3,4-thiadiazin-5-one 5,6-tetrahydropyrid-4-yl]-4H,6H-1,3,4-thiadiazin-5-one 5,6-tetrahydropyrid-4-yl]-4H,6H-1,3,4-thiadiazin-5-one 5,6-tetrahydropyrid-4-yl]-4H,6H-1,3,4-thiadiazin-5-one -4H,6H-1,3,4-thiadiazin-5-one d-4-yl]-4H,6H-1,3,4- thiadiazin-5-one -1,3,4-thiadiazin-5-one -1,3,4-thiadiazin-5-one -1,3,4-thiadiazin-5-one -1,3,4-thiadiazin-5-one -1,3,4-thiadiazin-5-one -4-yl]-4H,6H-1,3,4-thiadiazin-5-one -4-yl]-4H,6H-1,3,4-thiadiazin-5-one thyl-4H,6H-1,3,4-thiadiazin-5-one ethyl-4H,6H-1,3,4-thiadiazin-5-one thyl-4H,6H-1,3,4-thiadiazin-5-one dimethyl-4H,6H-1,3,4-thiadiazin-5-one yl]-4H,6H-1,3,4-thiadiazin-5-one thyl-4H,6H-1,3,4-thiadiazin-5-one thyl-4H,6H-1,3,4-thiadiazin-5-one dimethyl-4H,6H-1,3,4-thiadiazin-5-one hyl-4H,6H-1,3,4-thiadiazin-5-one hyl-4H,6H-1,3,4-thiadiazin-5-one ethyl-4H,6H-1,3,4-thiadiazin-5-one -dimethyl-4H,6H-1,3,4-thiadiazin-5-one ethyl]-1,2,5,6-tetrahydropyrid-4-yl]-4H,6H-1,3,4-thiadiazin-5-one hyl-4H,6H-1,3,4-thiadiazin-5-one 4H,6H-1,3,4-thiadiazin-5-one 6H

REFERENCES:
patent: 4486431 (1984-12-01), Lesher et al.
patent: 4489073 (1984-12-01), Hargreaves et al.
patent: 4558045 (1985-12-01), Hargreaves et al.
patent: 4716164 (1987-12-01), Hargreaves et al.
patent: 4788194 (1988-11-01), Hargreaves et al.

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