Pharmaceutical composition and method for treating cardiovascular diseases using substituted anilides and sulfonamides
First Claim
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1. A method for the treatment of myocardial ischemia and arrhythmia comprising administering to a mammalian specie in need thereof a therapeutically effective amount of a compound having the formula ##STR17## and to acid addition salts and quaternary ammonium salts thereof, wherein R and R1 each independently represent hydrogen, halo, lower alkyl, lower alkoxy, trihalomethyl, nitro, amino or hydroxy;
- X represents oxa (--O--) or thia (--S--);
B represents a basic nitrogen-containing radical of the formula ##STR18## A and A'"'"' are independently selected from hydrogen or lower alkyl;
m is zero or an integer from 1 to 3;
n represents an integer from 2-5;
p and p'"'"' are the same or different integer of 1 to 3;
##STR19## R2 is lower alkyl, aryl, aralkyl, cycloalkyl(lower alkyl), lower alkenyl, lower alkadienyl, α
-substituted phenyl alkyl, aralkenyl, aralkynyl or heteroaryl; and
R3 and R4 are independently selected from hydrogen, lower alkyl, hydroxy lower alkyl, R substituted phenyl lower alkyl, R substituted cinnamoyl, 2- or 4-pyridylaklyl, and N-(lower alkyl)phenyl-(lower alkyl);
or R3 and R4 taken together with the nitrogen atom to which they are attached form a 5- to 7-membered monocyclic heterocycle which may contain one oxygen atom or one additional nitrogen atom and which heterocycle may be substituted by 1, 2 or 3 lower alkyl, lower alkoxy, hydroxy lower alkyl or lower alkanoyloxy-lower alkyl groups.
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Abstract
A novel pharmaceutical composition and method is disclosed for the treatment of cardiovascular diseases, e.g. myocardial ischemia and/or arrhythmia. The method and composition include an effective amount of a compound of the formula ##STR1## wherein X, Y, R, R1, A, A'"'"', m, n, p, p'"'"' and B are as defined herein.
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38 Claims
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1. A method for the treatment of myocardial ischemia and arrhythmia comprising administering to a mammalian specie in need thereof a therapeutically effective amount of a compound having the formula ##STR17## and to acid addition salts and quaternary ammonium salts thereof, wherein R and R1 each independently represent hydrogen, halo, lower alkyl, lower alkoxy, trihalomethyl, nitro, amino or hydroxy;
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X represents oxa (--O--) or thia (--S--); B represents a basic nitrogen-containing radical of the formula ##STR18## A and A'"'"' are independently selected from hydrogen or lower alkyl;
m is zero or an integer from 1 to 3;n represents an integer from 2-5; p and p'"'"' are the same or different integer of 1 to 3;
##STR19## R2 is lower alkyl, aryl, aralkyl, cycloalkyl(lower alkyl), lower alkenyl, lower alkadienyl, α
-substituted phenyl alkyl, aralkenyl, aralkynyl or heteroaryl; andR3 and R4 are independently selected from hydrogen, lower alkyl, hydroxy lower alkyl, R substituted phenyl lower alkyl, R substituted cinnamoyl, 2- or 4-pyridylaklyl, and N-(lower alkyl)phenyl-(lower alkyl);
or R3 and R4 taken together with the nitrogen atom to which they are attached form a 5- to 7-membered monocyclic heterocycle which may contain one oxygen atom or one additional nitrogen atom and which heterocycle may be substituted by 1, 2 or 3 lower alkyl, lower alkoxy, hydroxy lower alkyl or lower alkanoyloxy-lower alkyl groups. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38)
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Current AssigneeE R Squibb & Sons Incorporated
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Original AssigneeE R Squibb & Sons Incorporated
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InventorsKrapcho, John, Bergey, James L., Grover, Gary J.
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Primary Examiner(s)Waddell, Frederick E.
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Assistant Examiner(s)Criares, T. J.
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Application NumberUS07/471,254Time in Patent Office851 DaysField of Search514/599, 514/354, 514/613, 514/614, 514/629, 514/255, 514/601, 514/617US Class Current514/354CPC Class CodesA61K 31/165 having aromatic rings, e.g....A61K 31/18 Sulfonamides compounds cont...A61P 3/00 Drugs for disorders of the ...A61P 3/14 for calcium homeostasis vit...A61P 9/00 Drugs for disorders of the ...A61P 9/06 AntiarrhythmicsA61P 9/08 Vasodilators for multiple i...A61P 9/10 for treating ischaemic or a...C07C 233/29 having the carbon atom of t...C07C 2601/14 The ring being saturatedC07C 323/41 Y being a hydrogen or an ac...C07C 323/42 Y being a carbon atom of a ...C07D 213/81 Amides; Imides
