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US 6,784,189 B2Granted
Potassium channel inhibitors and method
AssigneeBristol-Myers Squibb Company
InventorsJohn Lloyd, Heather J. Finlay, Wayne Vaccaro, Karnail S. Atwal, Michael F. Gross, Kerry L. Spear
Life of this patent
Estimating the term…
Abstract
Indanes, benzopyrans and analogues thereof are potassium channel inhibitors and blockers of IKur and have the structure where A, B, D, Q, X1, R, R1, X2 and R2 are as defined herein. These compounds are useful as antiarrhythmic agents. In addition, a method is provided for preventing cardiac arrhythmia employing the above compounds.
Claims11
A compound having the structure
- or pharmaceutically acceptable salts thereof, prodrug esters thereof, or all stereoisomers thereof, wherein
- A, B and D are each CH;
- X1 is
- (where n is 1, 2 or 3), NR6 or
- wherein the N atom is linked to the aromatic ring;
- (where R3 and R4 are independently H, alkyl, arylalkyl or cycloalkyl, or R3 and R4 can be taken together with the carbon to which they are attached to form a 5 to 8 carbon containing ring;
- and R6 is H, alkyl, alkenyl, aryl, arylalkyl, cycloalkyl or cycloalkylalkyl);
- R is H, alkyl, alkenyl, aryl, arylalkyl, heterocycloalkyl, cycloalkyl, or cycloalkylalkyl;
- R1 is alkyl, arylalkyl, aryl, alkenyl, heterocyclo, heterocycloalkyl,
- (where R5a can be any of the R5 groups), cycloalkyl, cycloalkylalkyl or
- (where R6 and R7 are independently selected from H, aryl, alkyl, arylalkyl or cycloalkyl, or R6 and R7 can be taken together with the nitrogen atom to which they are attached to form a 5 to 8 membered ring);
- or R and R1 can be taken together with the —N—S— atoms to form a 5- to 8-membered ring;
- X2 is a single bond,
- or —O— (where R8 is H, alkyl, alkenyl, aryl, arylalkyl, cycloalkyl or cycloalkylalkyl);
- R2 is H, alkyl, arylalkyl,
- or
- (where R10 and R11 are independently selected from H, alkyl, arylalkyl or cycloalkyl, or R10 and R11 can be taken together with the nitrogen to which they are attached to form a 5- to 8-membered ring);
- and
- Q is
- or
- (where R12 is alkyl, arylalkyl, aryl,
- heterocycle, heterocycloalkyl,
- (where R14 can be any of the R5 groups), alkoxy, CF3, aryloxy, arylalkoxy, cycloalkyl or cycloalkylalkyl, and where R15 and R16 are independently selected from H, alkyl, arylalkyl, aryl, heterocyclo, cycloalkyl, amino, aminoalkyl, or heterocycloalkyl, or R15 and R16 can be taken together with the nitrogen to which they are attached to form a 5- to 8-membered ring which may optionally contain an additional nitrogen atom in the ring and/or an amino group or an aminoalkyl group attached to the ring);
- and
- R13 is
- (wherein this moiety is as defined with respect to R12).
23 more elements
A method for preventing or treating cardiac arrhythmia or atrial arrhythmia, which comprises administering to a mammalian species in need of treatment a therapeutically effective amount of a compound which has the structure
- or pharmaceutically acceptable salts thereof, prodrug esters thereof, or all stereoisomers thereof, wherein
- A, B and D are each independently CH;
- X1 is
- (where n is 1, 2 or 3), NR5 or
- wherein the heteroatom in each of the above groups is linked to the aromatic ring;
- (where R3 and R4 are independently H, alkyl, arylalkyl or cycloalkyl, or R3 and R4 can be taken together with the carbon to which they are attached to form a 5 to 8 carbon containing ring;
- and
- R5 is H, alkyl, alkenyl, aryl, arylalkyl, cycloalkyl or cycloalkylalkyl);
- R is H, alkyl alkenyl, aryl, arylalkyl, heterocycloalkyl, cycloalkyl, or cycloalkylalkyl;
- R1 is alkyl arylalkyl, aryl, alkenyl, heterocyclo, heterocycloalkyl,
- (where R5a can be any of the R5 groups), cycloalkyl, cycloalkylalkyl or
- (where R6 and R7 are independently selected from H, aryl, alkyl, arylalkyl or cycloalkyl, or R6 and R7 can be taken together with the nitrogen atom to which they are attached to form a 5 to 8 membered ring);
- or R and R1 can be taken together with the —N—S— atoms to form a 5- to 8-membered ring;
- X2 is a single bond,
- or —O— (where R5 is H, alkyl, alkenyl aryl, arylalkyl, cycloalkyl or cycloalkylalkyl);
- R2 is H, alkyl, arylalkyl,
- or
- (where R10 and R11 are independently selected from H, alkyl, arylalkyl or cycloalkyl, or R10 and R11 can be taken together with the nitrogen to which they are attached to form a 5- to 8-membered ring);
- and
- Q is
- or R12-heterocycle (where R12 is alkyl, arylalkyl, aryl,
- heterocycle, heterocycloalkyl,
- (where R14 can be any of the R5 groups), CF3, alkoxy, aryloxy, arylalkoxy, cycloalkyl or cycloalkylalkyl, and where R15 and R16 are independently selected from H, alkyl, arylalkyl, aryl, heterocyclo, amino, aminoalkyl, cycloalkyl or heterocycloalkyl, or R15 and R16 can be taken together with the nitrogen to which they are attached to form a 5- to 8-membered ring which may optionally contain an additional nitrogen atom in the ring and/or an amino group or an aminoalkyl group attached to the ring);
- and
- R13 is
- (wherein this moiety is as defined with respect to R12).
23 more elements
Dependencies are inferred from the claim text.