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US 2002/0165264 A1Published application
Aminal diones as potassium channel openers
AssigneeAbbott Laboratories
InventorsMichael E. Kort, Robert J. Gregg, William A. Carroll, Arturo Perez Medrano, Jurgen Dinges, Fatima Z. Basha
Life of this patent
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Abstract
Compounds of formula (I) 1 may be useful in treating diseases prevented by or ameliorated with potassium channel openers. Also disclosed are potassium channel opening compositions and a method of opening potassium channels in a mammal.
Claims71
A compound of formula (I)
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- or a pharmaceutically acceptable salt thereofwherein
- A is selected from the group consisting of
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- and S(O)2;
- X is selected from the group consisting of CH2, O and N(Z);
- Z is selected from the group consisting of hydrogen and alkyl;
- R1 is selected from the group consisting of aryl, arylalkyl, heterocycle and heterocyclealkyl;
- R2, R3 and R4 are independently selected from the group consisting of hydrogen and alkyl;
- R5 is selected from the group consisting of aryl, arylalkenyl, arylalkyl, aryloxyalkyl, heterocycle and heterocyclealkyl;
- R6 is selected from the group consisting of hydrogen, alkenyl, alkenyloxyalkyl, alkenyloxy(alkenyloxy)alkyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkoxycarbonyl(halo)alkyl, alkoxy(halo)alkyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyl(halo)alkyl, alkylcarbonyloxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkylthioalkyl, alkynyl, aryl, arylalkoxyalkyl, arylalkoxycarbonyl, arylalkoxycarbonylalkyl, arylalkyl, arylcarbonyl, arylcarbonylalkyl, arylcarbonyloxyalkyl, aryl(halo)alkyl, aryloxyalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, arylalkylthioalkyl, arylsulfonylalkyl, carboxy, carboxyalkyl, carboxyhalo)alkyl, cyanoalkyl, cyano(halo)alkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkyl, cycloalkylalkoxyalkyl, cycloalkylalkyl, cycloalkylcarbonyl, cycloalkyloxyalkyl, cycloalkylalkylthioalkyl, formyl, haloalkenyl, haloalkyl, haloalkylcarbonyl, haloalkynyl, heterocycle, heterocyclealkoxyalkyl, heterocyclealkyl, heterocyclecarbonyl, heterocycleoxyalkyl, heterocyclealkylthioalkyl, hydroxyalkyl, mercaptoalkyl, sulfamylalkyl, sulfamyl(halo)alkyl, (NR9R10)alkyl, (NR9R10)carbonyl and (NR9R10)carbonylalkyl;
- R7 is selected from the group consisting of hydrogen, haloalkyl, and lower alkyl;
- or
- R6 and R7 taken together with the carbon atom to which they are attached, together form a 5 or 6 membered carbocyclic ring wherein the 5 or 6 membered carbocyclic ring is optionally substituted with 1 or 2 substituents independently selected from the group consisting of alkenyl, alkoxy, alkyl, alkynyl, halogen, haloalkoxy, and haloalkyl;
- R9 and R10 are independently selected from the group consisting of hydrogen, alkoxysulfonyl, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, arylalkyl, arylcarbonyl, arylsulfonyl and formyl.
12 more elements
A method of treating a disorder in a host mammal in need of such treatment comprising administering to the mammal a therapeutically effective amount of a compound of formula (I).
A process for the preparation of a compound of formula (V)
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- wherein
- R1 is selected from the group consisting of aryl, arylalkyl, heterocycle and heterocyclealkyl;
- R2, R3 and R4 are independently selected from the group consisting of hydrogen and alkyl;
- R5 is selected from the group consisting of aryl, arylalkyl, heterocycle and heterocyclealkyl;
- R6 is selected from the group consisting of hydrogen, alkenyl, alkenyloxyalkyl, alkenyloxy(alkenyloxy)alkyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkoxycarbonyl(halo)alkyl, alkoxy(halo)alkyl, alkyl, allylcarbonyl, alkylcarbonylalkyl, alkylcarbonyl(halo)alkyl, alkylcarbonyloxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkylthioalkyl, allkynyl, amido, amidoalkyl, aryl, arylalkoxyalkyl, arylalkoxycarbonyl, arylalkoxycarbonylalkyl, arylalkyl, arylcarbonyl, arylcarbonylalkyl, arylcarbonyloxyalkyl, aryl(halo)alkyl, aryloxyalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, arylalkylthioalkyl, arylsulfonylalkyl, carboxy, carboxyalkyl, carboxy(halo)alkyl, cyanoalkyl, cyano(halo)alkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkyl, cycloalkylalkoxyalkyl, cycloalkylalkyl, cycloalkylcarbonyl, cycloalkyloxyalkyl, cycloalkylalkylthioalkyl, formyl, haloalkenyl, haloalkyl, haloaLkylcarbonyl, haloalkynyl, heterocycle, heterocyclealkoxyalkyl, heterocyclealkyl, heterocyclecarbonyl, heterocycleoxyalkyl, heterocyclealkylthioalkyl, hydroxyalkyl, mercaptoalkyl, sulfamylalkyl, sulfamyl(halo)alkyl and (NR9R10)alkyl;
- and
- R9 and R10 are independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, aryl, arylalkyl, arylcarbonyl, formyl, and S(O)2R11 wherein R11 is selected from the group consisting of alkoxy, alkyl, aryl and arylalkyl;
- the process comprising:
- (a) reacting an aldehyde of formula (VI)
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- an amide of formula (VII)
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- 1H-benzotriazole-polystyrene resin and an acid in a first solvent at about 50° C. to about 80° C., wherein R4, R5 and R6 are as defined above;
- (b) reacting the product of step (a), a base and a compound of formula (VIII)
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- in a second solvent wherein R1, R2 and R3 are as defined above to provide a compound of formula (V).
14 more elements
Dependencies are inferred from the claim text.