Substituted 2-aminoacetamides and the use thereof

A method for treating, or ameliorating neuronal loss following global and focal ischemia;

• treating, preventing or ameliorating pain;
• treating, or ameliorating manic depression;
• providing local anesthesia;
• or treating arrhythmias, comprising administering to a mammal in need of such treatment an effective amount of a compound having the Formula II:
• or a pharmaceutically acceptable salt or prodrug thereof, wherein:
• R1, R2, R3 and R4 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl;
• R5, R6 and R7 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl, or R5, is defined as above, and R6 and R7 together with the nitrogen atom to which they are attached form a heterocycle selected from the group consisting of piperidine, piperazine, and morpholine;
• A1 and A2 are as follows:
• A1 is aryl, or saturated or partially unsaturated carbocycle and A2 is heteroaryl, or saturated or partially unsaturated heterocycle;
• or
• A1 is heteroaryl, or saturated or partially unsaturated heterocycle, and A2 is aryl, or saturated or partially unsaturated carbocycle;
• wherein any of A1 or A2 may be optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, aryl, cycloalkyl, heteroaryl, alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, cycloalkylalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, alkoxyalkyl, nitro, amino, ureido, cyano, alkanoylamino, hydroxy, thiol, alkanoyloxy, azido, alkoxy, carboxy, aminocarbonyl, and alkylthiol;
• when A1 or A2 is heterocycle, the heterocycle is selected from the group consisting of piperdinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl, and tetrahydropyranyl;
• X is one or O, S, NR8, CH2, C(O), NR8C(O), C(O)NR8, SO, SO2 or a covalent bond;
• where
• R8 is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl;
• and
• n is 0, 1, 2 or 3;
• and
• wherein said prodrug is the corresponding ester or amide to one or more hydroxyalkyl or aminoalkyl when one or more of R1-R7 is hydroxyalkyl or aminoalkyl.