Pyridonyl guanidine F1F0-ATPase inhibitors and therapeutic uses thereof

A compound represented by Formula I:

• including all stereoisomers, geometric isomers, and tautomers;
• or a pharmaceutically acceptable salt or solvate of any of the foregoing;
• wherein:
• A1 is phenylene or a six-membered heteroarylene;
• A2 is
• X is halogen, haloalkyl, C1-C6alkoxy, —N(H)(R8), or —OP(O)(OR11)2;
• R1 represents independently for each occurrence halogen, alkyl, haloalkyl, hydroxyl, C1-C6alkoxy, or cyano;
• R2 is hydrogen or alkyl;
• R3 is aryl, aralkyl, cycloalkyl, —(C(R6)2)m-cycloalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, —(C(R6)2)m-heterocycloalkyl, alkyl, haloalkyl, hydroxylalkyl, —(C(R6)2)m-alkoxyl, or —(C(R8)2)m—CN, wherein said aryl, aralkyl, cycloalkyl, heteroaryl, heteroaralkyl, and heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, haloalkyl, hydroxyl, alkyl, cycloalkyl, C1-C6alkoxy, and cyano;
• R4 is hydrogen, alkyl, or —C(O)R7;
• or R3 and R4 are taken together with the nitrogen atom to which they are attached to form a 3 to 7 membered heterocyclic ring optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, haloalkyl, hydroxyl, alkyl, cycloalkyl, and C1-C6alkoxy;
• R5 is hydrogen, halogen, alkyl, alkoxyl, or —C(O)R7;
• R6 represents independently for each occurrence hydrogen, alkyl, or cycloalkyl;
• R7 represents independently for each occurrence alkyl or cycloalkyl;
• R8 is hydrogen or alkyl;
• R9 is alkyl, cycloalkyl, haloalkyl, —(C(R6)2)m-cycloalkyl, —(C(R6)2)m—CN, aryl, aralkyl, heteroaryl, or heteroaralkyl;
• R10 is alkyl, cycloalkyl, —(C(R6)2)m-cycloalkyl, haloalkyl, or C1-C6alkoxy;
• R11 represents independently for each occurrence hydrogen or an alkali metal;
• n is 0, 1, 2, or 3;
• and
• m is 1, 2, 3, 4, or 5.