2-Amino-5-piperidinylimidazolone compounds and use thereof for beta-secretase modulation

A method for the treatment of a disease or disorder associated with excessive BACE activity in a patient in need thereof which comprises providing to said patient a therapeutically effective amount of a compound of formula I

• wherein
• R is H, COR7, CO2R7, CONR8R9, SO2NR8R9, SOmR10, or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R1, R2, and R3 are each independently H or an alkyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted or R1 and R2 may be taken together with the atom to which they are attached form an optionally substituted 5- to 7-membered ring optionally interrupted by an additional heteroatom selected from O, N or S;
• R4, R5, and R6 are each independently H, halogen, NO2, CN, OR11, COR11, CO2R11, CONR12R13, NR12R13, NR12COR14, NR12SO2R14, S02NR12R13, SOnR14 or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted or when attached to adjacent carbon atoms R4 and R5 or R5 and R6 may be taken together with the atoms to which they are attached to form an optionally substituted 5- to7-membered ring optionally interrupted by one, two or three heteroatoms selected from O, N or S;
• m and n are each independently 0,1 or 2;
• R7 and R11 are each independently H or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R8, R9, R12 and R13 are each independently H, OR15, COR15, CO2R15 or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted or R8 and R9 or R12 and R13 may be taken together with the atom to which they are attached to form an optionally substituted 5- to 7-membered ring optionally interrupted by an additional heteroatom selected from O, N or S;
• R10 and R14 are each independently an alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R15 is H or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R16, R17 and R18 are each independently H, halogen, CN, OR19 or an alkyl, cycloalkyl, cyclohetereoalkyl, aryl or heteroaryl group each optionally substituted;
• and
• R19 is H or an alkyl, cycloalkyl, cyclohetereoalkyl, aryl or heteroaryl group each optionally substituted;
• or
• a tautomer thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and an effective amount of a compound of formula I

• wherein
• R is H, COR7, CO2R7, CONR8R9, SO2NR8R9, SOmR10, or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R1, R2, and R3 are each independently H or an alkyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted or R1 and R2 may be taken together with the atom to which they are attached form an optionally substituted 5- to 7-membered ring optionally interrupted by an additional heteroatom selected from O, N or S;
• R4, R5, and R6 are each independently H, halogen, NO2, CN, OR11, COR11, CO2R11, CONR12R13, NR12R13, NR12COR14, NR12SO2R14, SO2NR12R13, SOnR14 or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted or when attached to adjacent carbon atoms R4 and R5 or R5 and R6 may be taken together with the atoms to which they are attached to form an optionally substituted 5- to7-membered ring optionally interrupted by one, two or three heteroatoms selected from O, N or S;
• m and n are each independently 0,1 or 2;
• R7 and R11 are each independently H or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R8, R9, R12 and R13 are each independently H, OR15, COR15, CO2R15 or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted or R8 and R9 or R12 and R13 may be taken together with the atom to which they are attached to form an optionally substituted 5- to 7-membered ring optionally interrupted by an additional heteroatom selected from O, N or S;
• R10 and R14 are each independently an alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R15 is H or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R16, R17 and R18 are each independently H, halogen, CN, OR19 or an alkyl, cycloalkyl, cyclohetereoalkyl, aryl or heteroaryl group each optionally substituted;
• and
• R19 is H or an alkyl, cycloalkyl, cyclohetereoalkyl, aryl or heteroaryl group each optionally substituted;
• or
• a tautomer thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.