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US 7,452,885 B2Granted
Amino-5-(6-membered)heteroarylimidazolone compounds and the use thereof for β-secretase modulation
AssigneeWyeth
InventorsPing Zhou, Michael Sotirios Malamas, Yanfang Li, Albert Jean Robichaud, Dominick Anthony Quagliato
Life of this patent
Estimating the term…
Abstract
The present invention provides a 2-amino-5-heteroaryl-5-phenylimidazolone compound of formula I The present invention also provides methods for the use thereof to inhibit β-secretase (BACE) and treat β-amyloid deposits and neurofibrillary tangles.
Claims15
A compound of formula I
- wherein W is CO, CS or CH2;
- X is N, NO, or CR;
- Y is N, NO, or CR10;
- Z is N, NO, or CR11 with the proviso that at least one of X, Y or Z must be N or NO;
- R1 and R2 are each independently H, COR34, CO2R12 or an optionally substituted C1-C4alkyl group;
- R3 is H, OR13 or a C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl or aryl(C1-C6)alkyl group each optionally substituted;
- R4 and R5 are each independently H, halogen, NO2, CN, OR14, CO2R15, COR16, NR17R18, SOpNR19R20 or a C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl or C3-C8cycloalkyl group each optionally substituted;
- R6 is H, halogen, NO2, CN, OR21, NR22R23 or a C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl or C3-C8cycloalkyl group each optionally substituted;
- R7 is H, halogen, NO2, CN, OR24, NR25R26 or a C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, aryl or heteroaryl group each optionally substituted;
- R, R8, R9 and R10 are each independently H, halogen, NO2, CN, OR27, CO2R28, COR29, NR30R31, SOpNR32R33 or a C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl or C3-C8cycloalkyl group each optionally substituted;
- R11, R12, R13, R14, R15, R16, R21, R24, R27, R28 and R29 are each independently H or a C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, cycloheteroalkyl or aryl group each optionally substituted;
- R17, R18, R19, R20, R22, R23, R25, R26, R30, R31, R32 and R33 are each independently H, COR34, SOpR35 or a C1-C4alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8 cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted or R17, R18;
- or R19, R20, or R22, R23, or R25, R26, or R30, R31, or R32, R33 may be taken together with the atom to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing an additional heteroatom selected from O, N or S;
- R34 is H, or a C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
- and
- R35 is a C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
- or
- a tautomer thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.
15 more elements
A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and an effective amount of a compound of formula I
- wherein W is CO, CS or CH2;
- X is N, NO, or CR;
- Y is N, NO, or CR10;
- Z is N, NO, or CR11 with the proviso that at least one of X, Y or Z must be N or NO;
- R1 and R2 are each independently H, COR34, CO2R12 or an optionally substituted C1-C4alkyl group;
- R3 is H, OR13 or a C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl or aryl(C1-C6)alkyl group each optionally substituted;
- R4 and R5 are each independently H, halogen, NO2, CN, OR14, CO2R15, COR16, NR17R18, SOpNR19R20 or a C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl or C3-C8cycloalkyl group each optionally substituted;
- R6 is H, halogen, NO2, CN, OR21, NR22R23 or a C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl or C3-C8cycloalkyl group each optionally substituted;
- R7 is H, halogen, NO2, CN, OR24, NR25R26 or a C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, aryl or heteroaryl group each optionally substituted;
- R, R8, R9 and R10 are each independently H, halogen, NO2, CN, OR27, CO2R28, COR29, NR3OR31, SOpNR32R33 or a C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl or C3-C8cycloalkyl group each optionally substituted;
- R11, R12, R13, R14, R15, R16, R21, R24, R27, R28 and R29 are each independently H or a C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, cycloheteroalkyl or aryl group each optionally substituted;
- R17, R18, R19, R20, R22, R23, R25, R26, R30, R31, R32 and R33 are each independently H, COR34, SOpR35 or a C1-C4alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8 cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted or R17, R18;
- or R19, R20, or R22, R23, or R25, R26, or R30, R31, or R32, R33 may be taken together with the atom to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing an additional heteroatom selected from O, N or S;
- R34 is H, or a C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
- and
- R35 is a C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
- or
- a tautomer thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.
15 more elements
Dependencies are inferred from the claim text.