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US 2006/0052365 A1Published application
Protease inhibitors
OwnerWilliam Bondinell, Ralph Hall +4inventors
InventorsWilliam Bondinell, Ralph Hall, Qi Jin, Jeffrey Kerns, Hong Nie, Katherine Widdowson
Life of this patent
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Abstract
This invention relates 4-amino-azepan-3-ones of formula (I) which are useful as protease inhibitors, particularly of cathepsin S, and as such are useful for preventing a number of diseases amongst which are atherosclerotic lesions and pulmonary diseases such as asthma and allergic reactions.
Claims10
A method for treating a disease by inhibiting cathepsin S comprising administering at least one compound of Formula I neat or in a pharmaceutically acceptable formulation in an effective amount to a mammal in need thereof, wherein Formula I comprises:
- wherein:
- R1 is
- R2 is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar—C0-6alkyl, Het-C0-6alkyl, R9C(O)—, R9C(S)—, R9SO2—, R9OC(O)—, R9R11NC(O)—, R9R11NC(S)—, R9(R11)NSO2—
- R3 is H or substituted or unsubstituted C1-6alkyl, C3-7cycloalkylC0-6alkyl, C4-7cycloalkenylC0-6alkyl, C5-8bicycloalkylC0-6alkyl, C2-6alkenyl, C2-6alkynyl, HetC0-6alkyl, ArC0-6alkyl, Ar—ArC0-6alkyl, Ar-HetC0-6alkyl, Het-ArC0-6alkyl, or Het-HetC0-6alkyl;
- R4 is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar—C0-6alkyl, Het-C0-6alkyl, R5C(O)—, R5C(S)—, R5SO2—, R5NSO2—, R5OC(O)—, R5R12NC(O)—, or R5R12NC(S)—;
- R5 is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl-C0-6alkyl, Ar—C0-6alkyl, Ar—ArC0-6alkyl, Ar-HetC0-6alkyl, Het-ArC0-6alkyl, Het-HetC0-6alkyl, or Het-C0-6alkyl;
- R6 is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar—C0-6alkyl, or Het-C0-6alkyl;
- R7 is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar—C0-6alkyl, Het-C0-6alkyl, R10C(O)—, R10C(S)—, R10SO2—, R10OC(O)—, R10R13NC(O)—, or R10R13NC(S)—;
- R8 is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, HetC0-6alkyl or ArC0-6alkyl;
- R9 is C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar—C0-6alkyl or Het-C0-6alkyl;
- R10 is C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar—C0-6alkyl or Het-C0-6alkyl;
- R11 is H, C1-6alkyl, Ar—C0-6alkyl, or Het-C0-6alkyl;
- R12 is H, C1-6alkyl, Ar—C0-6alkyl, or Het-C0-6alkyl;
- R13 is H, C1-6alkyl, Ar—C0-6alkyl, or Het-C0-6alkyl;
- R′ is H, C1-6alkyl, Ar—C0-6alkyl, or Het-C0-6alkyl;
- R″ is H, C1-6alkyl, Ar—C0-6alkyl, or Het-C0-6alkyl;
- R′″ is C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar—C0-6alkyl, or Het-C0-6alkyl;
- X is CH2, S, or O;
- Z is C(O) or CH2;
- or
- a pharmaceutically acceptable salt, hydrate or solvate thereof.
18 more elements
A compound of Formula II
- wherein:
- R1 is:
- R2 is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar—C0-6alkyl, Het-C0-6alkyl, R9C(O)—, R9C(S)—, R9SO2—, R9OC(O)—, R9R11NC(O)—, R9R11NC(S)—, R9(R11)NSO2—
- R3 is H or substituted or unsubstituted C1-6alkyl, C3-7cycloalkylC0-6alkyl, C4-7cycloalkenylC0-6alkyl, C5-8bicycloalkylC0-6alkyl, C2-6alkenyl, C2-6alkynyl, HetC0-6alkyl, ArC0-6alkyl, Ar—ArC0-6alkyl, Ar-HetC0-6alkyl, Het-ArC0-6alkyl, or Het-HetC0-6alkyl;
- R4 is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar—C0-6alkyl, Het-C0-6alkyl, R5C(O)—, R5C(S)—, R5SO2—, R5NSO2—, R5OC(O)—, R5R12NC(O)—, or R5R12NC(S)—;
- R5 is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl-C0-6alkyl, Ar—C0-6alkyl, Ar—ArC0-6alkyl, Ar-HetC0 6alkyl, Het-ArC0-6alkyl, Het-HetC0-6alkyl, or Het-C0-6alkyl;
- R6 is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar—C0-6alkyl, or Het-C0-6alkyl;
- R7 is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar—C0-6alkyl, Het-C0-6alkyl, R10C(O)—, R10C(S)—, R10SO2—, R10OC(O)—, R10R13NC(O)—, or R10R13NC(S)—;
- R8 is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, HetC0-6alkyl or ArC0-6alkyl;
- R9 is C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar—C0-6alkyl or Het-C0-6alkyl;
- R10 is C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar—C0-6alkyl or Het-C0-6alkyl;
- R11 is H, C1-6alkyl, Ar—C0-6alkyl, or Het-C0-6alkyl;
- R12 is H, C1-6alkyl, Ar—C0-6alkyl, or Het-C0-6alkyl;
- R13 is H, C1-6alkyl, Ar—C0-6alkyl, or Het-C0-6alkyl;
- R′ is H, C1-6alkyl, Ar—C0-6alkyl, or Het-C0-6alkyl;
- R″ is C1-6alkyl, Ar—C0-6alkyl, or Het-C0-6alkyl;
- X is CH2, S, or O;
- Z is C(O) or CH2;
- or
- a pharmaceutically acceptable salt, hydrate or solvate thereof.
17 more elements
Dependencies are inferred from the claim text.