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US 2005/0239781 A1Published application
Beta-carbolines useful for treating inflammatory disease
AssigneeMillennium Pharmaceuticals, Inc.
InventorsMichael Hepperle, Julie Liu, Francois Soucy, Prakash Raman, Jeremy Little, Paul Fleming, Dominic Reynolds, Geraldine Harriman
Life of this patent
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Abstract
This invention provides beta-carboline compounds of formula III-A-aa: wherein Q, G, R1, R2, R3, and R6b are as described in the specification. The compounds are useful for treating diseases such as inflammatory diseases and cancer.
Claims27
A compound of formula III-A-aa:
- or a pharmaceutically acceptable salt thereof wherein,
- Q is —CH2— or —CH(R9)—;
- G is —NR4R5 or a 3-10 membered monocyclic or bicyclic heterocyclyl ring that is optionally substituted by 1-4 R10;
- R1 is hydrogen, halo, C1-2 alkyl, amino, or (C1-2 alkyl)1-2 amino;
- R2 is hydrogen, halo, C1-4 aliphatic, C1-2 alkoxy, or C1-2 haloalkyl;
- R3 is hydrogen, halo, C1-2 aliphatic, C1-2 alkoxy, or C1-2 haloalkyl;
- R4 is hydrogen or optionally substituted C1-6 aliphatic;
- R5 is:
- a) an optionally substituted group selected from aryl, heteroaryl, heterocyclyl, or carbocyclyl, or
- b) a C1-6 aliphatic group that is optionally substituted by:
- halo, —OR7, —CN, —SR8, —S(O)2R8, —C(O)R7, —CO2R7, —N(R7)2, —C(O)N(R7)2, —N(R7)C(O)R7, —N(R7)CO2R8, —SO2N(R7)2, —NR7SO2R7, —N(R7)C(O)N(R7)2, or an aryl, heteroaryl, heterocyclyl, or carbocyclyl group that is optionally further substituted by C1-6aliphatic, —CF3, halo, —OR7, —CN, —SR8, —S(O)2R8, —C(O)R7, —CO2R7, —N(R7)2, —C(O)N(R7)2, —N(R7)C(O)R7, —N(R7)CO2R8, —SO2N(R7)2, —NR7SO2R7, —N(R7)C(O)N(R7)2;
- each R6b is independently selected from hydrogen or a C1-6 aliphatic;
- each R7 is independently selected from hydrogen or an optionally substituted C1-4 aliphatic, or two R7 on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted 3-6 membered heteroaryl or heterocyclyl ring;
- each R7a is independently selected from hydrogen or an optionally substituted group selected from C1-4 aliphatic, aryl, heteroaryl, heterocyclyl, or carbocyclyl, or two R7a on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted 3-6 membered heteroaryl or heterocyclyl ring;
- each R8 is independently an optionally substituted C1-4 aliphatic;
- each R8a is independently an optionally substituted group selected from C1-4 aliphatic, aryl, heteroaryl, heterocyclyl, or carbocyclyl;
- R9 is a C1-3 aliphatic;
- each R10 is independently selected from ═O, R11, T-R11, or V-T-R11, or two occurrences of R10, taken together with the atom(s) to which they are bound, form an optionally substituted monocyclic or bicyclic 3-8-membered aryl, heteroaryl, heterocyclyl, or carbocyclyl ring;
- each R11 is independently selected from —CF3, halo, —OR7a, —CN, —SR8a, —S(O)2R8a, —C(O)R7a, —CO2R7a, —N(R7a)2, —C(O)N(R7a)2, —N(R7)C(O)R7a, —N(R7)CO2R7a, —SO2N(R7a)2, —N(R7)SO2R7a, —N(R7)C(O)N(R7a)2 or an optionally substituted group selected from C1-6aliphatic, aryl, heteroaryl, heterocyclyl or carbocyclyl;
- T is a straight or branched C1-4 alkylene chain;
- and
- V is —O—, —N(R7)—, —S—, —S(O)—, —S(O)2—, —C(O)—, or —CO2—.
19 more elements
A compound of formula III-A-aa:
- or a pharmaceutically acceptable salt thereof wherein,
- Q is —CH2— or —CH(R9)—;
- G is —NR4R5 or a 3-7 membered heterocyclyl ring that is optionally substituted by 1-4 R10;
- R1 is hydrogen, halo, C1-2 alkyl, amino, or (C1-2 alkyl)1-2 amino;
- R2 is hydrogen, halo, C1-2 aliphatic, C1-2 alkoxy, or C1-2 haloalkyl;
- R3 is hydrogen, halo, C1-2 aliphatic, C1-2 alkoxy, or C1-2 haloalkyl;
- R4 is hydrogen or C1-6 aliphatic;
- R5 is a C1-6 aliphatic group that is optionally substituted by halo, —OR7, —CN, —SR8, —S(O)2R8, —C(O)R7, —CO2R7, —N(R7)2, —C(O)N(R7)2, —N(R7)C(O)R7, —N(R7)CO2R7, or —N(R7)C(O)N(R7)2;
- each R6b is independently selected from hydrogen or a C1-6 aliphatic;
- each R7 is independently selected from hydrogen or C1-4 aliphatic, or two R7 on the same nitrogen atom are taken together with the nitrogen to form a 5-6 membered heteroaryl or heterocyclyl ring;
- R8 is C1-4 aliphatic;
- R9 is a C1-3 aliphatic;
- each R10 is independently selected from ═O, R11, T-R11, or V-T-R11;
- each R11 is independently selected from C1-6 aliphatic, —CF3, halo, —OR7, —CN, —SR8, —S(O)2R8, —C(O)R7, —CO2R7, —N(R7)2, —C(O)N(R7)2, —N(R7)C(O)R7, —N(R7)CO2R7, or —N(R7)C(O)N(R7)2;
- T is a straight or branched C1-4 alkylene chain;
- and
- V is —O—, —N(R7)—, —S—, —S(O)—, —S(O)2—, —C(O)—, or —CO2—.
14 more elements
A compound of formula III-A-aa:
- or a pharmaceutically acceptable salt thereof wherein,
- Q is —CH2— or —CH(R9)—;
- G is —NR4R5 or a 3-7 membered heterocyclyl ring that is optionally substituted by 1-2 R10;
- R1 is hydrogen, halo, C1-2 alkyl, amino, or (C1-2 alkyl)1-2 amino;
- R2 is hydrogen, halo, C1-2 aliphatic, C1-2 alkoxy, or C1-2 haloalkyl;
- R3 is hydrogen, halo, C1-2 aliphatic, C1-2 alkoxy, or C1-2 haloalkyl;
- R4 is hydrogen or C1-6 aliphatic;
- R5 is a C1-6 aliphatic group that is optionally substituted by halo, —OR7, —CN, —SR8, —S(O)2R8, —C(O)R7, —CO2R7, —N(R7)2, —C(O)N(R7)2, —N(R7)C(O)R7, —N(R7)CO2R8, or —N(R7)C(O)N(R7)2;
- each R6b is independently selected from hydrogen or a C1-6 aliphatic;
- each R7 is independently selected from hydrogen or C1-4 aliphatic, or two R7 on the same nitrogen atom are taken together with the nitrogen to form a 5-6 membered heteroaryl or heterocyclyl ring;
- each R8 is independently C1-4 aliphatic;
- R9 is a C1-3 aliphatic;
- each R10 is independently selected from R11, T-R11, or V-T-R11;
- each R11 is independently selected from C1-6 aliphatic, halo, —OR7, —CN, —SR8, —S(O)2R8, —C(O)R7, —CO2R7, —N(R7)2, —C(O)N(R7)2, —N(R7)C(O)R7, —N(R7)CO2R7, or —N(R7)C(O)N(R7)2;
- T is a straight or branched C1-4 alkylene chain;
- and
- V is —O—, —N(R7)—, —S—, —S(O)—, —S(O)2—, —C(O)—, or —CO2—.
14 more elements
A compound, or a pharmaceutically acceptable salt thereof, selected from:
A compound, or a pharmaceutically acceptable salt thereof, selected from:
Dependencies are inferred from the claim text.