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US 2014/0275092 A1Published application
Pyrazolo compounds and uses thereof
AssigneeConstellation Pharmaceuticals, Inc.
InventorsBrian K. Albrecht, Steven F. Bellon, Victor S. Gehling, Jean-Christophe Harmange
Life of this patent
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Abstract
The present invention relates to compounds useful as inhibitors of one or more histone demethylses. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.
Claims23
A compound of formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is —R, halogen, —OR, —SR, —N(R′)2, —CN, —NO2, —C(O)R, —CO2R, —C(O)N(R′)2, —C(O)SR, —C(O)C(O)R, —C(O)CH2C(O)R, —C(S)N(R′)2, —C(S)OR, —S(O)R, —SO2R, —SO2N(R′)2, —N(R′)C(O)R, —N(R′)C(O)N(R′)2, —N(R′)SO2R, —N(R′)SO2N(R′)2, —N(R′)N(R′)2, —N(R′)C(═N(R′))N(R′)2, —C═NN(R′)2, —C═NOR, —C(═N(R′))N(R′)2, —OC(O)R, or —OC(O)N(R′)2;
- each R is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- each R′ is independently —R, —C(O)R, —CO2R, or two R′ on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
- Ring A is
- R2 and R3 are independently —R, halogen, —OR, —SR, —N(R′)2, —CN, —NO2, —C(O)R, —CO2R, —C(O)N(R′)2, —C(O)SR, —C(O)C(O)R, —C(O)CH2C(O)R, —C(S)N(R′)2, —C(S)OR, —S(O)R, —SO2R, —SO2N(R′)2, —N(R′)C(O)R, —N(R′)C(O)N(R′)2, —N(R′)SO2R, —N(R′)SO2N(R′)2, —N(R′)N(R′)2, —N(R′)C(═N(R′))N(R′)2, —C═NN(R′)2, —C═NOR, —C(═N(R′))N(R′)2, —OC(O)R, or —OC(O)N(R′)2;
- or:
- R2 and R3 are taken together with their intervening atoms to form an optionally substituted 5-7 membered partially unsaturated or aromatic fused ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
- R2′ is —R, —OR, —SR, —N(R′)2, —C(O)R, —CO2R, —C(O)N(R′)2, —C(O)SR, —C(O)C(O)R, —C(O)CH2C(O)R, —C(S)N(R′)2, —C(S)OR, —S(O)R, —SO2R, —SO2N(R′)2, —N(R′)C(O)R, —N(R′)C(O)N(R′)2, —N(R′)SO2R, —N(R′)SO2N(R′)2, —N(R′)N(R′)2, —N(R′)C(═N(R′))N(R′)2, —C═NN(R′)2, —C═NOR, —C(═N(R′))N(R′)2, —OC(O)R, or —OC(O)N(R′)2;
- or:
- R2′ and R3 are taken together with their intervening atoms to form an optionally substituted 5-7 membered partially unsaturated or aromatic fused ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
- X is —N(R4)—, —O—, or —S—;
- R4 is —R, —C(O)R, —CO2R, or —S(O)2R;
- or:
- R4 and R3 are taken together with their intervening atoms to form an optionally substituted 5-7 membered saturated, partially unsaturated, or aromatic fused ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
- R5 is R, —C(O)R, —CO2R, —C(O)N(R′)2, —C(O)C(O)R, or —C(O)CH2C(O)R;
- or:
- R5 and R2 are taken together with their intervening atoms to form an optionally substituted 5-7 membered partially unsaturated or aromatic fused ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
- and
- R6 is —R, halogen, —OR, —SR, —N(R′)2, —CN, —NO2, —C(O)R, —CO2R, —C(O)N(R′)2, —C(O)SR, —C(O)C(O)R, —C(O)CH2C(O)R, —C(S)N(R′)2, —C(S)OR, —S(O)R, —SO2R, —SO2N(R′)2, —N(R′)C(O)R, —N(R′)C(O)N(R′)2, —N(R′)SO2R, —N(R′)SO2N(R′)2, —N(R′)N(R′)2, —N(R′)C(═N(R′))N(R′)2, —C═NN(R′)2, —C═NOR, —C(═N(R′))N(R′)2, —OC(O)R, or —OC(O)N(R′)2;
- or:
- R6 and R3 are taken together with their intervening atoms to form an optionally substituted 5-7 membered partially unsaturated or aromatic fused ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
- provided that the compound is other than any one of the following:
20 more elements
A compound selected from the group consisting of:
- or a pharmaceutically acceptable salt thereof.
A composition comprising a compound of formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is —R, halogen, —OR, —SR, —N(R′)2, —CN, —NO2, —C(O)R, —CO2R, —C(O)N(R′)2, —C(O)SR, —C(O)C(O)R, —C(O)CH2C(O)R, —C(S)N(R′)2, —C(S)OR, —S(O)R, —SO2R, —SO2N(R′)2, —N(R′)C(O)R, —N(R′)C(O)N(R′)2, —N(R′)SO2R, —N(R′)SO2N(R′)2, —N(R′)N(R′)2, —N(R′)C(═N(R′))N(R′)2, —C═NN(R′)2, —C═NOR, —C(═N(R′))N(R′)2, —OC(O)R, or —OC(O)N(R′)2;
- each R is independently hydrogen or an optionally substituted group selected from C1 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- each R′ is independently —R, —C(O)R, —CO2R, or two R′ on the same nitrogen are taken together with the intervening nitrogen to form a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
- Ring A is
- R2 and R3 are independently —R, halogen, —OR, —SR, —N(R′)2, —CN, —NO2, —C(O)R, —CO2R, —C(O)N(R′)2, —C(O)SR, —C(O)C(O)R, —C(O)CH2C(O)R, —C(S)N(R′)2, —C(S)OR, —S(O)R, —SO2R, —SO2N(R′)2, —N(R′)C(O)R, —N(R′)C(O)N(R′)2, —N(R′)SO2R, —N(R′)SO2N(R′)2, —N(R′)N(R′)2, —N(R′)C(═N(R′))N(R′)2, —C═NN(R′)2, —C═NOR, —C(═N(R′))N(R′)2, —OC(O)R, or —OC(O)N(R′)2;
- or:
- R2 and R3 are taken together with their intervening atoms to form an optionally substituted 5-7 membered partially unsaturated or aromatic fused ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
- R2′ is —R, —OR, —SR, —N(R′)2, —C(O)R, —CO2R, —C(O)N(R′)2, —C(O)SR, —C(O)C(O)R, —C(O)CH2C(O)R, —C(S)N(R′)2, —C(S)OR, —S(O)R, —SO2R, —SO2N(R′)2, —N(R′)C(O)R, —N(R′)C(O)N(R′)2, —N(R′)SO2R, —N(R′)SO2N(R′)2, —N(R′)N(R′)2, —N(R′)C(═N(R′))N(R′)2, —C═NN(R′)2, —C═NOR, —C(═N(R′))N(R′)2, —OC(O)R, or —OC(O)N(R′)2;
- or:
- R2′ and R3 are taken together with their intervening atoms to form an optionally substituted 5-7 membered partially unsaturated or aromatic fused ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
- X is —N(R4)—, —O—, or —S—;
- R4 is —R, —C(O)R, —CO2R, or —S(O)2R;
- or:
- R4 and R3 are taken together with their intervening atoms to form an optionally substituted 5-7 membered saturated, partially unsaturated, or aromatic fused ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
- R5 is R, —C(O)R, —CO2R, —C(O)N(R′)2, —C(O)C(O)R, or —C(O)CH2C(O)R;
- or:
- R5 and R2 are taken together with their intervening atoms to form an optionally substituted 5-7 membered partially unsaturated or aromatic fused ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
- R6 is —R, halogen, —OR, —SR, —N(R′)2, —CN, —NO2, —C(O)R, —CO2R, —C(O)N(R′)2, —C(O)SR, —C(O)C(O)R, —C(O)CH2C(O)R, —C(S)N(R′)2, —C(S)OR, —S(O)R, —SO2R, —SO2N(R′)2, —N(R′)C(O)R, —N(R′)C(O)N(R′)2, —N(R′)SO2R, —N(R′)SO2N(R′)2, —N(R′)N(R′)2, —N(R′)C(═N(R′))N(R′)2, —C═NN(R′)2, —C═NOR, —C(═N(R′))N(R′)2, —OC(O)R, or —OC(O)N(R′)2;
- or:
- R6 and R3 are taken together with their intervening atoms to form an optionally substituted 5-7 membered partially unsaturated or aromatic fused ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
- and a pharmaceutically acceptable adjuvant, carrier, or vehicle.
19 more elements
Dependencies are inferred from the claim text.