| 摘要 |
Methods for treating a disease or disorder selected from pain, cancer, inflammation, neurodegenerative disease, Typanosoma cruzi infection and osteolytic disease in a mammal, which comprise administering to said mammal a therapeutically effective amount of a compound of Formula I;
in which R1, R2, R3, R4, X, Y and n have the meanings given in the specification. |
| 主权项 |
1. A method for inhibiting a Trk kinase in a cell, the method comprising contacting the cell with an effective amount of a compound of Formula Ior a pharmaceutically acceptable salt thereof, wherein:
R1 is H or (1-6C alkyl); R2 is NRbRc, (1-4C)alkyl, (1-4C)fluoroalkyl, CF3, (1-4C)hydroxyalkyl, -(1-4C alkyl)hetAr1, -(1-4C alkyl)NH(1-4C alkyl), hetAr2, hetCyc1, hetCyc2, phenyl which is optionally substituted with NHSO2(1-4C alkyl), or (3-6C)cycloalkyl which is optionally substituted with (1-4C alkyl), CN, OH, CF3, CO2(1-4C alkyl) or CO2H; Rb is H or (1-6C alkyl); Rc is H, (1-4C)alkyl, (1-4C)hydroxyalkyl, hetAr3, or phenyl, wherein said phenyl is optionally substituted with one or more substituents independently selected from halogen, CN, CF3 and —O(1-4C alkyl), or NRbRc forms a 4 membered heterocyclic ring having a ring nitrogen atom, wherein said heterocyclic ring is optionally substituted with one or more substituents independently selected from halogen, OH, (1-4C alkyl), (1-4 C)alkoxy, —OC(═O)(1-4C alkyl), NH2, —NHC(═O)O(1-4C alkyl), and (1-4C)hydroxyalkyl, or NRbRc forms a 5-6 membered heterocyclic ring having a ring heteroatom which is nitrogen and optionally having a second ring heteroatom or group selected from N, O and SO2, wherein the heterocyclic ring is optionally substituted with one or more substituents independently selected from OH, halogen, CF3, (1-4C)alkyl, CO2(1-4C alkyl), CO2H, NH2, NHC(═O)O(1-4C alkyl) and oxo, or NRbRc forms a 7-8 membered bridged heterocyclic ring having 1-2 ring nitrogen atoms and optionally substituted with CO2(1-4C alkyl); hetAr1 is a 5-membered heteroaryl ring having 1-3 ring nitrogen atoms; hetAr2 is 5-6 membered heteroaryl ring having at least one nitrogen ring atom and optionally having a second ring heteroatom independently selected from N and S, wherein said heteroaryl ring is optionally substituted with one or more substituents independently selected from (1-4C alkyl), halogen, -(1-4 C)alkoxy, and NH(1-4C alkyl); hetCyc1 is a carbon-linked 4-6 membered azacyclic ring optionally substituted with one or more substituents independently selected from (1-4C alkyl), CO2H and CO2(1-4C alkyl); hetCyc2 is a pyridinone or pyridazinone ring substituted with a substituent selected from (1-4C)alkyl; hetAr3 is a 5-6 membered heteroaryl ring having 1-2 ring heteroatoms independently selected from N and O and optionally substituted with one or more substituents independently selected from (1-4C)alkyl; Y is a phenyl ring optionally substituted with one or more substituents independently selected from halogen, (1-4C)alkoxy, CF3 and CHF2, or a 5-6 membered heteroaryl ring having a ring heteroatom selected from N and S; X is null, —CH2—, —CH2CH2—, —CH2O—, or —CH2NRd— Rd is H or (1-4C alkyl); R3 is H or (1-4C alkyl); each R4 is independently selected from halogen, (1-4C)alkyl, OH, (1-4 C)alkoxy, NH2, NH(1-4C alkyl) and CH2OH; and n is 0, 1, 2, 3, 4, 5 or 6. |
