| 摘要 |
The invention is directed to compounds of Formula I:;;wherein Z, X, J, R2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase. Methods of treating autoimmune diseases; and diseases with an inflammatory component; treating metastasis from ovarian cancer, uterine cancer, breast cancer, prostate cancer, lung cancer, colon cancer, stomach cancer, hairy cell leukemia; and treating pain, including skeletal pain caused by tumor metastasis or osteoarthritis, or visceral, inflammatory, and neurogenic pain; as well as osteoporosis, Paget's disease, and other diseases in which bone resorption mediates morbidity including rheumatoid arthritis, and other forms of inflammatory arthritis, osteoarthritis, prosthesis failure, osteolytic sarcoma, myeloma, and tumor metastasis to bone with the compounds of Formula I, are also provided. |
| 主权项 |
1. A compound of Formula I or a solvate, hydrate, tautomer or pharmaceutically acceptable salt thereof, wherein: W is wherein each R4 is independently H, F, Cl, Br, I, OH, OCH3, OCH2CH3, SC(1-4)alkyl, SOC(1-4)alkyl, SO2C(1-4)alkyl, —C(1-3)alkyl, CO2Rd, CONReRf, C≡CRg, or CN;
wherein Rd is H, or —C(1-3)alkyl;
Re is H, or —C(1-3)alkyl;Rf is H, or —C(1-3)alkyl; andRg is H, —CH2OH, or —CH2CH2OH; R2 is cycloalkyl, spiro-substituted cycloalkenyl, heterocyclyl, spirosubstituted piperidinyl, thiophenyl, dihydrosulfonopyranyl, phenyl, furanyl, tetrahydropyridyl, or dihydropyranyl, any of which may be independently substituted with one or two of each of the following: chloro, fluoro, hydroxy, C(1-3)alkyl, and C(1-4)alkyl; Z is H, F, or CH3; J is CH, or N; X is R5 is H, —OC(1-4)alkyl, —CN, —NA3A4, —SO2CH3, —CO2C(1-4)alkyl, —CH2—NA3A4, —CH2CH2NA3A4, —CONA3A4, —CH2OC(1-4)alkyl, —OC(1-4)alkylORa, —NHCH2CH2CO2C(1-4)alkyl, —NHCH2CH2OC(1-4)alkyl, —N(C(1-4)alkyl)CH2CH2NA3A4, —OC(1-4)alkylNA3A4, —OCH2CO2C(1-4)alkyl, —CH2CO2C(1-4)alkyl, —CH2CH2SO2C(1-4)alkyl, —SO2CH2CH2NA3A4, —SOCH2CH2NA3A4, —SCH2CH2NA3A4, —NHSO2CH2CH2NA3A4, phenyl, imidazolyl, thiazolyl, 4H-[1,2,4]oxadiazol-5-onyl, 4H-pyrrolo[2,3-b]pyrazinyl, pyridinyl, [1,3,4]oxadiazolyl, 4H-[1,2,4]triazolyl, tetrazolyl, pyrazolyl, [1,3,5]triazinyl, and [1,3,4]thiadiazolyl; A3 is —C(1-4)alkyl, or CH2CH2ORa; A4 is —C(1-4)alkyl, CORa, CH2CON(CH3)2, —CH2CH2ORa, —CH2CH2SC(1-4)alkyl, —CH2CH2SOC(1-4)alkyl, or —CH2CH2SO2C(1-4)alkyl;
alternatively, A3 and A4 may be taken together to form a nitrogen containing heterocyclic ring selected from the following: wherein Ra is H or C(1-4)alkyl;Raa is H or C(1-4)alkyl; and Rbb is H, —CH2CH2OCH2CH2OCH3, —CH2CO2H, —C(O)C(1-4)alkyl; or CH2C(O)C(1-4)alkyl. |
