| 摘要 |
A series of imidazopyrimidines of Formula (I), and pharmaceutical compositions containing them are described. The compounds described inhibit the production of a number of inflammatory cytokines and are useful in the treatment and prevention of diseases associated with the overproduction thereof, such as rheumatoid arthritis, inflammatory bowel disease, septic shock, osteoporosis, osteoarthritis, neuropathic pain, HIV replication, HIV dementia, viral myocarditis, insulin-dependent diabetes, non-insulin-dependent diabetes, periodontal disease, restenosis, alopecia areta, T-cell depletion in HIV infection or AIDS, psoriasis, acute pancreatitis, allograft rejection, allergic inflammation in the lung, atherosclerosis, multiple sclerosis, cachexia, Alzheimer's disease, stroke, Crohn's disease, ischemia, congestive heart failure, pulmonary fibrosis, hepatitis, glioblastoma, Guillain-Barre Syndrome, and systemic lupus erythematosus. Formula I is depicted, wherein (a) R1 is selected from the group consisting of NH2, C1-5alkylamino, diC1-5alkylamino, hydroxy, C1-5alkoxy, phenylmethylamino, heterocyclylmethyl, C1-5alkylcarbonylamino, and substituted phenylcarbonylamino, wherein the phenylmethylamino and heterocyclylmethyl may be substituted on its phenyl moiety by one or more members selected from the group consisting of halogen, C1-5alkyl, C1-5alkoxy, arylC1-3alkylamino, R'R"NCH=N- and OR"', the R', R" and R"' being independently selected from H, C1-5alkyl, phenylmethyl, substituted phenylmethyl, alpha-alkyl-phenylmethyl, substituted alpha-alkyl-phenylmethyl, heterocyclylmethyl, and substituted heterocyclylmethyl ; (b) Y is selected from the group consisting of H, halogen, heterocycle, OR4, SR4, NR4 and NR4R5, wherein R4 and R5 are independently selected from H, heterocyclyl, C3-5carbocycle, phenyl, alpha-alkyl-phenylC1-5alkyl, straight or branched alkyl optionally substituted with R1 NR1, N(R)2, C3-5carbocycle, phenyl or substituted phenyl, wherein (i) R is H, halogen, C1-5alkyl, phenyl methyl, substituted phenyl methyl, SO2Ph, pyridyl, or pyridylmethyl, and (ii) the phenyl, heterocyclyi, and alpha-alkyl-phenylC1-5alkyl may be substituted by one or more members selected from the group consisting of halogen, C1-5alkyl, C1-5alkoxy, aryIC1-3alkylamino, phenyl methyl, substituted phenyl methyl, R'R"NCH=N-and OR"' as defined in (a) above; (c) R2 is one to five members independently selected from the group consisting of halogen, trifluoromethyl, -NCH2PH, C1-5alkyl, and C1-5alkoxy; (d) R3 is H or, taken together, an aromatic ring; and (e) X is N or CH.
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