Substituted imidazoles that inhibit cytokine production and are useful in the treatment of inflammatory disease

摘要

Compounds of formula I wherein, R1 is phenyl, substituted phenyl (where the substituents are C1-5alkyl, halogen, nitro, trifluoromethyl, and nitrile), or heteroaryl where the heteroaryl contains 5 to 6 ring atoms; R2 is phenyl, substituted phenyl (where the substituents are C1-5alkyl, halogen, nitro, trifluoromethyl, and nitrile), heteroaryl where the heteroarylcontains 5 to 6 ring atoms and is optionally C1-4alkyl substituted; R3 is hydrogen, SEM, C1-5alkoxycarbonyl, aryloxycarbonyl, arylC1-5alkyloxycarbonyl, arylC1-5aIkyl, substituted arylC1-5alkyl (where the aryl substituents are independently selected from one or more of C1-5alkyl, C1-5alkoxy, halogen, amino, C1-5alkylamino, and diC1-5alkylamino), phthalimidoC1-5alkyl, aminoC1-5alkyl, diaminoC1-5alkyl, succinimidoC1-5alkyl, C1-5alkylcarbonyl, arylcarbonyl, C1-5alkylcarbonylC1-5alkyl, aryloxycarbonylC1-5alkyl, heteroarylC1-5alkyl where the heteroaryl contains 5 to 6 ring atoms; R4 is (A)-(CH2)q-X where: A is vinylene, ethynylene or formula II where, R5 is selected from the group consisting of hydrogen, C1-5alkyl, phenyl and phenylC1-5alkyl; and q is 0-9, and X is as listed in the specification. The pharmaceuticals compositions containing compounds of formula I inhibit the production of a number of inflammatory cytokines (TNF-a and IL-1b), and are useful in treating disease with overproduction of inflammatory cytokines.