616243-03-9Relevant articles and documents
PHARMACEUTICAL COMPOUNDS
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Page/Page column 54-55, (2010/02/07)
The invention provides a compound for use in the prophylaxis or treatment of a disease state or condition mediated by a p38 MAP kinase such as rheumatoid arthritis and osteoarthritis; the compound being of the general formula (I): wherein U, T, V and W are each a nitrogen atom or a group CR4 provided that no more than three of U, T, V and W are nitrogen atoms; R0 is hydrogen, C1-4 hydrocarbyl, halogen or a group -A-R3; R1 is hydrogen, C1-4 hydrocarbyl or a group -A-R3; provided that only one of R0 and R1 is a group -A-R3; R2 is hydrogen, C1-4 hydrocarbyl or halogen; A is a carbon- or heteroatom-containing linker group having a linking chain length of one or two atoms; R3 is a monocyclic or bicyclic heteroaryl group containing from five to twelve ring members; each group R4 is independently selected from hydrogen, hydroxy, halogen, nitro, cyano, a monocyclic heterocyclic group having up to seven ring members, a group N(R5)2, a group C(O)N(R6)2, a group S02N(R6)2, a group Ra-Rb and a group Y; provided that no more than one group Y is present; Ra is a bond, O, S, SO, S02, NH or N-C1-4 hydrocarbyl; Rb is C1-8 hydrocarbyl optionally interrupted by O, S, SO, SO2, NH or N-C1- 4 hydrocarbyl and optionally substituted by one or more substitutents selected from hydroxy, amino, mono- or di-C1-4 hydrocarbylamino, C1 -4 hydrocarbyloxy, oxo, C1 -4 hydrocarbylthio and halogen; each group R5 is independently selected from hydrogen, C1-4 alkyl, C1-4 acyl and C 1-4 alkylsulphonyl; each group R6 is independently selected from hydrogen and C1-4 hydrocarbyl; Y is a group -N(R7)-C(O)-R8 or -N(R7)_SO2-R8; R7 is hydrogen, C1-4 hydrocarbyl or a group C(O)-R8 or S02-R8; R8 is selected from C1-l0 hydrocarbyl, CI-10hydrocarbylamino, CI-10 hydrocarbylthio, C1-l0 hydrocarbyloxy, and aryl, arylamino, arylthio and aryloxy groups, the aryl moieties of which are carbocyclic or heterocyclic and have from five to twelve ring members, each substituent group R8 being optionally substituted by one or more groups R4 other than Y; or R7 and R8 together with the nitrogen and carbon or sulphur atoms to which they are attached are linked to form a ring structure of 4 to 7 ring members; wherein R0 is other than a 2-(2,4-diamino-6-triazinyl)ethyl group when, in combination, U, T, V and W are all CH, and R1 and R2 are both hydrogen; and provided that when the group -A-R3 contains an acidic substitituent group selected from carboxylic, phosphonic and sulphonic acids and tetrazoles, or contains a -C(O)NSO2- group, or when -A- is -C(O)N- and the nitrogen atom of the group A is linked directly to a furan or thiophene ring, then either R1 is -A-R3 and both R0 and R2 are hydrogen, or R0 is-A-R3 and R1 is hydrogen.
