5-Amino-2-carbonylthiophene derivatives for use as p38 MAPK inhibitors in the treatment of inflammatory diseases

摘要

This recent patent application from Astex (WO2004089929) describes p38 inhibitors containing uncyclised amides or ureas. Other urea and amide inhibitors of p38 are in the prior art. The present invention is based on the substitution pattern on a thiophene scaffold to which the amides and ureas are attached. An earlier patent application from Astex (WO2004004720) describes p38 inhibitors in which the generic structures do not require amides or ureas. However, the earlier patent application provides some structure-activity relationships (SARs) in which the most potent analogues are amides or ureas. Common structural features are apparent for the likely potent acyclic amide and ureas in the two Astex patent applications. These features may also connect the functionality in the Astex compounds to similar structures in competitor acyclic amide and urea p38 inhibitors. Crystallography data on two series of competitor acyclic urea and amide analogues have been reported.