DERIVATIVES OF 4-AMINO-PYRIDINE AS SELECTIVE THROMBIN INHIBITORS

During screening for novel thrombin inhibitors it was discovered that the 4-aminopyridine derivative 1 inhibits human α-thrombin competitively and selectively. The 4-aminopyridine moiety itself is most likely the major determinant of the selectivity due to the increased hydrophobicity of the S1 pocket in thrombin compared to trypsin and plasmin. Optimization led to the selective thrombin inhibitor 14 with an inhibition constant, Ki of 70 nM. © 1997 Elsevier Science Ltd.