Inhibition of the tissue factor/factor VIIa complex - Lead optimisation using combinatorial chemistry

Article abstract of DOI:10.1016/S0040-4020(99)00266-5

Following a high throughput screen (HTS) for the inhibition of the tissue factor/factor VIIa complex and the identification of a number of original hits a lead optimisation programme was initiated to improve their potency. This necessitated the development of an amidine based linker which allowed the generation of a library of amidinonaphthols prepared both by multiple parallel synthesis (MPS) and split and mix methods. The most active compound had an IC₅₀ of 4μM some 10x more potent than the original lead compound.