Lead compounds privileged structures

Historically, the strategies pursued in the discovery of Kvl.5 inhibitor lead compounds have varied chemistry utilizing potassium channel modulator privileged structures as cores or scaffolds, as previously reviewed [34] rescaffolding of disclosed chemical series [41,54,56] and pharmacophore... 

The protein superfamily of proteases [78, 79], however, is an ideal framework for a directed privileged structure-based masterkey concept. It has already been reported that the 5,5-trans-fused lactam moiety was systematically optimized and explored as a serine protease-directed scaffold by GlaxoSmithKline and has delivered progressible lead compounds for various members of that target class [3], such as thrombin [80, 81], elastase [82, 83], HCMV protease [84, 85], and the hepatitis C virus-encoded NS3-4A protease [86, 87]. Here, the initially identified scaffold was engineered toward the serine protease-wide commonality in substrate binding and processing [3],... 

This approach is based on the chiral dihydronaphthalene motif, represented by compound (f )-8. Generally, this motif is found in a number of biologically active molecules and therefore it is a chemically privileged structure in the sense of being a starting point for the identification of a lead compound for evaluation [30]. 

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