Potency and Selectivity by Introduction of Fluorine

BACE-1 IC5Q= 8 nM BACE-1 IC50 = 4 nM BACE-1 ICjq — 4 nM 

BACE-2 IC50 = 4270 nM BACE-2 IC5o = 785 nM BACE-2 IC50= 177 nM 

Compound R1 R2 ORL1 binding0 IC50 (nM) Antagonism0 IC50 ( nM) pK b N1 N2 Log D7/ Human P-gp transport ratiod 

There are many examples of the introduction of fluorine enhancing on-target activity and these only represent a small number. Many more will be exemplified in the remaining sections of this chapter. 

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