Table 3. Bridged Bicyclic Amine and Exocyclic Amine Replacements for the Azepane Linker.

^ak_inact/K_i values were determined using the nonphosphorylated BTK protein in a continuous-read kinetic enzyme assay, with the mean value for replicates shown in parentheses.

^bMean IC₅₀ values for the inhibition of CD69 expression on CD19+ B cells in human whole blood upon stimulation with anti-IgD.

^cMean IC₅₀ for the inhibition of TMD8 B cell proliferation.

^dMetabolic stability in rat and human liver microsomes (Intrinsic Clearance (Cl_int)).

^eEfflux ratio = P_app(B – A)/P_app(A – B) MDCK-MDR1.

^fFree unbound brain-to-plasma ratio as determined in a 24 h IV infusion rat PK study.

^gIn vitro reactivity assessment using a GSH conjugation assay.