Table 2. Exploration of Novel Spirocyclic Cores.

^aBiochemical inhibition of PLD1/2 was determined by immunoprecipitation on a plate (IPoP) of PLD1/2 from HEK cells.

^bCellular assay performed with Calu-1 cell line.

^cIntrinsic CL (Cl_int) in rat or human liver microsomes.

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

^eKinetic solubility pH = 6.8.

^fClearance determined by cassette dosing; Clu = unbound in vivo clearance (Cl/fu).