Table 1.

Thiadiazine analog potencies and early in vitro ADME properties.

^aP. falciparum Dd2 (clone B2) activity in SYBR Green based 72 h in vitro proliferation assay; shown is the AC₅₀ value expressed Log[M] ± SD, of at least three independent assays, then expressed in brackets as approximate value in µM.

^b(-), indicates no activity or efficacy in the assay in the concentration range tested (highest concentrations of 29 µM).

^cInhibition of liver-stage development assay potency, 48 h assay employing a firefly luciferase reporter P. berghei line.

^dMammalian cellular toxicity assessed against HepG2 cells, 48 h compound exposure.

Pharmacokinetic modeling experiments preformed as described previously—^eaqueous solubility⁶⁵.

^fParallel artificial membrane permeability assay (PAMPA)⁶⁴. ND (not detectable), indicates compound not detectable, could reflect insolubility, non-specific binding, compound being stuck in the lipid bi-layer, etc.

^gRat liver microsomal stability (RLMS) in microsomes⁶⁶.