First generation of VFV derivatives. Although log P > 5 and mol wt > 500 are “violations of Lipinski’s rule of five”, there are numerous examples of successful drugs with larger values, especially those aimed at intracellular membrane-bound targets (e.g., cinacalcet/Sensipar at a log P of 6.5 and systemic clinical drug inhibitors of microbial CYP51 such as itraconazole (log P = 6.8, mol wt = 704) and posaconazole (log P = 5.5, mol wt = 701)).