Mouse Pharmacokinetic Studies. Studies were conducted by Pharmaron. Fed male CD1 mice (sourced from Si Bei Fu LaboratoryAnimal Technology Co. Ltd.), approximately 6-8 weeks of age and weight of approximately 25-30 g, were dosed with compounds 1, 15 and 58. The formulation for 58 was 5% NMP, 20% PEG 300, 75% "solutol HS 15 in water (15 wt%)" and the dosing concentration was 2.5, 1, 3 mg/mL for the 5, 10 , 30 mpk IV, PO and IP experiments at dosing volume 2, 10 and 10 mL/kg respectively. The formulation for compounds 1 and 15 was PEG300 / 30% solutol in water / Saline (30/17/54) as 1, 1, 3 mg/mL for the 5, 10, 30 mpk doses. Formulated drug samples were prepared prior to dosing a cohort of N=3 mice in each arm. 25 L of blood was collected from the dorsal metatarsal vein by serial bleeding. Blood samples were then transferred into plastic microcentrifuge tubes containing heparin-Na as anticoagulant. Samples were then centrifuged at 4000g for 5 min at 4°C to obtain plasma. Plasma samples were then stored in polypropylene tubes, quickly frozen, and kept at-75°C until analyzed by LC/MS/MS. Animals were also monitored during the in-life phase by once daily cageside observations; no adverse clinical signs were noted as part of the PK report.