Use of an adaptive study design in single ascending-dose pharmacokinetics of A0001 (α-tocopherylquinone) in healthy male subjects.

A0001 (α-tocopherylquinone) is a potent antioxidant currently in development for the treatment of symptoms associated with inherited mitochondrial disorders. A0001 pharmacokinetics were studied in a single-blind, adaptive design study following a single daily oral dose of placebo (n = 2) or ascending doses of A0001 (n = 8) at 0.25 and 0.

Indanylacetic acids as PPAR-delta activator insulin sensitizers.

A series of indane acetic acid derivatives were prepared which show a spectrum of activity as insulin sensitizers and PPAR-alpha and PPAR-delta ligands. In vivo data are presented for insulin sensitizers with selectivity for PPAR-delta over PPAR-alpha.

Omega-carboxypyridyl substituted ureas as Raf kinase inhibitors: SAR of the amide substituent.

Bis-aryl ureas have been disclosed previously as a potent class of Raf kinase inhibitors. Modifications in the amide portion led to an improvement in aqueous solubility, an important characteristic for an oral drug. Based on this finding, we hypothesize that this portion of the molecule is directed towards the solvent in Raf-1.