Oxidative metabolism of the trifluoromethoxy moiety of OSI-930.

Cytochrome P450 can catalyze a wide array of remarkable oxidations, including O-dealkylations, which are performed via oxidation of the alpha-carbon of the ether. When C-H bonds are replaced with C-F bonds, however, the bond strength is much greater, and it significantly deters oxidation at the carbon. Another recently elucidated reaction catalyzed by P450, ipso substitution, results in displacement of aromatic ring substituents such as an alkoxy group via hydroxyl substitution.

Safety assessment of 4'-thio-beta-D-arabinofuranosylcytosine in the beagle dog suggests a drug-induced centrally mediated effect on the hypothalamic-pituitary-adrenal axis.

4'-Thio-beta-D-arabinofuranosylcytosine (OSI-7836) is a nucleoside analogue with structural similarity to gemcitabine and cytarabine (ara-C). Myelosuppression, reversible transaminase elevations, and flu-like symptoms are common side effects associated with human use of gemcitabine and ara-C. Fatigue is also associated with the use of gemcitabine and OSI-7836 in humans.