Methoxyoxalamido chemistry in the synthesis of tethered phosphoramidites and functionalized oligonucleotides.

A general approach to phosphoramidites tethered with single and multiple linkers through the use of methoxyoxalamido (MOX) chemistry is described. The approach utilizes readily available and inexpensive primary aliphatic amino alcohols and diamines to produce a rich and diverse variety of tethered phosphoramidites. Furthermore, the use of MOX chemistry in a modular fashion enables fairly rapid assembly of compound tethers.

Characterization of human cytochrome P450 enzymes catalyzing domperidone N-dealkylation and hydroxylation in vitro.

Aims: To confirm the identity of the major metabolites of domperidone and to characterize the cytochrome P450s (CYPs) involved in their formation.

Methods: Human liver microsomes (HLMs) were used to characterize the kinetics of domperidone metabolism and liquid chromatography-mass spectrometry to identify the products. Isoform-specific chemical inhibitors, correlation analysis and expressed human CYP genes were used to identify the CYPs involved in domperidone oxidation.

Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine.

Background: Tamoxifen, a selective estrogen receptor modulator (SERM), is converted to 4-hydroxy-tamoxifen and other active metabolites by cytochrome P450 (CYP) enzymes. Selective serotonin reuptake inhibitors (SSRIs), which are often prescribed to alleviate tamoxifen-associated hot flashes, can inhibit CYPs. In a prospective clinical trial, we tested the effects of coadministration of tamoxifen and the SSRI paroxetine, an inhibitor of CYP2D6, on tamoxifen metabolism.