Publications by authors named "Ronald Scott Obach"
Article Synopsis
- The first generation 5HT-4 partial agonist, PF-4995274 (TBPT), was found to metabolize into active compounds, M1 and M2, with M2 being predominant in human plasma despite being minor in vitro.
- To minimize metabolism via the piperidine ring, researchers synthesized various heterocyclic replacements like azetidines and pyrrolidines, aiming to preserve drug efficacy while reducing turnover in human liver cells.
- Ultimately, azetidines emerged as effective second-generation 5HT partial agonists, demonstrating a shift in metabolic pathways that avoided problematic metabolites compared to previous drug designs.
Strategies for a comprehensive understanding of metabolism by aldehyde oxidase.
Expert Opin Drug Metab Toxicol
February 2013
Introduction: Aldehyde oxidase (AO) is a drug-metabolizing molybdo-flavoenzyme with profound species differences in expression and activity toward various substrates. The contribution of this enzyme to the metabolism and clearance of heterocyclic-containing xenobiotics appears to have increased in recent years, but has not always been identified prior to clinical studies. As a result, drug candidates have been negatively impacted in development.
View Article and Find Full Text PDF