Document Report Card
Basic Information
ID: ALA1777746
Journal: Bioorg Med Chem Lett
Title: 1,5-Substituted nipecotic amides: selective PDE8 inhibitors displaying diastereomer-dependent microsomal stability.
Authors: DeNinno MP, Wright SW, Visser MS, Etienne JB, Moore DE, Olson TV, Rocke BN, Andrews MP, Zarbo C, Millham ML, Boscoe BP, Boyer DD, Doran SD, Houseknecht KL.
Abstract: The first highly potent and selective PDE8 inhibitors are disclosed. The initial tetrahydroisoquinoline hit was transformed into a nipecotic amide series in order to address a reactive metabolite issue. Reduction of lipophilicity to address metabolic liabilities uncovered an interesting diastereomer-dependent trend in turnover by human microsomes.
CiteXplore: 21459572