Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1369118 | Bioorganic & Medicinal Chemistry Letters | 2015 | 6 Pages |
Abstract
Early lead compounds in this gamma secretase modulator series were found to potently inhibit CYP3A4 and other human CYP isoforms increasing their risk of causing drug–drug-interactions (DDIs). Using structure–activity relationships and CYP3A4 structural information, analogs were developed that minimized this DDI potential. Three of these new analogs were further characterized by rat PK, rat PK/PD and rat exploratory toxicity studies resulting in selection of SPI-1865 (14) as a preclinical development candidate.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Jed L. Hubbs, Nathan O. Fuller, Wesley F. Austin, Ruichao Shen, Jianguo Ma, Zhen Gong, Jian Li, Timothy D. McKee, Robyn M.B. Loureiro, Barbara Tate, Jo Ann Dumin, Jeffrey Ives, Brian S. Bronk,