1402838-70-3Relevant articles and documents
Discovery of clinical candidate (1 R,4 r)-4-((R)-2-((S)-6-Fluoro-5 H-imidazo[5,1-A[isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol (Navoximod), a potent and selective inhibitor of indoleamine 2,3-dioxygenase 1
Kumar, Sanjeev,Waldo, Jesse P.,Jaipuri, Firoz A.,Marcinowicz, Agnieszka,Van Allen, Clarissa,Adams, James,Kesharwani, Tanay,Zhang, Xiaoxia,Metz, Richard,Oh, Angela J.,Harris, Seth F.,Mautino, Mario R.
, p. 6705 - 6733 (2019/08/20)
A novel class of 5-substituted 5H-imidazo[5,1-a]isoindoles are described as potent inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1). A structure-based drug design approach was used to elaborate the 5H-imidazo[5,1-a]isoindole core and to improve potency and pharmacological properties. Suitably placed hydrophobic and polar functional groups in the lead molecule allowed improvement of IDO1 inhibitory activity while minimizing off-target liabilities. Structure-activity relationship studies focused on optimizing IDO1 inhibition potency and a pharmacokinetic profile amenable to oral dosing while controlling CYP450 and hERG inhibitory properties.
