Back to Search
Start Over
Synthesis and biological evaluation of biaryl alkyl ethers as inhibitors of IDO1.
- Source :
-
Bioorganic & Medicinal Chemistry Letters . May2023, Vol. 88, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
-
Abstract
- [Display omitted] Starting from the dialkylaniline indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor lead 3 (IDO1 HeLa IC 50 = 7.0 nM), an iterative process of synthesis and screening led to cyclized analog 21 (IDO1 HeLa IC 50 = 3.6 nM) which maintained the high potency of 3 while addressing issues of lipophilicity, cytochrome P450 (CYP) inhibition, hERG (human potassium ion channel Kv11.1) inhibition, Pregnane X Receptor (PXR) transactivation, and oxidative metabolic stability. An x-ray crystal structure of a biaryl alkyl ether 11 bound to IDO1 was obtained. Consistent with our earlier results, compound 11 was shown to bind to the apo form of the enzyme. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 88
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 163515505
- Full Text :
- https://doi.org/10.1016/j.bmcl.2023.129280