Fused Heterocyclic Compounds as Potent Indoleamine-2,3-dioxygenase 1 Inhibitors.

ABSTRACT: Uncontrolled metabolism of l-tryptophan (l-Trp) in the immune system has been recognized as a critical cellular process in immune tolerance. Indoleamine 2,3-dioxygenase 1 (IDO1) enzyme plays an important role in the metabolism of a local l-Trp through the kynurenine pathway in the immune systems. In this regard, IDO1 has emerged as a therapeutic target for the treatment of diseases that are associated with immune suppression like chronic infections, cancer, and others. In this study, we synthesized a series of pyridopyrimidine, pyrazolopyranopyrimidine, and dipyrazolopyran derivatives. Further lead optimizations directed to the identification of potent compounds, 4j and 4l (IC₅₀ = 260 and 151 nM, respectively). These compounds also exhibited IDO1 inhibitory activit

SUBMITTER: Panda S 

PROVIDER: S-EPMC5150662 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature