Discovery and preliminary SARs of keto-indoles as novel indoleamine 2,3-dioxygenase (IDO) inhibitors

作者：Dolusic Eduard; Larrieu Pierre; Blanc Sebastien; Sapunaric Frederic; Pouyez Jenny; Moineaux Laurence; Colette Delphine; Stroobant Vincent; Pilotte Luc; Colau Didier; Ferain Thierry; Fraser Graeme; Galleni Moreno; Frere Jean Marie; Masereel Bernard; Van den Eynde Benoit; Wouters Johan; Frederick Raphael^*

来源：European Journal of Medicinal Chemistry, 2011, 46(7): 3058-3065.

DOI：10.1016/j.ejmech.2011.02.049

• Indoleamine 2,3-dioxygenase
• Enzyme inhibitors
• Keto-indoles
• IDO
• Structure-based drug discovery
• Structure-activity relationships

Indoleamine 2,3-dioxygenase (IDO) is an important new therapeutic target for the treatment of cancer. With the aim of discovering novel IDO inhibitors, a virtual screen was undertaken and led to the discovery of the keto-indole derivative 1a endowed with an inhibitory potency in the micromolar range. Detailed kinetics were performed and revealed an uncompetitive inhibition profile. Preliminary SARs were drawn in this series and corroborated the putative binding orientation as suggested by docking.

• 出版日期2011-7