- Chiral resolution, absolute configuration determination, and stereo-activity relationship study of IDO1 inhibitor NLG919
-
NLG919 (1) with two chiral carbon atoms on its chemical structure is a potent indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor. We developed an effective way to prepare all stereoisomers of 1, the key step being the chiral resolution of racemic intermediate 2. The optimal resolution solvent system was identified as dichloromethane and n-pentane or petroleum ether. Using (?)-di-p-toluoyl-D-tartaric acid as resolution reagent, optical pure (R)-2 (e.e. > 99%, yield = 70%) was obtained. The mechanism of chiral resolution was clarified through single-crystal X-ray diffraction of the diastereomeric salt. The absolute configurations of four stereoisomers of 1 were established through electronic circular dichroism spectra, quantum chemical calculation and transition metal method. Their IDO1 inhibitory activity was assessed by pharmacological experiments in vitro and in mouse, demonstrating that S configuration of C5 played an important role on the inhibition of IDO1, while the stereochemistry on C2′ exerted little effect on the IDO1 inhibitory activity in mouse.
- Liu, Wen-Qiang,Lai, Fang-Fang,Zhang, Jie,Sheng, Li,Li, Yan,Li, Li,Chen, Xiao-Guang
-
p. 3045 - 3051
(2018/05/16)
-
- A deuterated of the IDO inhibitor and its preparation and use (by machine translation)
-
The invention provides a deuterated of the IDO inhibitor and its preparation and use, as shown in formula I provide compound or its crystalline form, a pharmaceutically acceptable salt, hydrate or solvate. The preparation of the compound or its crystalline form, a pharmaceutically acceptable salt, hydrate or solvate, can be regarded as the IDO inhibitor, can be used for the treatment of IDO related diseases, in particular cancer, viral infection, depression, neurodegenerative disease, trauma, age-related cataract, organ transplant rejection and autoimmune diseases. (by machine translation)
- -
-
-
- COMPOUNDS FOR THE INHIBITION OF INDOLEAMINE-2,3-DIOXYGENASE
-
The present invention relates to compounds, and pharmaceutically acceptable compositions thereof, useful as antagonists of IDO, and for the treatment of IDO-related disorders.
- -
-
-
- FUSED IMIDAZOLE DERIVATIVES USEFUL AS IDO INHIBITORS
-
Presently provided are IDO inhibitors and pharmaceutical compositions thereof, useful for modulating an activity of indoleamine 2,3-dioxygenase; treating indoleamine 2,3-dioxygenase (IDO) mediated inimunosuppression; treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine-2,3-dioxygenase; enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent; treating tumor-specific immunosuppression associated with cancer; and treating immunosupression associated with an infectious disease.
- -
-
Page/Page column 121
(2012/11/06)
-