854645-25-3Relevant academic research and scientific papers
Discovery and preliminary structure–activity relationship of 1H-indazoles with promising indoleamine-2,3-dioxygenase 1 (IDO1) inhibition properties
Qian, Shan,He, Tao,Wang, Wei,He, Yanying,Zhang, Man,Yang, Lingling,Li, Guobo,Wang, Zhouyu
, p. 6194 - 6205 (2016)
Indoleamine 2,3-dioxygenase 1 (IDO1)-mediated kynurenine pathway of tryptophan degradation is identified as an important immune effector pathway in the tumor cells to escape a potentially effective immune response. IDO1 is an attractive target for anticancer therapy and the discovery of IDO1 inhibitors has been intensely ongoing in both academic research laboratories and pharmaceutical organizations. Our study discovered that 1H-indazole was a novel key pharmacophore with potent IDO1 inhibitory activity. A series of new 1H-indazole derivatives were synthesized and determined the enzyme inhibitory activities, and the compound 2g exhibited the highest activity with an IC50value of 5.3 μM. The structure–activity relationships (SARs) analysis of the 1H-indazole derivatives as novel IDO1 inhibitors indicated that the 1H-indazole scaffold is necessary for IDO1 inhibition, and the substituent groups at the both 4-position and 6-position largely affect inhibitory activity. The docking model exhibited that the effective interactions of 1H-indazoles with ferrous ion of heme and key residues of hydrophobic Pocket A and B ensured the IDO1 inhibitory activities. The study suggested that the 1H-indazole was a novel interesting scaffold for IDO inhibition for further development.
Catalytic Halogen Bond Activation in the Benzylic C-H Bond Iodination with Iodohydantoins
Combe, Sascha H.,Hosseini, Abolfazl,Song, Lijuan,Hausmann, Heike,Schreiner, Peter R.
supporting information, p. 6156 - 6159 (2017/11/24)
This letter presents the side-chain iodination of electron-deficient benzylic hydrocarbons at rt using N-hydroxyphthalimide (NHPI) as radical initiator and 1,3-diiodo-5,5-dimethylhydantoin and 3-iodo-1,5,5-trimethylhydantoin (3-ITMH) as iodine source. Addition of a carboxylic acid increased the reactivity due to complex formation with and activation of 3-ITMH by proton transfer and halogen bond formation. No SEAr reactions were observed under the employed reaction conditions. Our method enables convenient product isolation and gives 50-72% yields of isolated products.
