55309-53-0Relevant academic research and scientific papers
X-ray Structure-Guided Discovery of a Potent, Orally Bioavailable, Dual Human Indoleamine/Tryptophan 2,3-Dioxygenase (hIDO/hTDO) Inhibitor That Shows Activity in a Mouse Model of Parkinson’s Disease
Ning, Xiang-Li,Li, Yu-Zhi,Huo, Cui,Deng, Ji,Gao, Cheng,Zhu, Kai-Rong,Wang, Miao,Wu, Yu-Xiang,Yu, Jun-Lin,Ren, Ya-Li,Luo, Zong-Yuan,Li, Gen,Chen, Yang,Wang, Si-Yao,Peng, Cheng,Yang, Ling-Ling,Wang, Zhou-Yu,Wu, Yong,Qian, Shan,Li, Guo-Bo
supporting information, p. 8303 - 8332 (2021/06/30)
Human indoleamine 2,3-dioxygenase 1 (hIDO1) and tryptophan 2,3-dioxygenase (hTDO) have been closely linked to the pathogenesis of Parkinson’s disease (PD); nevertheless, development of dual hIDO1 and hTDO inhibitors to evaluate their potential efficacy against PD is still lacking. Here, we report biochemical, biophysical, and computational analyses revealing that 1H-indazole-4-amines inhibit both hIDO1 and hTDO by a mechanism involving direct coordination with the heme ferrous and ferric states. Crystal structure-guided optimization led to23, which manifested IC50values of 0.64 and 0.04 μM to hIDO1 and hTDO, respectively, and had good pharmacokinetic properties and brain penetration in mice.23showed efficacy against the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse motor coordination deficits, comparable to Madopar, an anti-PD medicine. Further studies revealed that different from Madopar,23likely has specific anti-PD mechanisms involving lowering IDO1 expression, alleviating dopaminergic neurodegeneration, reducing inflammatory cytokines and quinolinic acid in mouse brain, and increasing kynurenic acid in mouse blood.
Direct catalytic asymmetric enolexo aldolizations
Pidathala, Chandrakala,Hoang, Linh,Vignola, Nicola,List, Benjamin
, p. 2785 - 2788 (2007/10/03)
32 years after the first, and still the only, catalytic asymmetric intramolecular aldol reaction was published in this journal, the proline-catalyzed Hajos-Parrish-Eder-Sauer-Wiechert reaction is extended for the first time to catalytic asymmetric enolexo
Hydroformylation of epoxides catalyzed by cobalt and hemilabile P-O ligands
Weber,Englert,Ganter,Keim,Moethrath
, p. 1419 - 1420 (2007/10/03)
Complexes of cobalt efficiently catalyze the hydroformylation of epoxides in the presence of hemilabile P-O chelating ligands to give β-hydroxyaldehydes in high selectivities and yields.
