81937-41-9Relevant articles and documents
Structure-Based Optimization of Small Molecule Human Galactokinase Inhibitors
Liu, Li,Tang, Manshu,Pragani, Rajan,Whitby, Frank G.,Zhang, Ya-Qin,Balakrishnan, Bijina,Fang, Yuhong,Karavadhi, Surendra,Tao, Dingyin,LeClair, Christopher A.,Hall, Matthew D.,Marugan, Juan J.,Boxer, Matthew,Shen, Min,Hill, Christopher P.,Lai, Kent,Patnaik, Samarjit
, p. 13551 - 13571 (2021/09/28)
Classic galactosemia is a rare disease caused by inherited deficiency of galactose-1 phosphate uridylyltransferase (GALT). Accumulation of galactose-1 phosphate (gal-1P) is thought to be the major cause of the chronic complications associated with this disease, which currently has no treatment. Inhibiting galactokinase (GALK1), the enzyme that generates galactose-1 phosphate, has been proposed as a novel strategy for treating classic galactosemia. Our previous work identified a highly selective unique dihydropyrimidine inhibitor against GALK1. With the determination of a co-crystal structure of this inhibitor with human GALK1, we initiated a structure-based structure-activity relationship (SAR) optimization campaign that yielded novel analogs with potent biochemical inhibition (IC50 100 nM). Lead compounds were also able to prevent gal-1P accumulation in patient-derived cells at low micromolar concentrations and have pharmacokinetic properties suitable for evaluation in rodent models of galactosemia.
L-Proline as an efficient catalyst for synthesis of N-heterocyclic chalcones as potential antibacterial agents
Bhupathi, Raja S.,Devi, B. Rama,Dubey
experimental part, p. 855 - 859 (2012/08/14)
The condensation of 4-hydroxy-3-acetyl-1H-quinoline-2-one 1 and substitutedbenzaldehydes 2a-i in DMSO solution at room temperature yields quinolone chalcone derivatives 3a-i. L-Proline has been found to be an efficient catalyst for this condensation between 1 and 2. Only 5 mol% of the catalyst is necessary to achieve good yields of the products. Reactions proceed smoothly with variations of the substituents. 1 itself is synthesized by the acylation of commercially available methyl anthranilate 4 with acetoacetic ester 5 in refluxing xylene and subsequent Dieckman intramolcular cyclization of the intermediary 2-methoxycarbonylanilide 6.
4-Hydroxy-2-quinolones. 152*. 3-acetyl-4-hydroxy-2-oxo-1,2- dihydroquinoline and its biologically active derivatives
Ukrainets,Tkach,Yang, Liu Yang
experimental part, p. 169 - 175 (2010/02/27)
A synthesis and study of the spatial structure of 3-acetyl-4-hydroxy-2-oxo- 1,2-dihydroquinoline have been carried. 1-R-4-hydroxy-2-oxo-1,2- dihydroquinoline-3-carboxylic acids [1-(4-hydroxy-2-oxo-1,2-dihydroquinolin-3- yl)ethylidene]hydrazides were prepared from this compound by two routes. A comparative analysis of the antitubercular properties of the synthesized compounds and of the closely structurally related N,N′-di(1-R-4-hydroxy-2- oxo-1,2-dihydroquinoline-3-carbonyl)hydrazines has been performed.