81937-41-9Relevant academic research and scientific papers
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.
Structure of the imine 4-hydroxy-2-quinoline ketone compound, and its preparation and use
-
Paragraph 0030; 0031, (2016/10/10)
The invention relates to 4-hydroxy-2-quinolinone compounds containing an imine structure, and preparation and an application thereof. A general formula is represented as the formula (I), wherein meanings of groups in the formula are defined in the specification. The compounds represented by the general formula (I) have quite good herbicidal and fungicidal activities and are widely applied in prevention and treatment of weeds and pathogenic bacteria of crops.
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.
Solvent-free protocol for stereo selective crossed aldol condensation assisted by solid acid catalyst
Bhupathi, Raja S.,Rama Devi,Dubey
experimental part, p. 4215 - 4218 (2012/01/06)
A highly efficient, inexpensive, recyclable, green and solvent free protocol has been developed for crossed-aldol reaction. SiO2-OSO 3H has been found to be an efficient catalyst for the synthesis of 4-hydroxy-3-(3-phenyl-acryloyl)-1H-quinoline-2-one derivatives 3(a-i) from 4-hydroxy-3-acetyl-1H-quinoline-2-one (1) and substituted benzaldehydes 2(a-i). Reactions occurred smoothly with variations of the substituents. The reagent can be reused for five cycles with out sacrificing the yields and activity. This method is simple, convenient and the target compounds are produced in good to excellent yields. Compound 1 can be synthesized by the acylation of methyl anthranilate (4) with acetoacetic ester (5) in refluxing xylene and subsequent Dieckman cyclization of the intermediary 2-methoxycarbonyl anilide (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.
Synthesis of Pyrazole, Quinoline and Quinazoline Derivatives: Part I - Reactions of o-Aminobenzoic Acid Methyl Ester and Its Hydrazide with Ethyl Acetoacetate and Diethyl Malonate
Phadtare, S. K.,Kamat, S. K.,Panse, G. T.
, p. 496 - 498 (2007/10/02)
The reactions of o-aminobenzoic acid methyl ester (I) and its hydrazide (VII) with ethyl acetoacetate (II) and diethyl malonate (VIII) give pyrazole, quinoline and quinazoline derivatives.Mechanisms for their formation have been rationalised.
