91067-10-6Relevant academic research and scientific papers
Chemoenzymatic synthesis and biological evaluation of 2- and 3-hydroxypyridine derivatives against Leishmania mexicana
Garcia Linares, Guadalupe,Parraud, Gonzalo,Labriola, Carlos,Baldessari, Alicia
experimental part, p. 4614 - 4624 (2012/09/05)
A series of hydroxyalkyl and acyloxyalkyl derivatives of 2- and 3-hydroxypyridine was synthesized and their biological activity was evaluated as growth inhibitors of protozoan Leishmania mexicana. Thirty novel compounds were obtained through a chemoenzymatic methodology in two reaction steps. The influence of various reaction parameters in the enzymatic step, such as enzyme source, acylating agent/substrate ratio, enzyme/substrate ratio, solvent and temperature, was studied. Some of the evaluated compounds showed a remarkable activity as Leishmania mexicana growth inhibitors, obtaining the best results with the acetylated derivatives. The advantages showed by the enzymatic methodology, such as mild reaction conditions and low environmental impact, make the biocatalysis a convenient way to prepare these derivatives of substituted pyridines with application as potential antiparasitic agents.
Design, synthesis, and biological evaluation of N-Alkylated deoxynojirimycin (DNJ) derivatives for the treatment of dengue virus infection
Yu, Wenquan,Gill, Tina,Wang, Lijuan,Du, Yanming,Ye, Hong,Qu, Xiaowang,Guo, Ju-Tao,Cuconati, Andrea,Zhao, Kang,Block, Timothy M.,Xu, Xiaodong,Chang, Jinhong
supporting information; experimental part, p. 6061 - 6075 (2012/08/14)
We recently described the discovery of oxygenated N-alkyl deoxynojirimycin (DNJ) derivative 7 (CM-10-18) with antiviral activity against dengue virus (DENV) infection both in vitro and in vivo. This imino sugar was promising but had an EC50 against DENV in BHK cells of 6.5 μM, which limited its use in in vivo. Compound 7 presented structural opportunities for activity relationship analysis, which we exploited and report here. These structure-activity relationship studies led to analogues 2h, 2l, 3j, 3l, 3v, and 4b-4c with nanomolar antiviral activity (EC50 = 0.3-0.5 μM) against DENV infection, while maintaining low cytotoxicity (CC50 > 500 μM, SI > 1000). In male Sprague-Dawley rats, compound 3l was well tolerated at a dose up to 200 mg/kg and displayed desirable PK profiles, with significantly improved bioavailability (F = 92 α 4%).
