791070-91-2Relevant academic research and scientific papers
Identification and Optimization of a Series of 8-Hydroxy Naphthyridines with Potent in Vitro Antileishmanial Activity: Initial SAR and Assessment of in Vivo Activity
Thomas, Michael G.,De Rycker, Manu,Wall, Richard J.,Spinks, Daniel,Epemolu, Ola,Manthri, Sujatha,Norval, Suzanne,Osuna-Cabello, Maria,Patterson, Stephen,Riley, Jennifer,Simeons, Frederick R. C.,Stojanovski, Laste,Thomas, John,Thompson, Stephen,Naylor, Claire,Fiandor, Jose M.,Wyatt, Paul G.,Marco, Maria,Wyllie, Susan,Read, Kevin D.,Miles, Timothy J.,Gilbert, Ian H.
, p. 9523 - 9539 (2020/10/19)
Visceral leishmaniasis (VL) is a parasitic infection that results in approximately 26 ?000-65 ?000 deaths annually. The available treatments are hampered by issues such as toxicity, variable efficacy, and unsuitable dosing options. The need for new treatments is urgent and led to a collaboration between the Drugs for Neglected Diseases initiative (DNDi), GlaxoSmithKline (GSK), and the University of Dundee. An 8-hydroxynaphthyridine was identified as a start point, and an early compound demonstrated weak efficacy in a mouse model of VL but was hampered by glucuronidation. Efforts to address this led to the development of compounds with improved in vitro profiles, but these were poorly tolerated in vivo. Investigation of the mode of action (MoA) demonstrated that activity was driven by sequestration of divalent metal cations, a mechanism which was likely to drive the poor tolerability. This highlights the importance of investigating MoA and pharmacokinetics at an early stage for phenotypically active series.
Tandem retro-Michael addition-Claisen rearrangement-intramolecular cyclization: One-pot synthesis of densely functionalized ethyl dihydropyrimidine-4-carboxylates from simple building blocks
Naidu, B. Narasimhulu
, p. 547 - 550 (2008/12/21)
Pyrolysis of suitably functionalized oxadiazoline diesters in refluxing xylenes provided ethyl 1,2-disubstituted 5-hydroxy-6-oxo-1,6-dihydropyrimidine- 4-carboxylates in moderate to good yields. Under thermal conditions, the oxadiazoline esters undergo a sequence of complex molecular reorganizations, namely retro-Michael addition, Claisen rearrangement, and cyclization, to produce the desired pyrimidinones. Georg Thieme Verlag Stuttgart.
Facile one-Pot synthesis of 2,3,5-substituted 1,2,4-oxadiazolines from nitriles in aqueous solution
Naidu, B. Narasimhulu,Sorenson, Margaret E.
, p. 1391 - 1393 (2007/10/03)
(Chemical Equation Presented) Alkyl/aryl amidoximes, prepared from the corresponding nitriles and N-alkylhydroxylamines, have readily undergone consecutive Michael additions to electron-deficient alkynes and provided highly substituted 1,2,4-oxadiazolines
