24393-13-3Relevant academic research and scientific papers
Structure-aided optimization of non-nucleoside M. tuberculosis thymidylate kinase inhibitors
Song, Lijun,Merceron, Romain,Hulpia, Fabian,Lucía, Ainhoa,Gracia, Bego?a,Jian, Yanlin,Risseeuw, Martijn D.P.,Verstraelen, Toon,Cos, Paul,Aínsa, José A.,Boshoff, Helena I.,Munier-Lehmann, Hélène,Savvides, Savvas N.,Van Calenbergh, Serge
, (2021/08/27)
Mycobacterium tuberculosis thymidylate kinase (MtTMPK) has emerged as an attractive target for rational drug design. We recently investigated new families of non-nucleoside MtTMPK inhibitors in an effort to diversify MtTMPK inhibitor chemical space. We here report a new series of MtTMPK inhibitors by combining the Topliss scheme with rational drug design approaches, fueled by two co-crystal structures of MtTMPK in complex with developed inhibitors. These efforts furnished the most potent MtTMPK inhibitors in our assay, with two analogues displaying low micromolar MIC values against H37Rv Mtb. Prepared inhibitors address new sub-sites in the MtTMPK nucleotide binding pocket, thereby offering new insights into its druggability. We studied the role of efflux pumps as well as the impact of cell wall permeabilizers for selected compounds to potentially provide an explanation for the lack of correlation between potent enzyme inhibition and whole-cell activity.
Studies towards the total synthesis of mumbaistatin: Synthesis of highly substituted benzophenone and anthraquinone building blocks
Kaiser, Florian,Schwink, Lothar,Velder, Janna,Schmalz, Hans-Günther
, p. 3201 - 3217 (2007/10/03)
Model compounds and building blocks for a planned total synthesis of the highly potent glucose-6-phosphate (G6P) translocase inhibitor mumbaistatin (1) and structural analogs were elaborated: compound 1 represents a lead structure in the development of po
An efficient procedure for the preparation of cyclic ketals and thioketals catalyzed by zirconium sulfophenyl phosphonate
Curini,Epifano,Marcotullio,Rosati
, p. 1182 - 1184 (2007/10/03)
A convenient method for the preparation of cyclic ketals and thioketals using zirconium sulfophenyl phosphonate as catalyst is described.
Two practical syntheses of sterically congested benzophenones
Hollinshead,Nichols,Wilson
, p. 6703 - 6709 (2007/10/02)
Two efficient syntheses of the sterically congested tetraortho-substituted benzophenone portion of balanol 1 (a potent PKC inhibitor) in a protected form are described. Ortho lithiation reactions are employed for the preparation of the required 1,2,3-tris
Synthese d'acetals cycliques dans des conditions douces; Applications a l'acetalisation du chloramphenicol
Meslard, J. C.,Subira, F.,Vairon, J. P.,Guy, A.,Garreau, R.
, p. 84 - 89 (2007/10/02)
Acetalization of 1-2 and 1-3 diols, even as sterically crowded as chloramphenicol, by carbonyl derivatives with substituents of various sizes has been performed at room temperature under mild conditions, by using heterogeneous catalysis (sulfonated polystyrene) in the presence of molecular sieves.Several new acetals of chloramphenicol have thus been obtained in good yields, isolated and characterized.
REGIOSELECTIVE METALLATIONS OF (METHOXYMETHOXY)ARENES
Ronald, Robert C.,Winkle, Mark R.
, p. 2031 - 2042 (2007/10/02)
The methoxymethoxy substituent when attached to an aromatic ring functions as a moderately strong ortho-directing group in hydrogen-metal exchenge reactions.In many cases the propensity of the methoxymethoxylated arene toward ring metallations is greatly enhanced with concomitant suppression of undesirable side reactions such as nucleophilic attack and addition of metallating species.Unlike many other ortho-directing groups, the regio-direction of the methoxymethoxy substituent when in conjunction with other weaker directing groups is dependent upon the metallating medium.Thus, by changing the electron donating capacity of the metallating medium it is possible to selectively direct metallation to either of the positions ortho to the methoxymethoxy substituent.
Regioselective Metalation Reactions of Some Substituted (Methoxymethoxy)arenes
Winkle, Mark R.,Ronald, Robert C.
, p. 2101 - 2108 (2007/10/02)
The methoxymethoxy substituent acts as a relatively strong ortho-directing group in hydrogen-metal exchange reactions.However, the directing effects are influenced by the metalation medium, thus permitting an unusual degree of control of the site of metalation.In conjunction with weak ortho-directing groups, the metalation ortho to the methoxymethoxy group can be directed to either of the ortho positions by controlling the electron-donating capacity of the metalating solvent.In strongly donating solvents the 1,2,4-substitution pattern will arise from a meta-substituted methoxymethoxy arene, while in nondonating solvents the 1,2,3-substitution is favored.In addition, the methoxymethoxy group serves also to enhance the rate of metalation and to stabilize the aryl-metalated products so that some competing addition reactions are supressed.
