166411-50-3Relevant articles and documents
Synthesis and Pharmacokinetic Evaluation of Siderophore Biosynthesis Inhibitors for Mycobacterium tuberculosis
Nelson, Kathryn M.,Viswanathan, Kishore,Dawadi, Surendra,Duckworth, Benjamin P.,Boshoff, Helena I.,Barry, Clifton E.,Aldrich, Courtney C.
, p. 5459 - 5475 (2015/08/03)
MbtA catalyzes the first committed biosynthetic step of the mycobactins, which are important virulence factors associated with iron acquisition in Mycobacterium tuberculosis. MbtA is a validated therapeutic target for antitubercular drug development. 5′-O-[N-(Salicyl)sulfamoyl]adenosine (1) is a bisubstrate inhibitor of MbtA and exhibits exceptionally potent biochemical and antitubercular activity. However, 1 suffers from suboptimal drug disposition properties resulting in a short half-life (t1/2), low exposure (AUC), and low bioavailability (F). Four strategies were pursued to address these liabilities including the synthesis of prodrugs, increasing the pKa of the acyl-sulfonyl moiety, modulation of the lipophilicity, and strategic introduction of fluorine into 1. Complete pharmacokinetic (PK) analysis of all compounds was performed. The most successful modifications involved fluorination of the nucleoside that provided substantial improvements in t1/2 and AUC. Increasing the pKa of the acyl-sulfonyl linker yielded incremental enhancements, while modulation of the lipophilicity and prodrug approaches led to substantially poorer PK parameters.
A concise synthesis of anti-viral agent F-ddA, starting from (S)-dihydro-5-(hydroxymethyl)-2(3H)-furanone
Choudhury, Anusuya,Jin, Fuqiang,Wang, Dengjin,Wang, Zhe,Xu, Guoyou,Nguyen, Dieu,Castoro, John,Pierce, Michael E.,Confalone, Pat N.
, p. 247 - 250 (2007/10/03)
Anti-HIV agent β-F-ddA (1) has been synthesized starting from readily available non-sugar, (S)-(+)-Dihydro-5-(hydroxymethyl)-2-(3H)-furanone (4). A highly syn-stereoselective fluorination of the hydroxy lactone 2 generates the key intermediate fluorolactone 5 in a short and concise synthetic sequence. Reduction of 5 followed by bromination generates the aglycon which is glycosylated to generate F-ddA by amination and deprotection. Steric bulk of the 5-protecting group has minimal effect on the steric course of glycosylation.
Convenient synthesis of fluorinated nucleosides with perfluoroalkanesulfonyl fluorides
Takamatsu, Satoshi,Katayama, Satoshi,Hirose, Naoko,De Cock, Etienne,Schelkens, Geert,Demillequand, Marc,Brepoels, Jozef,Izawa, Kunisuke
, p. 849 - 861 (2007/10/03)
Perfluoroalkanesulfonyl fluorides are effective dehydroxy-fluorination agents for the hydroxyl group at the sugar moiety of nucleoside derivatives and give the corresponding fluorinated nucleosides in good yield with an inversion of configuration in a sin