173152-99-3Relevant articles and documents
Direct room-temperature lactonisation of alcohols and ethers onto amides: An "amide strategy" for synthesis
Valerio, Viviana,Petkova, Desislava,Madelaine, Claire,Maulide, Nuno
, p. 2606 - 2610 (2013/03/14)
Last-minute deal: A direct lactonisation of ethers and alcohols onto amides that proceeds at room temperature under mild conditions is reported (see scheme). This allows the effective saving of up to two unproductive, sequential deprotection operations in synthetic sequences. Mechanistic studies are described, and a new "amide strategy" that exploits the dual robustness/late-stage selective activation properties of this functional group is outlined. Copyright
New Antibacterial Agents Derived from the DNA Gyrase Inhibitor Cyclothialidine
Angehrn, Peter,Buchmann, Stefan,Funk, Christoph,Goetschi, Erwin,Gmuender, Hans,Hebeisen, Paul,Kostrewa, Dirk,Link, Helmut,Luebbers, Thomas,Masciadri, Raffaello,Nielsen, Joergen,Reindl, Peter,Ricklin, Fabienne,Schmitt-Hoffmann, Anne,Theil, Frank-Peter
, p. 1487 - 1513 (2007/10/03)
Cyclothialidine (1, Ro 09-1437) is a potent DNA gyrase inhibitor that was isolated from Streptomyces filipinensis NR0484 and is a member of a new family of natural products. It acts by competitively inhibiting the ATPase activity exerted by the B subunit of DNA gyrase but barely exhibits any growth inhibitory activity against intact bacterial cells, presumably due to insufficient permeation of the cytoplasmic membrane. To explore the antibacterial potential of 1, we developed a flexible synthetic route allowing for the systematic modification of its structure. From a first set of analogues, structure-activity relationships (SAR) were established for different substitution patterns, and the 14-hydroxylated, bicyclic core (X) of 1 seemed to be the structural prerequisite for DNA gyrase inhibitory activity. The variation of the lactone ring size, however, revealed that activity can be found among 11- to 16-membered lactones, and even seco-analogues were shown to maintain some enzyme inhibitory properties, thereby reducing the minimal structural requirements to a rather simple, hydroxylated benzyl sulfide (XI). On the basis of these "minimal structures" a modification program afforded a number of inhibitors that showed in vitro activity against Gram-positive bacteria. The best activities were displayed by 14-membered lactones, and representatives of this subclass exhibit excellent and broad in vitro antibacterial activity against Gram-positive pathogens, including Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus faecalis, and overcome resistance against clinically used drugs. By improving the pharmacokinetic properties of the most active compounds (94, 97), in particular by lowering their lipophilic properties, we were able to identify congeners of cyclothialidine (1) that showed efficacy in vivo.
Mono- and bicyclic DNA gyrase inhibitors
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, (2008/06/13)
The present invention relates to a compound of the formula STR1 wherein X1, R1, R2, OP, R3, R4, R5, R6, and R0 are as described herein, and their pharmaceutically acceptable salts thereof carrying an acidic and/or basic substituent. The compound of formula I as well as their pharmaceutically acceptable salts inhibit DNA gyrase activity in bacteria and possess antibiotic, especially antibacterial activity against microorganisms and can be used in the control or prevention of infectious diseases.
