RESUMO
D-Alanine-D-alanine ligase (Ddl) catalyzes the biosynthesis of an essential bacterial peptidoglycan precursor D-alanyl-D-alanine and it represents an important target for development of new antibacterial drugs. A series of semicarbazides, aminocarbonyldiazenecarboxylates, diazenedicarboxamides, and hydrazinedicarboxamides was synthesized and screened for inhibition of DdlB from Escherichia coli. Compounds with good inhibitory activity were identified, enabling us to deduce initial structure-activity relationships. Thirteen diazenedicarboxamides were better inhibitors than D-cycloserine and some of them also possess antibacterial activity, which makes them a promising starting point for further development.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Química Farmacêutica/métodos , Imidas/química , Peptídeo Sintases/antagonistas & inibidores , Difosfato de Adenosina/química , Ácidos Carboxílicos/química , Catálise , Cristalografia por Raios X , Ciclosserina/química , Desenho de Fármacos , Escherichia coli/metabolismo , Imidas/farmacologia , Modelos Químicos , Conformação Molecular , FosforilaçãoRESUMO
The electrophilic amination of 2-fluorophenol, 4-fluorophenol, and 2-chlorophenol was observed to occur as a result of their treatment with diazenes 1-4 under mild reaction conditions in the presence of ZrCl(4). The products originating from the 2-fluorophenol or 2-chlorophenol can be considered as "normal" products of amination. On the other hand, the 2-chloro-4-amino-substituted phenols obtained from the 4-fluorophenol seem to be formed in a process that involves an ipso amination, the complete removal of the fluorine atom, and the introduction of the chlorine atom.
RESUMO
An electrophilic amination of halogenated phenols with diisopropyl diazenedicarboxylate in the presence of ZrCl4 as a Lewis acid, accompanied by a halogen migration, was demonstrated for the first time; the fluorine, chlorine, bromine, or iodine atom migrated during the amination process under mild reaction conditions.
