01540nas a2200253   4500000000100000008004100001260001300042653001200055653002900067653002100096653003200117653001100149653001200160653001800172653002900190653003500219653001700254100001500271245012100286300001000407490000600417520084900423022001401272       1993                            d  c1993 Dec10aDapsone10aDihydropteroate Synthase10aEscherichia coli10aEscherichia coli Infections10aHumans10aleprosy10aMycobacterium10aMycobacterium Infections10aTetrahydrofolate Dehydrogenase10aTrimethoprim1 aSeydel J K00aIn vitro and in vivo results of brodimoprim and analogues alone and in combination against E. coli and mycobacteria.  a422-90 v53 a<p>New diaminodiphenylsulfone inhibitors of dihydropteroate synthase are described with increased inhibitory activity against mycobacteria and plasmodia, whereas their side effect of methemoglobin formation could be suppressed. The optimization of diaminobenzylpyrimidines, inhibitors of dihydrofolate reductase, led to derivatives with increased inhibitory effect against mycobacteria, especially M. leprae and plasmodia. Some of these derivatives show autosynergism. Finally the combination of brodimoprim (BDP) and dapsone (DDS) was developed for the treatment of leprosy. First clinical trials in Paraguay and Ethiopia show that combinations of BDP/DDS and BDP/DDS plus rifampicin were highly effective and may become an alternative multi-drug therapy for the treatment of leprosy. The tolerance of the regimens used was generally good.</p>  a1120-009X