18620-73-0Relevant articles and documents
Folate-Synthesizing Enzyme System as Target for Development of Inhibitors and Inhibitor Combinations against Candida albicans - Synthesis and Biological Activity of New 2,4-Diaminopyrimidines and 4′-Substituted 4-Aminodiphenyl Sulfones
Otzen, Thomas,Wempe, Ellen G.,Kunz, Brigitte,Bartels, Rainer,Lehwark-Yvetot, Gudrun,H?nsel, Wolfram,Schaper, Klaus-Jürgen,Seydel, Joachim K.
, p. 240 - 253 (2007/10/03)
The paper describes the design, synthesis, and testing of inhibitors of folate-synthesizing enzymes and of whole cell cultures of Candida albicans. The target enzymes used were dihydropteroic acid synthase (SYN) and dihydrofolate reductase (DHFR). Several series of new 2,4-diaminopyrimidines were synthesized and tested as inhibitors of DHFR and compared with their activity against DHFR derived from mycobacteria and Escherichia coli. To test for selectivity, also rat DHFR was used. A series of substituted 4-aminodiphenyl sulfones was tested for inhibitory activity against SYN and the I50 values compared to those obtained previously against Plasmodium berghei- and E. coll-derived SYN. Surprisingly, QSAR equations show very similar structural dependencies. To find an explanation for the large difference in the I50 values observed for enzyme inhibition (SYN, DHFR) and for inhibition of cell cultures of Candida, mutant strains with overexpressed efflux pumps and strains in which such pumps are deleted were included in the study and the MICs compared. Efflux pumps were responsible for the low activity of some of the tested derivatives, others showed no increase in activity after pumps were knocked out. In this case it may be speculated that these derivatives are not able to enter the cells.
Synthesis of Some Substituted Guanidinopyrimidines and their Structural Assignment by 13C and 1H NMR
Ladd, David L.
, p. 917 - 921 (2007/10/02)
A series of substituted 2- and 4-guanidinopyrimidines were prepared by reaction of halopyrimidines with guanidine; alkylamino and amino substituents were introduced by subsequent halogen replacement by primary amines or ammonia or the catalytic reduction of nitro groups.Structural assignments were made on the basis of 13C and 1H nmr.A guanidinopteridine and a bispyrimidinylguanidine were also synthesized.Some unsuccessful reaction illustrated the low nucleophilic reactivity and thermal instability of the guanidine group.
