Dideaza compounds with N substitution

In another recent study, Caperelli and Conigliaro [170] synthesized 10-formyl-5,8-dideazafolic acid (IV.307) and 10-acetyl-5,8-dideazafolic acid (IV.308). Compound (IV.307) was obtained from 5,8-dideazafolic acid in 80% 

Nair et al. [171] confirmed in 1983 that CB3717 was a much more potent inhibitor of TS than of DHFR in assays using bacterial enzymes. Against TS and DHFR from L. casei, the IC50 values were 0.013 and 22 /xM, respectively, while against the same enzymes from S.faecium the corresponding ICso values were 0.01 and 0.3 /xM. Thus, the different effect between TS and DHFR inhibition appeared to be species-related, with the S. faecium enzyme probably being more predictive of the effect on mammalian enzyme. In the same 

The effect of -substitution on TS-inhibitory potency in vitro has been examined in detail [169]. Of the 13 representative compounds tested, only two, the V -ethyl (IV.293) and 2V -(2-fluoroethyl) (IV.296) analogues had IC50 values that were 5-fold greater than the IC50 of CB3717. The IC50 

Diddens et al. [ 180] examined the activity of CB3717 against several human 

In an exciting development that promises to be of theoretical as well as clinical interest, Jones et al. [185] recently disclosed the synthesis of a new series of CB3717 analogues (IV.316)-(IV.320) lacking a 2-amino group. These 

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