Antifolate azides

The glutamic moiety of TNP-351, a pyrrolo[2,3-d]pyrimidine glutamic acid derivative, and related compounds have been transformed into their A-co-masked ornithine analogs which show remarkable antifolate activity <00CPB1270>. The reaction of the heterocyclic enamine 77 with tosyl azide leads to the tosylimino derivative of 1,2,4-triazolo[l, 5-a]pyrimidine 79. Extrusion of nitrogen from the primary adduct 78 is followed by a 1,2-shift of a methyl group to yield 79 <00JHC195>. 

MEDICINAL AZIDES Antiproliferative azides Azido-substituted antifolates Azidotriazenes Myo-mositol analogues Azidonucleoside antitumour agents Azido-substituted anti-infective agents Zidovudine and related nucleosides A zido-substituted antibiotics Miscellaneous anti-infective azide derivatives Anti-inflammatory azides Zidometacin... 

Figure 3.7. Modulation of antifolate activity as a consequence of azide bioreduction.

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