113494-40-9Relevant articles and documents
Antifolate agents
-
, (2008/06/13)
2,4-Diamino-5-phenylpyrimidines in the form of the free base or an acid addition salt thereof are provided having the structural formula (I): STR1 wherein R1 is an alkoxy, aralkoxy or a mono-substituted or disubstituted amino group, R2 is a nitro group, and R3 is an alkyl group. The compounds act as antifolate agents and are useful for therapeutic treatment, for example as antitumour agents, antipsoriatic agents, antibacterial agents, antitrypanosomal agents and antimalarial agents. Pharmaceutical preparations comprising these compounds for administration to mammals, and methods for preparing the compounds, are disclosed. Particularly useful new compounds, especially for antitumour therapy, have the structural formula IA: STR2 in which formula IA: n is 1-6; R1 represents hydrogen or alkyl; R4, R5 and R6, which may be identical or different, each represnt hydrogen, alkyl, alkoxy, halo, nitro, perfluoroalkyl, a group of formula --CO2 Ra wherein Ra represents hydrogen, alkyl or alkoxyalkyl, or a group of formula --COBRb Rc wherein Rb and Rc which may be identical or different each represent alkyl; and R3 represents alkyl.
Stuctural Studies on Bio-active Compounds. Part 5. Synthesis and Properties of 2,4-Diaminopyrimidine Dihydrofolate Reductase Inhibitors bearing Lipophilic Azido Groups
Bliss, Edward A.,Griffin, Roger J.,Stevens, Malcolm F. G.
, p. 2217 - 2228 (2007/10/02)
A series of 2,4-diamino-5-(azidoaryl)-6-alkylpyrimidines has been prepared.The azide (36) (MZP) can be reduced by thiol reagents to the corresponding amine (28) but reductive deazidation occured when the series of azidophenyl derivatives was heated with hydrazine hydrate.Degradation of azide (36) in a trifluoroacetic acid-trifluoromethanesulphonic acid mixture at 0 deg C affords a means of introducing the bulky trifluoromethylsulphonyloxy substituent into the hindered ortho-position of the 5-aryl substituent.The products formed from thermolysis and photolysis of the azide (36) and the planar analogue 2,4-diamino-6-azidoquinazoline (70) derive from the triplet nitrene reactive intermediates. The azido compounds are potent inhibitors of rat liver dihydrofolate reductase although not as active as metoprin.The azide (36), as its ethanesulphonic acid salt, was selected for clinical trial on the basis of its ease of synthesis and suitable biological and pharmaceutical properties, and has a shorter biological half-life than compounds of comparable hydrophobicity.