2347-38-8Relevant academic research and scientific papers
Antikinetoplastid antimitotic activity and metabolic stability of dinitroaniline sulfonamides and benzamides
George, Tesmol G.,Johnsamuel, Jayaseharan,Delfin, Dawn A.,Yakovich, Adam,Mukherjee, Mitali,Phelps, Mitch A.,Dalton, James T.,Sackett, Dan L.,Kaiser, Marcel,Brun, Reto,Werbovetz, Karl A.
, p. 5699 - 5710 (2007/10/03)
N1-Phenyl-3,5-dinitro-N4,N4-di-n-propylsulfanilamide (1) and N1-phenyl-3,5-dinitro-N4,N4-di-n-butylsulfanilamide (2) show potent in vitro antimitotic activity against kinetoplastid parasites but display poor in vivo activity. Seventeen new dinitroaniline sulfonamide and eleven new benzamide analogs of these leads are reported here. Nine of the sulfonamides display in vitro IC50 values under 500 nM against African trypanosomes, and the most active antikinetoplastid compounds also inhibit the in vitro assembly of purified leishmanial tubulin with potencies similar to that of 2. While several of the potent compounds are rapidly degraded by rat liver S9 fractions in vitro, N1-(3-hydroxy)phenyl-3,5-dinitro-N4,N4-di-n-butylsulfanilamide (21) displays an IC50 value of 260 nM against African trypanosomes in vitro and is more stable than 2 in the in vitro metabolism assay.
Synthesis and evaluation of dinitroanilines for treatment of cryptosporidiosis
Benbow, John W.,Bernberg, Erin L.,Korda, Anna,Mead, Jan R.
, p. 339 - 343 (2007/10/03)
The efficacy of a series of dinitroaniline herbicide derivatives for the treatment of Cryptosporidium parvum infections has been studied. The lead compounds oryzalin (compound 1) and trifluralin (compound 2) have low water solubility (3 ppm) which was alleged to be a major contributor to their poor pharmacokinetic availability. Derivatives of compounds 1 and 2 were synthesized. In these derivatives the functionality at the C-1 amine position or the C-4 position was substituted with groups with various hydrophilicities to determine if a direct relation existed between water solubility and overall activity. The chlorinated precursors of these derivatives were also examined and were found to be less active in the C. parvum assays, a result in direct contrast to earlier work with Leishmania. Enhanced water solubility alone did not overcome the drug availability problem; however, several candidates with similar activities but with toxicities lower than those of the lead compounds were produced.
