620597-98-0Relevant articles and documents
Nitrotriazole-based acetamides and propanamides with broad spectrum antitrypanosomal activity
Papadopoulou, Maria V.,Bloomer, William D.,Rosenzweig, Howard S.,Wilkinson, Shane R.,Szular, Joanna,Kaiser, Marcel
, p. 895 - 904 (2016)
3-Nitro-1H-1,2,4-triazole-based acetamides bearing a biphenyl- or a phenoxyphenyl moiety have shown remarkable antichagasic activity both in?vitro and in an acute murine model, as well as substantial in?vitro antileishmanial activity but lacked activity against human African trypanosomiasis. We have shown now that by inserting a methylene group in the linkage to obtain the corresponding propanamides, both antichagasic and in particular anti-human African trypanosomiasis potency was increased. Therefore, IC50values at low nM concentrations against both T.?cruzi and T.?b. rhodesiense, along with huge selectivity indices were obtained. Although several propanamides were active against Leishmania donovani, they were slightly less potent than their corresponding acetamides. There was a good correlation between lipophilicity (clogP value) and trypanocidal activity, for all new compounds. Type I nitroreductase, an enzyme absent from the human host, played a role in the activation of the new compounds, which may function as prodrugs. Antichagasic activity in?vivo was also demonstrated with representative propanamides.
Application of a novel design paradigm to generate general nonpeptide combinatorial scaffolds mimicking beta turns: Synthesis of ligands for somatostatin receptors
Chianelli, Dona,Kim, Yong-Chul,Lvovskiy, Dmitriy,Webb, Thomas R.
, p. 5059 - 5068 (2007/10/03)
Nonpeptide compounds that mimic bioactive peptides are desirable for a number of clinical indications. We report a new practical method for the design of scaffolds exhibiting drug-like properties that are suitable for the display of peptide pharmacophores
