- Hit-to-lead optimization of novel benzimidazole phenylacetamides as broad spectrum trypanosomacides
-
Trypanosoma cruzi and Trypanosoma brucei are the parasitic causative agents of Chagas disease and human African trypanosomiasis (HAT), respectively. The drugs currently used to treat these diseases are not efficacious against all stages and/or parasite sub-species, often displaying side effects. Herein, we report the SAR exploration of a novel hit, 2-(4-chlorophenyl)-N-(1-propyl-1H-benzimidazol-2-yl)acetamide previously identified from high throughput screens against T. cruzi, Trypanosoma brucei brucei and Leishmania donovani. An informative set of analogues was synthesized incorporating key modifications of the scaffold resulting in improved potency whilst the majority of compounds retained low cytotoxicity against H9c2 and HEK293 cell lines. The SAR observed against T. cruzi broadly matches that observed against T.b. brucei, suggesting the possibility for a broad-spectrum candidate. This class of compounds therefore warrants further investigation towards development as a treatment for Chagas disease and HAT. This journal is
- Avery, Vicky M.,Baell, Jonathan,McNamara, Nicole,Rahmani, Raphael,Sykes, Melissa L.
-
supporting information
p. 685 - 695
(2020/08/24)
-
- HOMOGENEOUS TIME RESOLVED FLUORESCENCE BASED TEST SYSTEM
-
The present invention concerns a fluorescence resonance energy transfer based high throughput test system to measure the formation of the HIV gp41 six-helix bundle. In a first embodiment the current invention relates to a homogeneous time resolved fluorescence-based test system comprising a first helical polypeptide consisting essentially of the sequence of IQN36 (SEQ ID NO:1); a second helical polypeptide consisting essentially of the sequence of C34 (SEQ ID NO: 2) wherein said IQN36 is labeled with a light emitting fluorophore and said C34 is labeled with an ultra-violet excitable fluorophore.
- -
-
Page/Page column 54-55
(2010/12/29)
-
- Organic compounds
-
The present invention relates to novel benzimidazole derivatives, their preparation, their use as pharmaceuticals and pharmaceutical compositions containing them, wherein the compounds have the formula (I): in which the substitutents are as defined in claim 1 and salts, solvates, hydrates and N-oxides thereof.
- -
-
Page/Page column 19
(2009/05/29)
-
- NICOTINIC ACID DERIVATIVES AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR-5
-
The present invention relates to novel benzimidazole derivatives, their preparation, their use as pharmaceuticals and pharmaceutical compositions containing them, wherein the compounds have the Formula (I): in which the substitutents are as defined in claim 1 and and salts, solvates, hydrates and N- oxides thereof.
- -
-
Page/Page column 45
(2008/12/08)
-