1622-57-7Relevant articles and documents
2-aminobenzimidazoles for leishmaniasis: From initial hit discovery to in vivo profiling
Ferreira, Rafael Augusto Alves,Junior, Celso de Oliveira Rezende,Martinez, Pablo David Grigol,Koovits, Paul John,Soares, Bruna Miranda,Ferreira, Leonardo L. G.,Michelan-Duarte, Simone,Chelucci, Rafael Consolin,Andricopulo, Adriano D.,Galuppo, Mariana K.,Uliana, Silvia R. B.,Matheeussen, An,Caljon, Guy,Maes, Louis,Campbell, Simon,Kratz, Jadel M.,Mowbray, Charles E.,Dias, Luiz Carlos
, (2021/03/24)
Leishmaniasis is a major infectious disease with hundreds of thousands of new cases and over 20,000 deaths each year. The current drugs to treat this life-threatening infection have several drawbacks such as toxicity and long treatment regimens. A library of 1.8 million compounds, from which the hits reported here are publicly available, was screened against Leishmania infantum as part of an optimization program; a compound was found with a 2-aminobenzimidazole functionality presenting moderate potency, low metabolic stability and high lipophilicity. Several rounds of synthesis were performed to incorporate chemical groups capable of reducing lipophilicity and clearance, leading to the identification of compounds that are active against different parasite strains and have improved in vitro proper-ties. As a result of this optimization program, a group of compounds was further tested in anticipation of in vivo evaluation. In vivo tests were carried out with compounds 29 (L. infantum IC50: 4.1 μM) and 39 (L. infantum IC50: 0.5 μM) in an acute L. infantum VL mouse model, which showed problems of poor exposure and lack of efficacy, despite the good in vitro potency.
Hit-to-lead optimization of novel benzimidazole phenylacetamides as broad spectrum trypanosomacides
Avery, Vicky M.,Baell, Jonathan,McNamara, Nicole,Rahmani, Raphael,Sykes, Melissa L.
supporting information, p. 685 - 695 (2020/08/24)
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
Benzimidazole compound and application thereof
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Paragraph 0194; 0198; 0199, (2019/01/07)
The invention relates to a benzimidazole compound and an application thereof. The structure of the benzimidazole compound is shown as a formula I, and the compound is used as a focal adhesion kinase inhibitor and shows relatively good focal adhesion kinase (FAK) inhibition activity. Meanwhile, the benzimidazole compound has stronger medicine effect and better pharmacokinetic property and/or toxicological characteristics, such as good brain/plasma ratio, good bioavailability, good metabolic stability, and reduced inhibition to respiratory action of mitochondria. The benzimidazole compound has agood clinical application prospect.
