178948-91-9Relevant academic research and scientific papers
Design and synthesis of Mannich base-type derivatives containing imidazole and benzimidazole as lead compounds for drug discovery in Chagas Disease
Beltran-Hortelano, Iván,Atherton, Richard L.,Rubio-Hernández, Mercedes,Sanz-Serrano, Julen,Alcolea, Verónica,Kelly, John M.,Pérez-Silanes, Silvia,Olmo, Francisco
, (2021/07/14)
The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, the most important parasitic infection in Latin America. The only treatments currently available are nitro-derivative drugs that are characterised by high toxicity and limited efficacy. Therefore, there is an urgent need for more effective, less toxic therapeutic agents. We have previously identified the potential for Mannich base derivatives as novel inhibitors of this parasite. To further explore this family of compounds, we synthesised a panel of 69 new analogues, based on multi-parametric structure-activity relationships, which allowed optimization of both anti-parasitic activity, physicochemical parameters and ADME properties. Additionally, we optimized our in vitro screening approaches against all three developmental forms of the parasite, allowing us to discard the least effective and trypanostatic derivatives at an early stage. We ultimately identified derivative 3c, which demonstrated excellent trypanocidal properties, and a synergistic mode of action against trypomastigotes in combination with the reference drug benznidazole. Both its druggability and low-cost production make this derivative a promising candidate for the preclinical, in vivo assays of the Chagas disease drug-discovery pipeline.
Organic compounds
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Page/Page column 78, (2010/11/26)
The present invention provides a compound of formula I: Said compound is inhibitor of aldosterone synthase and aromatase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase or aromatase. Accordingly, the compound of formula I can be used in treatment of hypokalemia, hypertension, congestive heart failure, atrial fibrillation, renal failure, in particular, chronic renal failure, restenosis, atherosclerosis, syndrome X, obesity, nephropathy, post-myocardial infarction, coronary heart diseases, inflammation, increased formation of collagen, fibrosis such as cardiac or myocardiac fibrosis and remodeling following hypertension and endothelial dysfunction, gynecomastia, osteoporosis, prostate cancer, endometriosis, uterine fibroids, dysfunctional uterine bleeding, endometrial hyperplasia, polycystic ovarian disease, infertility, fibrocystic breast disease, breast cancer and fibrocystic mastopathy. Finally, the present invention also provides a pharmaceutical composition.
