Dataset Information

2,4-Diamino-6-methylpyrimidines for the potential treatment of Chagas' disease.

ABSTRACT: Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, affects 8-10 million people across the Latin American population and is responsible for around 12,500 deaths per annum. The current frontline treatments, benznidazole and nifurtimox, are associated with side effects and lack efficacy in the chronic stage of the disease, leading to an urgent need for new treatments. A high throughput screening campaign against the physiologically relevant intracellular form of the parasite identified a series of 2,4-diamino-6-methylpyrimidines. Demonstrating the series did not work through the anti-target TcCYP51, and was generally cytocidal, confirmed its suitability for further development. This study reports the optimisation of selectivity and metabolic stability of the series and identification of a suitable lead for further optimisation.

SUBMITTER: Thomas MG

PROVIDER: S-EPMC6970618 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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2,4-Diamino-6-methylpyrimidines for the potential treatment of Chagas' disease.

Thomas Michael G MG De Rycker Manu M Cotillo Torrejon Ignacio I Thomas John J Riley Jennifer J Spinks Daniel D Read Kevin D KD Miles Tim J TJ Gilbert Ian H IH Wyatt Paul G PG

Bioorganic & medicinal chemistry letters 20180803 18

Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, affects 8-10 million people across the Latin American population and is responsible for around 12,500 deaths per annum. The current frontline treatments, benznidazole and nifurtimox, are associated with side effects and lack efficacy in the chronic stage of the disease, leading to an urgent need for new treatments. A high throughput screening campaign against the physiologically relevant intracellular form of the parasite ident ...[more]

PMID: 30104093

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Project description:According to World Health Organization (WHO) prevalence estimates, 1.1 million people in Mexico are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease (CD). However, limited information is available about access to antitrypanosomal treatment. This study assesses the extent of access in Mexico, analyzes the barriers to access, and suggests strategies to overcome them.Semi-structured in-depth interviews were conducted with 18 key informants and policymakers at the national level in Mexico. Data on CD cases, relevant policy documents and interview data were analyzed using the Flagship Framework for Pharmaceutical Policy Reform policy interventions: regulation, financing, payment, organization, and persuasion. Data showed that 3,013 cases were registered nationally from 2007-2011, representing 0.41% of total expected cases based on Mexico's national prevalence estimate. In four of five years, new registered cases were below national targets by 11-36%. Of 1,329 cases registered nationally in 2010-2011, 834 received treatment, 120 were pending treatment as of January 2012, and the treatment status of 375 was unknown. The analysis revealed that the national program mainly coordinated donation of nifurtimox and that important obstacles to access include the exclusion of antitrypanosomal medicines from the national formulary (regulation), historical exclusion of CD from the social insurance package (organization), absence of national clinical guidelines (organization), and limited provider awareness (persuasion).Efforts to treat CD in Mexico indicate an increased commitment to addressing this disease. Access to treatment could be advanced by improving the importation process for antitrypanosomal medicines and adding them to the national formulary, increasing education for healthcare providers, and strengthening clinical guidelines. These recommendations have important implications for other countries in the region with similar problems in access to treatment for CD.

Dataset Information

2,4-Diamino-6-methylpyrimidines for the potential treatment of Chagas' disease.

Publications

2,4-Diamino-6-methylpyrimidines for the potential treatment of Chagas' disease.

Similar Datasets

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