Cargando…
Structure–Property Optimization of a Series of Imidazopyridines for Visceral Leishmaniasis
[Image: see text] Leishmaniasis is a collection of diseases caused by more than 20 Leishmania parasite species that manifest as either visceral, cutaneous, or mucocutaneous leishmaniasis. Despite the significant mortality and morbidity associated with leishmaniasis, it remains a neglected tropical d...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
|
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10425983/ https://www.ncbi.nlm.nih.gov/pubmed/37417544 http://dx.doi.org/10.1021/acsinfecdis.3c00040 |
_version_ | 1785089957591777280 |
---|---|
author | Dichiara, Maria Simpson, Quillon J. Quotadamo, Antonio Jalani, Hitesh B. Huang, Anson X. Millard, Caroline C. Klug, Dana M. Tse, Edwin G. Todd, Matthew H. Silva, Daniel Gedder da Silva Emery, Flavio Carlson, J. Eric Zheng, Shao-Liang Vleminckx, Margot Matheeussen, An Caljon, Guy Pollastri, Michael P. Sjö, Peter Perry, Benjamin Ferrins, Lori |
author_facet | Dichiara, Maria Simpson, Quillon J. Quotadamo, Antonio Jalani, Hitesh B. Huang, Anson X. Millard, Caroline C. Klug, Dana M. Tse, Edwin G. Todd, Matthew H. Silva, Daniel Gedder da Silva Emery, Flavio Carlson, J. Eric Zheng, Shao-Liang Vleminckx, Margot Matheeussen, An Caljon, Guy Pollastri, Michael P. Sjö, Peter Perry, Benjamin Ferrins, Lori |
author_sort | Dichiara, Maria |
collection | PubMed |
description | [Image: see text] Leishmaniasis is a collection of diseases caused by more than 20 Leishmania parasite species that manifest as either visceral, cutaneous, or mucocutaneous leishmaniasis. Despite the significant mortality and morbidity associated with leishmaniasis, it remains a neglected tropical disease. Existing treatments have variable efficacy, significant toxicity, rising resistance, and limited oral bioavailability, which necessitates the development of novel and affordable therapeutics. Here, we report on the continued optimization of a series of imidazopyridines for visceral leishmaniasis and a scaffold hop to a series of substituted 2-(pyridin-2-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazoles with improved absorption, distribution, metabolism, and elimination properties. |
format | Online Article Text |
id | pubmed-10425983 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-104259832023-08-16 Structure–Property Optimization of a Series of Imidazopyridines for Visceral Leishmaniasis Dichiara, Maria Simpson, Quillon J. Quotadamo, Antonio Jalani, Hitesh B. Huang, Anson X. Millard, Caroline C. Klug, Dana M. Tse, Edwin G. Todd, Matthew H. Silva, Daniel Gedder da Silva Emery, Flavio Carlson, J. Eric Zheng, Shao-Liang Vleminckx, Margot Matheeussen, An Caljon, Guy Pollastri, Michael P. Sjö, Peter Perry, Benjamin Ferrins, Lori ACS Infect Dis [Image: see text] Leishmaniasis is a collection of diseases caused by more than 20 Leishmania parasite species that manifest as either visceral, cutaneous, or mucocutaneous leishmaniasis. Despite the significant mortality and morbidity associated with leishmaniasis, it remains a neglected tropical disease. Existing treatments have variable efficacy, significant toxicity, rising resistance, and limited oral bioavailability, which necessitates the development of novel and affordable therapeutics. Here, we report on the continued optimization of a series of imidazopyridines for visceral leishmaniasis and a scaffold hop to a series of substituted 2-(pyridin-2-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazoles with improved absorption, distribution, metabolism, and elimination properties. American Chemical Society 2023-07-07 /pmc/articles/PMC10425983/ /pubmed/37417544 http://dx.doi.org/10.1021/acsinfecdis.3c00040 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Dichiara, Maria Simpson, Quillon J. Quotadamo, Antonio Jalani, Hitesh B. Huang, Anson X. Millard, Caroline C. Klug, Dana M. Tse, Edwin G. Todd, Matthew H. Silva, Daniel Gedder da Silva Emery, Flavio Carlson, J. Eric Zheng, Shao-Liang Vleminckx, Margot Matheeussen, An Caljon, Guy Pollastri, Michael P. Sjö, Peter Perry, Benjamin Ferrins, Lori Structure–Property Optimization of a Series of Imidazopyridines for Visceral Leishmaniasis |
title | Structure–Property
Optimization of a Series
of Imidazopyridines for Visceral Leishmaniasis |
title_full | Structure–Property
Optimization of a Series
of Imidazopyridines for Visceral Leishmaniasis |
title_fullStr | Structure–Property
Optimization of a Series
of Imidazopyridines for Visceral Leishmaniasis |
title_full_unstemmed | Structure–Property
Optimization of a Series
of Imidazopyridines for Visceral Leishmaniasis |
title_short | Structure–Property
Optimization of a Series
of Imidazopyridines for Visceral Leishmaniasis |
title_sort | structure–property
optimization of a series
of imidazopyridines for visceral leishmaniasis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10425983/ https://www.ncbi.nlm.nih.gov/pubmed/37417544 http://dx.doi.org/10.1021/acsinfecdis.3c00040 |
work_keys_str_mv | AT dichiaramaria structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT simpsonquillonj structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT quotadamoantonio structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT jalanihiteshb structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT huangansonx structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT millardcarolinec structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT klugdanam structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT tseedwing structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT toddmatthewh structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT silvadanielgedder structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT dasilvaemeryflavio structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT carlsonjeric structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT zhengshaoliang structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT vleminckxmargot structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT matheeussenan structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT caljonguy structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT pollastrimichaelp structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT sjopeter structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT perrybenjamin structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis AT ferrinslori structurepropertyoptimizationofaseriesofimidazopyridinesforvisceralleishmaniasis |