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T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei

A series of fourteen 2-aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones was prepared at room temperature by T3P-mediated cyclization of N-phenyl-C-aryl imines with thionicotinic acid, two difficult substrates. The reactions were operationally simple, did not require specialized equipmen...

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Autores principales: Silverberg, Lee J., Mal, Tapas K., Pacheco, Carlos N., Povelones, Megan L., Malfara, Madeline F., Lagalante, Anthony F., Olsen, Mark A., Yennawar, Hemant P., Sobhi, Hany F., Baney, Kayla R., Bozeman, Robin L., Eroh, Craig S., Fleming, Michael J., Garcia, Tracy L., Gregory, Casey L., Hahn, Julia E., Hatter, Alyssa M., Johns, Lexi L., Klinger, Tianna L., Li, Jennie J., Menig, Andrew J., Muench, Grace C., Ramirez, Melissa E., Reilly, Jordyn, Sacco, Nicole, Sheidy, Alexandra M., Stoner, Marla M., Thompson, Eric N., Yazdani, Soroush F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540051/
https://www.ncbi.nlm.nih.gov/pubmed/34684680
http://dx.doi.org/10.3390/molecules26206099
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author Silverberg, Lee J.
Mal, Tapas K.
Pacheco, Carlos N.
Povelones, Megan L.
Malfara, Madeline F.
Lagalante, Anthony F.
Olsen, Mark A.
Yennawar, Hemant P.
Sobhi, Hany F.
Baney, Kayla R.
Bozeman, Robin L.
Eroh, Craig S.
Fleming, Michael J.
Garcia, Tracy L.
Gregory, Casey L.
Hahn, Julia E.
Hatter, Alyssa M.
Johns, Lexi L.
Klinger, Tianna L.
Li, Jennie J.
Menig, Andrew J.
Muench, Grace C.
Ramirez, Melissa E.
Reilly, Jordyn
Sacco, Nicole
Sheidy, Alexandra M.
Stoner, Marla M.
Thompson, Eric N.
Yazdani, Soroush F.
author_facet Silverberg, Lee J.
Mal, Tapas K.
Pacheco, Carlos N.
Povelones, Megan L.
Malfara, Madeline F.
Lagalante, Anthony F.
Olsen, Mark A.
Yennawar, Hemant P.
Sobhi, Hany F.
Baney, Kayla R.
Bozeman, Robin L.
Eroh, Craig S.
Fleming, Michael J.
Garcia, Tracy L.
Gregory, Casey L.
Hahn, Julia E.
Hatter, Alyssa M.
Johns, Lexi L.
Klinger, Tianna L.
Li, Jennie J.
Menig, Andrew J.
Muench, Grace C.
Ramirez, Melissa E.
Reilly, Jordyn
Sacco, Nicole
Sheidy, Alexandra M.
Stoner, Marla M.
Thompson, Eric N.
Yazdani, Soroush F.
author_sort Silverberg, Lee J.
collection PubMed
description A series of fourteen 2-aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones was prepared at room temperature by T3P-mediated cyclization of N-phenyl-C-aryl imines with thionicotinic acid, two difficult substrates. The reactions were operationally simple, did not require specialized equipment or anhydrous solvents, could be performed as either two or three component reactions, and gave moderate–good yields as high as 63%. This provides ready access to N-phenyl compounds in this family, which have been generally difficult to prepare. As part of the study, the first crystal structure of neutral thionicotinic acid is also reported, and showed the molecule to be in the form of the thione tautomer. Additionally, the synthesized compounds were tested against T. brucei, the causative agent of Human African Sleeping Sickness. Screening at 50 µM concentration showed that five of the compounds strongly inhibited growth and killed parasites.
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spelling pubmed-85400512021-10-24 T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei Silverberg, Lee J. Mal, Tapas K. Pacheco, Carlos N. Povelones, Megan L. Malfara, Madeline F. Lagalante, Anthony F. Olsen, Mark A. Yennawar, Hemant P. Sobhi, Hany F. Baney, Kayla R. Bozeman, Robin L. Eroh, Craig S. Fleming, Michael J. Garcia, Tracy L. Gregory, Casey L. Hahn, Julia E. Hatter, Alyssa M. Johns, Lexi L. Klinger, Tianna L. Li, Jennie J. Menig, Andrew J. Muench, Grace C. Ramirez, Melissa E. Reilly, Jordyn Sacco, Nicole Sheidy, Alexandra M. Stoner, Marla M. Thompson, Eric N. Yazdani, Soroush F. Molecules Article A series of fourteen 2-aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones was prepared at room temperature by T3P-mediated cyclization of N-phenyl-C-aryl imines with thionicotinic acid, two difficult substrates. The reactions were operationally simple, did not require specialized equipment or anhydrous solvents, could be performed as either two or three component reactions, and gave moderate–good yields as high as 63%. This provides ready access to N-phenyl compounds in this family, which have been generally difficult to prepare. As part of the study, the first crystal structure of neutral thionicotinic acid is also reported, and showed the molecule to be in the form of the thione tautomer. Additionally, the synthesized compounds were tested against T. brucei, the causative agent of Human African Sleeping Sickness. Screening at 50 µM concentration showed that five of the compounds strongly inhibited growth and killed parasites. MDPI 2021-10-09 /pmc/articles/PMC8540051/ /pubmed/34684680 http://dx.doi.org/10.3390/molecules26206099 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Silverberg, Lee J.
Mal, Tapas K.
Pacheco, Carlos N.
Povelones, Megan L.
Malfara, Madeline F.
Lagalante, Anthony F.
Olsen, Mark A.
Yennawar, Hemant P.
Sobhi, Hany F.
Baney, Kayla R.
Bozeman, Robin L.
Eroh, Craig S.
Fleming, Michael J.
Garcia, Tracy L.
Gregory, Casey L.
Hahn, Julia E.
Hatter, Alyssa M.
Johns, Lexi L.
Klinger, Tianna L.
Li, Jennie J.
Menig, Andrew J.
Muench, Grace C.
Ramirez, Melissa E.
Reilly, Jordyn
Sacco, Nicole
Sheidy, Alexandra M.
Stoner, Marla M.
Thompson, Eric N.
Yazdani, Soroush F.
T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei
title T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei
title_full T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei
title_fullStr T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei
title_full_unstemmed T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei
title_short T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei
title_sort t3p-promoted synthesis of a series of 2-aryl-3-phenyl-2,3-dihydro-4h-pyrido[3,2-e][1,3]thiazin-4-ones and their activity against the kinetoplastid parasite trypanosoma brucei
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540051/
https://www.ncbi.nlm.nih.gov/pubmed/34684680
http://dx.doi.org/10.3390/molecules26206099
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