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

Lee J. Silverberg; Tapas K. Mal; Carlos N. Pacheco; Megan L. Povelones; Madeline F. Malfara; Anthony F. Lagalante; Mark A. Olsen; Hemant P. Yennawar; Hany F. Sobhi; Kayla R. Baney; Robin L. Bozeman; Craig S. Eroh; Michael J. Fleming; Tracy L. Garcia; Casey L. Gregory; Julia E. Hahn; Alyssa M. Hatter; Lexi L. Johns; Tianna L. Klinger; Jennie J. Li; Andrew J. Menig; Grace C. Muench; Melissa E. Ramirez; Jordyn Reilly; Nicole Sacco; Alexandra M. Sheidy; Marla M. Stoner; Eric N. Thompson; Soroush F. Yazdani

doi:10.3390/molecules26206099

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

Lee J. Silverberg, Tapas K. Mal, Carlos N. Pacheco, Megan L. Povelones, Madeline F. Malfara, Anthony F. Lagalante, Mark A. Olsen, Hemant P. Yennawar, Hany F. Sobhi, Kayla R. Baney, Robin L. Bozeman, Craig S. Eroh, Michael J. Fleming, Tracy L. Garcia, Casey L. Gregory, Julia E. Hahn, Alyssa M. Hatter, Lexi L. Johns, Tianna L. Klinger, Jennie J. LiAndrew J. Menig, Grace C. Muench, Melissa E. Ramirez, Jordyn Reilly, Nicole Sacco, Alexandra M. Sheidy, Marla M. Stoner, Eric N. Thompson, Soroush F. Yazdani

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Abstract

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 thion-icotinic 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.

Original language	English (US)
Article number	6099
Journal	Molecules
Volume	26
Issue number	20
DOIs	https://doi.org/10.3390/molecules26206099
State	Published - Oct 1 2021

All Science Journal Classification (ASJC) codes

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

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Silverberg, L. J., Mal, T. K., Pacheco, C. N., Povelones, M. L., Malfara, M. F., Lagalante, A. F., Olsen, M. A., Yennawar, H. P., Sobhi, H. F., Baney, K. R., Bozeman, R. L., Eroh, C. S., Fleming, M. J., Garcia, T. L., Gregory, C. L., Hahn, J. E., Hatter, A. M., Johns, L. L., Klinger, T. L., ... Yazdani, S. F. (2021). 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. Molecules, 26(20), Article 6099. https://doi.org/10.3390/molecules26206099

@article{6fbc7d0e333a4983b37a9eb3ba7ad47c,

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",

abstract = "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 thion-icotinic 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.",

author = "Silverberg, {Lee J.} and Mal, {Tapas K.} and Pacheco, {Carlos N.} and Povelones, {Megan L.} and Malfara, {Madeline F.} and Lagalante, {Anthony F.} and Olsen, {Mark A.} and Yennawar, {Hemant P.} and Sobhi, {Hany F.} and Baney, {Kayla R.} and Bozeman, {Robin L.} and Eroh, {Craig S.} and Fleming, {Michael J.} and Garcia, {Tracy L.} and Gregory, {Casey L.} and Hahn, {Julia E.} and Hatter, {Alyssa M.} and Johns, {Lexi L.} and Klinger, {Tianna L.} and Li, {Jennie J.} and Menig, {Andrew J.} and Muench, {Grace C.} and Ramirez, {Melissa E.} and Jordyn Reilly and Nicole Sacco and Sheidy, {Alexandra M.} and Stoner, {Marla M.} and Thompson, {Eric N.} and Yazdani, {Soroush F.}",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = oct,

day = "1",

doi = "10.3390/molecules26206099",

language = "English (US)",

volume = "26",

journal = "Molecules",

issn = "1420-3049",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "20",

}

Silverberg, LJ , Mal, TK, Pacheco, CN, Povelones, ML, Malfara, MF, Lagalante, AF, Olsen, MA, Yennawar, HP, Sobhi, HF, Baney, KR, Bozeman, RL, Eroh, CS, Fleming, MJ, Garcia, TL, Gregory, CL, Hahn, JE, Hatter, AM, Johns, LL, Klinger, TL, Li, JJ, Menig, AJ, Muench, GC, Ramirez, ME, Reilly, J, Sacco, N, Sheidy, AM, Stoner, MM, Thompson, EN & Yazdani, SF 2021, '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', Molecules, vol. 26, no. 20, 6099. https://doi.org/10.3390/molecules26206099

TY - JOUR

T1 - 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

AU - Silverberg, Lee J.

AU - Mal, Tapas K.

AU - Pacheco, Carlos N.

AU - Povelones, Megan L.

AU - Malfara, Madeline F.

AU - Lagalante, Anthony F.

AU - Olsen, Mark A.

AU - Yennawar, Hemant P.

AU - Sobhi, Hany F.

AU - Baney, Kayla R.

AU - Bozeman, Robin L.

AU - Eroh, Craig S.

AU - Fleming, Michael J.

AU - Garcia, Tracy L.

AU - Gregory, Casey L.

AU - Hahn, Julia E.

AU - Hatter, Alyssa M.

AU - Johns, Lexi L.

AU - Klinger, Tianna L.

AU - Li, Jennie J.

AU - Menig, Andrew J.

AU - Muench, Grace C.

AU - Ramirez, Melissa E.

AU - Reilly, Jordyn

AU - Sacco, Nicole

AU - Sheidy, Alexandra M.

AU - Stoner, Marla M.

AU - Thompson, Eric N.

AU - Yazdani, Soroush F.

PY - 2021/10/1

Y1 - 2021/10/1

N2 - 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 thion-icotinic 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.

AB - 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 thion-icotinic 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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UR - http://www.scopus.com/inward/citedby.url?scp=85117223866&partnerID=8YFLogxK

U2 - 10.3390/molecules26206099

DO - 10.3390/molecules26206099

M3 - Article

C2 - 34684680

AN - SCOPUS:85117223866

SN - 1420-3049

VL - 26

JO - Molecules

JF - Molecules

IS - 20

M1 - 6099

ER -

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

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