Molecules (Oct 2021)
T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4<i>H</i>-pyrido[3,2-<i>e</i>][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite <i>Trypanosoma brucei</i>
- 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
Affiliations
- Lee J. Silverberg
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Tapas K. Mal
- Department of Chemistry, Pennsylvania State University, 104 Chemistry Building, Room 08, University Park, State College, PA 16802, USA
- Carlos N. Pacheco
- Department of Chemistry, Pennsylvania State University, 104 Chemistry Building, Room 08, University Park, State College, PA 16802, USA
- Megan L. Povelones
- Mendel Science Center, Department of Biology, Villanova University, 800 Lancaster Avenue, Villanova, PA 19085, USA
- Madeline F. Malfara
- Mendel Science Center, Department of Biology, Villanova University, 800 Lancaster Avenue, Villanova, PA 19085, USA
- Anthony F. Lagalante
- Mendel Science Center, Department of Chemistry, Villanova University, 800 Lancaster Avenue, Villanova, PA 19085, USA
- Mark A. Olsen
- Mendel Science Center, Department of Chemistry, Villanova University, 800 Lancaster Avenue, Villanova, PA 19085, USA
- Hemant P. Yennawar
- Department of Biochemistry and Molecular Biology, Pennsylvania State University, 8 Althouse Laboratory, University Park, State College, PA 16802, USA
- Hany F. Sobhi
- Center for Organic Synthesis Coppin State University, Room-229, 2500 West North Avenue, Baltimore, MD 21216, USA
- Kayla R. Baney
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Robin L. Bozeman
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Craig S. Eroh
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Michael J. Fleming
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Tracy L. Garcia
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Casey L. Gregory
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Julia E. Hahn
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Alyssa M. Hatter
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Lexi L. Johns
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Tianna L. Klinger
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Jennie J. Li
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Andrew J. Menig
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Grace C. Muench
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Melissa E. Ramirez
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Jordyn Reilly
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Nicole Sacco
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Alexandra M. Sheidy
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Marla M. Stoner
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Eric N. Thompson
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- Soroush F. Yazdani
- Schuylkill Campus, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA
- DOI
- https://doi.org/10.3390/molecules26206099
- Journal volume & issue
-
Vol. 26,
no. 20
p. 6099
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 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.
Keywords
