Research ArticleOpen AccessGoogle Scholar indexed
Synthesis of Substituted Benzothiazepine Compounds with Medicinal Potential
Department of Chemistry, United States Naval Academy, Annapolis, MD, USA
Department of Chemistry, United States Naval Academy, Annapolis, MD, USA
Department of Chemistry, United States Naval Academy, Annapolis, MD, USA
Department of Chemistry, United States Naval Academy, Annapolis, MD, USA
Department of Chemistry, United States Naval Academy, Annapolis, MD, USA
Department of Chemistry, United States Naval Academy, Annapolis, MD, USA
Department of Chemistry, United States Naval Academy, Annapolis, MD, USA
Department of Chemistry, United States Naval Academy, Annapolis, MD, USA
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD, USA
- 1 Department of Chemistry, United States Naval Academy, Annapolis, MD, USA
- 2 Department of Chemistry, United States Naval Academy, Annapolis, MD, USA
- 3 Department of Chemistry, United States Naval Academy, Annapolis, MD, USA
- 4 Department of Chemistry, United States Naval Academy, Annapolis, MD, USA
- 5 Department of Chemistry, United States Naval Academy, Annapolis, MD, USA
- 6 Department of Chemistry, United States Naval Academy, Annapolis, MD, USA
- 7 Department of Chemistry, United States Naval Academy, Annapolis, MD, USA
- 8 Department of Chemistry, United States Naval Academy, Annapolis, MD, USA
- 9 Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD, USA
International Journal of Organic Chemistry·Volume 10 (2020)·Pages 123–134·Published 16 September 2020·DOI10.4236/ijoc.2020.103009
Copy link · social · email
Abstract
A versatile synthetic approach toward a series of benzothiazepines with medicinal potential (for example, compound 1 ) that allows incorporation of structural variation at the three aromatic regions of the structure, and at the sulfur atom, was developed. Knoevenagel condensation of indan-1,3-diones with benzaldehydes, yielded 2-benzylidineindan-1,3-diones, which undewent thio-Michael addition and intramolecular imine formation upon reaction with 2-aminothiophenols, to produce the target benzothiazepines. Use of indan-1,3-diones, benzaldehydes or 2-aminothiophenols bearing further substitution enabled production of novel 5,11-dihydro-12H-benzo[b]indeno [1,2-e][1,4]thiazepin-12-one analogs 1 - 14 , including compounds bearing substitution at novel positions within the scaffold.
KeywordsBenzothiazepineKnoevenagel CondensationThio-Michael AdditionBenzylidene Indandione2-Aminothiophenol
- Krysin, M.Y., Petrov, V.V., Shikhaliev, K.S., Gozhina, O.V. and Trefilova, I.N. (2003) New Fused Thiazepines. Izvestiya Vysshikh Uchebnykh Zavedenii, Khimiya i Khimicheskaya Tekhnologiya, 46, 12-14.
- Dong, C.K., Urgaonkar, S., Cortese, J.F., Gamo, F.J., Garcia-Bustos, J.F., Lafuente, M.J., Patel, V., Ross, L., Coleman, B.I., Derbyshire, e.R., Clish, C.B., Serrano, A.e., Cromwell, M., Barker, R.H., Dvorin, J.D., Duraisingh, M.T., Wirth, D.F., Clardy, J., and Mazitschek, R. (2011) Identification and Validation of Tetracyclic Benzothiazepines as Plasmodium falciparum Cytochrome bc1 Inhibitors. Chemistry & Biology, 18, 1602-1610. https://doi.org/10.1016/j.chembiol.2011.09.016
- Boyom, F.F., Fokou, P.V.T., Tchokouaha, L.R.Y., Spangenberg, T., Mfopa, A.N., Kouipou, R.M.T., Mbouna, C.J., Donfack Donkeng, V.F. and Zollo, P.H.A. (2014) Repurposing the Open Access Malaria Box to Discover Potent Inhibitors of Toxoplasma gondii and entamoeba histolytica. Antimicrobial Agents and Chemotherapy, 58, 5848-5854. https://doi.org/10.1128/AAC.02541-14
- García, J.J.S., Hernández-Suzan, A.D., Martínez-Klimova, e., Flores-Alamo, M., Apan, T.R. and Klimova, e.I. (2017) “Anti-Michael” and Michael Additions in the Reactions of 2-Arylmethyliden-1,3-Indandiones with 2-Aminothiophenol. International Journal of Organic Chemistry, 7, 57-81. https://doi.org/10.4236/ijoc.2017.71006
- Fetzer, C., Korotkov, V.S., Thanert, R., Lee, K.M., Neuenschwander, M., von Kries, J.P., Medina, e., and Sieber, S.A. (2017) A Chemical Disruptor of the ClpX Chaperone Complex Attenuates the Virulence of Multidrug-Resistant Staphylococcus aureus. Angewandte Chemie International edition, 56, 15746-15750. https://doi.org/10.1002/anie.201708454
- Haeussler, K., Fritz-Wolf, K., Reichmann, M., Rahlfs, S. and Becker, K. (2018) Characterization of Plasmodium falciparum 6-Phosphogluconate Dehydrogenase as an Antimalarial Drug Target. Journal of Molecular Biology, 430, 4049-4067. https://doi.org/10.1016/j.jmb.2018.07.030
- Goldfarb, D.S. (2009) Method Using Lifespan-Altering Compounds for Altering the Lifespan of eukaryotic Organisms, and Screening for Such Compounds. US Patent No. 20090163545 A1 20090625.
- Fetzer, C., Korotkov, V. and Sieber, S. (2018) Preparation of ClpX Inhibitory Compounds Useful for the Treatment of Multidrug-Resistant Staphylococcus aureus and Leukemia. PCT Int. Appl., WO 2018114965 A1 20180628.
- Crane, S. (2019) Inhibitors of Polynucleotide Repeat-Associated RNA Foci and Uses Thereof for Treating Diseases. Can. Pat. Appl., CA 2984073 A1 20190427.