Advanced Functionalized Pyrazines for Applications in Drug Discovery and Materials Science

The pyrazine substructure is present in many biologically and technologically relevant compounds.¹ For example, the pyrazine moiety is found in riboflavin and folic acid, which are members of the vitamin B family. Several pyrazine-based alkaloids have been isolated from marine microorganisms, such as clavulazine 1² and botryllazine A 2³ (Fig. 1). Consequently, a number of total syntheses of the naturally occurring pyrazines have been reported.⁴

Substituted pyrazines are widely used as pharmaceuticals. Today there are 16 approved and ca. 50 experimental pyrazine-based drugs of very different pharmacological actions,⁵ e.g., Pyrazinamide 3 is probably the best known synthetic antimycobacterial agent used for treatment of tuberculosis, whereas Sulfametopyrazine 4 is used for treatment of respiratory and urinary tract infections. Furthermore, many novel functionalized pyrazines are presently involved in drug discovery programs.⁶

Pyrazine-based polymers and other light-responsive materials are of high interest for technological applications.⁷ For example, ladder polymer 5^7b (Fig. 1) was synthesized to be used in optical devices. Additionally, a number of low-bandgap π-conjugated pyrazine polymers have been synthesized for applications in photovoltaic devices.⁸

Figure 1. Examples of natural products, synthetic drugs, and polymers containing the pyrazine fragment

Life Chemicals offers structurally diverse functionalized pyrazine derivatives for applications in drug discovery and materials science. The representative structures are provided below. The full data-set can be obtained upon request at orders@lifechemicals.com.

References

1. Sato, N. In Comprehensive Heterocyclic Chemistry III, Eds. Katritzky, A. R.; Ramsden, C. A.; Scriven, E. F. V.; Taylor, R. J. K. Pergamon, Oxford, 2008. Vol. 8, p. 273.
2. Watanabe, K.; Iguchi, K.; Fujimori, K. Heterocycles 1998, 49, 269.
3. Duran, R.; Zubia, E.; Ortega, M. J.; Naranjo, S.; Salva, J. Tetrahedron 1999, 55, 13225
4. For example, see: (a) Droegemueller, M.; Jautelat, R.; Winterfeldt, E. Angew. Chem. Int. Ed. 1996, 35, 1572. (b) Buron, F.; Ple, N.; Turck, A.; Queguiner, G. J. Org. Chem. 2005, 70, 2616. (c) Singh, P. P.; Aithagani, S. K.; Yadav, M.; Singh, V. P.; Vishwakarma, R. A. J. Org. Chem. 2013, 78, 2639.
5. www.drugbank.ca; accessed in May 2019
6. For recent works, see: (a) Chrovian, C. C.; Soyode-Johnson, A.; Ao, H.; Bacani, J. M.; Carruthers, N. I.; Lord, B.; Nguyen, L.; Rech, J. C.; Wang, Q.; Bhattacharya, A.; Letavic, M. A. ACS Chem. Neurosci., 2016, 7, 490–497. (b) Osborne, J. D.; Matthews, T. P.; McHardy, T. et al. J. Med. Chem. 2016, 59, 5221–5237. (c) Iwai, K.; Yoshida, S.; Yoshimatsu, M.; Aoyama, K.; Kosugi, Y.; Kojima, T.; Morishita, N.; Dougan, D. R.; Snell, G. P.; Imamura, S.; Ishikawa, T. J. Med. Chem. 2013, 56, 1228. (d) Lainchbury, M.; Collins, I. et al. J. Med. Chem. 2012, 55, 10229.
7. (a) Milić, J. V.; Schaack, C.;  Hellou, N.; Isenrich, F.; Gershoni-Poranne, R.; Neshchadin, D.;  Egloff, S.; Trapp, N.; Ruhlmann, L.; Boudon, C.; Gescheidt, G.; Crassous, J.; Diederich, F. J. Phys. Chem. C 2018, 122, 19100–19109. (b) Zhang, C. Y.; Tour, J. M. J. Am. Chem. Soc. 1999, 121, 8783.
8. (a) Tian, Y.-H.; Kertesz, M. Macromolecules 2009, 42, 2309. (b) Yuan, M.-C.; Chiu, M.-Y.; Chiang, C.-M.; Wei, K.-W. Macromolecules 2010, 43, 6270. (c) Zhou, E.; Cong, J.; Yamakawa, S.; Wei, Q.; Nakamura, M.; Tajima, K.; Yang, C.; Hashimoto, K. Macromolecules 2010, 43, 2873.