Discover Novel Functionalized Pyrimidines

Pyrimidine derivatives are by far the most important compounds in living organisms. Oxo-pyrimidine-derived cytosine and uracil are subunits of RNA, whereas cytosine and thymine are constituent parts of DNA. The pyrimidine ring is also found in many natural antibiotics that are now actively used in a number of therapies.¹ Along with naturally occurring species, there is a wide range of synthetic pyrimidine derivatives that possess important pharmaceutical or agrochemical properties.² Barbiturates are probably the earliest pyrimidine-based active pharmaceutical ingredients, while fluorouracil is the classic antitumor agent. Moreover, substituted pyrimidines are present in signal transduction inhibitors that are a new class of antitumor agents.³ Marketed antitumor agent imatinib 1 shown in Figure 1 is a representative of the latter drug type. In addition, there are many commercially available antiviral and antibacterial agents containing the substituted pyrimidine unit.⁴ Figure 1 provides some examples of commercially available pyrimidines used as antifungal agents (cyprodinil 2), herbicides (sulfometuron methyl 3), and insecticides (flufenerim 4). Despite a large number of marketed pyrimidine-based drugs and agrochemicals, functionalized pyrimidines are still heavily employed as building blocks in drug discovery programs.⁵

Figure 1. Examples of commercialized drugs and agrochemicals containing the pyrimidine ring.

A representative set of functionalized pyrimidines available from Life Chemicals is given below. The full set of the title structures can be provided upon request at orders@lifechemicals.com.

References:

1. Lagoja, I. M. Chem. Biodiver. 2005, 2, 1.
2. Rewcastle, G. W. 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. 117.
3. Buchdunger, E.; Zimmermann, J.; Mett, H.; Meyer, T.; Muller, M.; Regenass, U.; Lydon, N. B. Proc. Natl. Acad. Sci. USA 1995, 92, 2558.
4. According to www.drugbank.ca (accessed in May 2019) there are 105 pyrimidine-based approved drugs.
5. For recent works, see: (a) Boyer, J.; Arnoult, E.; Médebielle, M.; Guillemont, J.; Unge, J.; Jochmans, D. J. Med. Chem. 2011, 54, 7974. (b) Cha, M. Y.; Lee, K.-O.; Kang, S.-J.; Jung, Y. H.; Song, J. Y.; Choi, K. J.; Byun, J. Y.; Lee, H.-J.; Lee, G. S.; Park, S. B.; Kim, M. S. J. Med. Chem. 2012, 55, 2846. (c) Disch, J. S.; Perni, R. B.; et al. J. Med. Chem. 2013, 56, 3666. (d) Babu, S.; Morrill, C.; Almstead, N. G.; Moon, Y.-C. Org. Lett. 2013, 15, 1882. (e) Gómez-SanJuan, A.; Gamo, A.-M.; Delang, L. et al. ACS Infect. Dis. 2018, 4, 605–619.