Imidazo[1,2-a] pyridines are a popular structural motif with therapeutic applications for antibacterial, antiviral and as inhibitors of phosphoinositide 3-kinase and angiogenesis.1,2,3,4 . In a logical extension of the unique collection of the Adesis orthogonally substituted pyridines, we have introduced orthogonally-functionalized imidazo[1,2-a]pyridine building blocks (Table 1).
We have shown remarkable ability to control the substitution at positions 5,6,7, and 8 on this heterocycle. With these advanced materials, differential reaction techniques (e.g., Metal-Halogen-Exchange or Pd cross coupling reactions) can be easily employed to quickly generate a series of qualified targets (Figure 1).
Adesis has also extended its Catalog to include electrophilic halogenations at the 3 position. It can be further envisioned that differential reactivity of these positions will allow for inclusion of novel functional groups and efficient access to pharmaceutically relevant agents (Figure 2).
In conclusion, Adesis' program to design and synthesize novel imidazo[1,2-a]pyridines has also enabled scale-ups to multi-kilogram levels. In our hands these compounds can be easily functionalized at each position for efficient generation of regio-isomers and advanced scaffolds. In the near future Adesis will leverage its experience in heterocyclic chemistry to introduce well over 100 new compositions of matter in this family.
1) Koubachi, J.; El Kazzouli, S.; Berteina-Raboin, S.; Mouaddib, A.; Guillaumet, G.; Journal of Organic Chemistry, 2007, 72, 7650-7655.
2) Kim, O.; Jeoung, Y.; Lee, H.; Hong, S.; Hong, S. Journal of Medicinal Chemistry, 2011, 54, 2455-2466.
3) Stec, M.; Andrews, K.; Booker, S.; Caenepeel, S.; Freeman, D.; Jinag, J.; Liao, H.; McCarter, J.; Mullady, E.; San Miguel, T.; Subramanian, R.; Tamayo, N.; Wang, L.; Yang, K.; Zalameda, L.; Zhang, N.; Hughes, P.; Norman, M.; Journal of Medicinal Chemistry, 2011, 54, 5174-5184.
4) Enguehard, C.; Renou, J.; Collot, V.; Hervet, M.; Rault, S.; Gueiffer, A.; Journal of Organic Chemistry, 2000, 65, 6572-6575.