Exploring the untapped pharmacological potential of imidazopyridazines

Abstract

Imidazopyridazines are fused heterocycles, like purines, with a pyridazine ring replacing the pyrimidine ring in purines. Imidazopyridazines have been primarily studied for their kinase inhibition activity in the development of new anticancer and antimalarial agents. In addition to this, they have also been investigated for their anticonvulsant, antiallergic, antihistamine, antiviral, and antitubercular properties. Herein, we review the background and development of different imidazopyridazines as potential pharmacological agents. Moreover, the scope of this relatively less charted heterocyclic scaffold is also highlighted.

Fig. 1. Drugs with imidazopyrimidine (purine) and imidazopyridazine rings (see inset).

Fig. 2. Different imidazopyridazine rings.

Fig. 3. Some synthetic routes to imidazo[1,2-b]pyridazines.

Fig. 4. Imidazopyridazine 9 as anticancer agents and subsequent development.

Fig. 5. Imidazopyridazines as selective pan-TRK inhibitors: synthesis of active inhibitor 12.

Fig. 6. Imidazopyridazines as Mps1 (TTK) kinase inhibitors: synthesis of active inhibitor 17.

Fig. 7. Imidazopyridazines as Pim kinases and acetylcholinesterase inhibitors.

Fig. 8. Imidazopyridazines as antiproliferative agent.

Fig. 9. Imidazopyridazines as PfPK7 kinase inhibitor and antimalarial agent. Synthesis of active compound 32.

Fig. 10. Imidazopyridazines as PfCDPK7 kinase inhibitor and antiplasmodial agent.

Fig. 11. Imidazopyridazines as antiplasmodial agent. Synthesis of active compound 39.

Fig. 12. Development of potent antiplasmodial imidazopyridazine 44.

Fig. 13. Imidazopyridazines as antisense and antihistamine agent.

Fig. 14. Imidazopyridazines as antiviral and anti-tubercular agents.

Fig. 15. Imidazopyridazine moiety in approved and investigational drugs.

M. Shaheer Malik

Saleh A. Ahmed