Multicomponent chemistry in the synthesis of carbonic anhydrase inhibitors

Figures & data

Scheme 1. Multicomponent synthesis of aminocyanopyrazoles 4.

Scheme 2. Synthesis of N-tosyl-substituted aminocyanopyrazoles 5.

Scheme 3. Preparation of N-sulfonamide derivatives 6.

Figure 1. Most potent CA inhibitors reported by Allouche et al16.

Scheme 4. Three-component synthesis of 1,3-dicarbonyl derivatives of sulfanilamide (8)*.

Figure 2. Most potent inhibitors of hCA I and hCA II, respectively, reported by Dimirci et al¹⁹.

Scheme 5. Preparation of sulfonamide containing chromone derivatives 11.

Scheme 6. Preparation of sulfonamide containing chromone derivatives 12.

Figure 3. Biological activity data for the lead compound 12 reported by Awadallah et al²¹.

Scheme 7. Preparation of 1,4-dihydropyrimidinone substituted diaryl(thio)ureas 14.

Figure 4. Inhibitory properties of exemplary urea and thiourea derivatives reported by Celic et al22.

Scheme 8. Preparation of novel 1,4-dihydropyrimidine derivatives 15–19.

Figure 5. IC₅₀’s against hCA I for selected weak inhibitors reported by Celik et al.

Scheme 9. Preparation of phtalazine derivatives 20, 21, 22 and 23.

Figure 6. Most active compounds of 28 phtalazine derivatives reported by Beber et al24,25.

Figure 7. Leading compound reported by Suthar et al28.

Scheme 10. Synthesis of arylthiazolidine-substituted benzenesulfonamides 24.

Scheme 11. Preparation of acridine-based sulfonamides 25 via the Hantzsch reaction.

Figure 8. Examples of acridine monosulfonamide derivatives.

Scheme 12. Acridine derivatives 28–30.

Scheme 13. Preparation of 31 and bisacridines 32 via the Hantzsch reaction.

Figure 9. Most potent representatives of 31 and 32 and their K_i’s against hCA I, II and VII.

Scheme 14. Synthesis of 1,4-dihydropyridine-containing benzenesulfonamide derivatives 34.

Scheme 15. Multicomponent synthesis of 2-amino-nicotinonitriles 35 and 36.

Scheme 16. Preparation of quinoline and pyrimidoquinoline sulfonamide derivatives 38–40.

Scheme 17. Examples of derivatization of 2-amino-3-cyano-1,4-dihydropyridine moiety in sulfonamide 41.

Scheme 18. Synthesis of 2-aminonicotinonitrile 48 via a Hantzsch-type reaction.

Scheme 19. Derivatization of 48.

Scheme 20. Further derivatization of core building block 48.

Figure 10. Most active Mannich adducts, reported by Hartman et al39.

Scheme 21. Aminomethylation of furan and thiophene sulfonamide derivatives (no yields reported).

Scheme 22. Preparation and K_i’s of isatin Mannich bases 61–63.

Scheme 23. Aminomethylation of 3,4-dimethylphenole.

Figure 11. Mannich adducts reported by Chow et al42.

Figure 12. Percentage of inhibition data for progenitor compound 67 and its most potent Mannich derivatives 68–69.

Scheme 24. Mannich aminomethylation in ortho- or para-position of thymol.

Figure 13. Inhibition percentage of most potent 2- and 4-methylamino derivatives of thymol.

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