Recent developments on triazole nucleus in anticonvulsant compounds: a review

Abstract

Epilepsy is one of the common diseases seriously threatening life and health of human. More than 50 million people are suffering from this condition and anticonvulsant agents are the main treatment. However, side effects and intolerance, and a lack of efficacy limit the application of the current anticonvulsant agents. The search for new anticonvulsant agents with higher efficacy and lower toxicity continues to be the focus and task in medicinal chemistry. Numbers of triazole derivatives as clinical drugs or candidates have been frequently employed for the treatment of various types of diseases, which have proved the importance of this heterocyclic nucleus in drug design and discovery. Recently many endeavours were made to involve the triazole into the anticonvulsants design, which have brought lots of active compounds. This work is an attempt to systematically review the research of triazole derivatives in the design and development of anticonvulsant agents during the past two decades.

Keywords: Epilepsy; MES; anticonvulsant; scPTZ; triazole.

Figure 1.

The structures of triazole.

Scheme 1.

The introducing method of triazole for 1-substituted-1,2,4-triazoles.

Figure 2.

Structures of 1-substituted-1,2,4-triazoles (1–4).

Figure 3.

Structures of 1-substituted-1,2,4-triazoles (5–12).

Figure 4.

Structures of 1-substituted-1,2,4-triazoles (13–15).

Scheme 2.

The introducing method of triazole for 4-Substituted-1,2,4-triazoles.

Figure 5.

Structures of 4-substituted-1,2,4-triazoles (16–25).

Figure 6.

Ring-opening derivatives of alprazolam and triazolam (26–32).

Figure 7.

Polysubstituted-4H-1,2,4-triazoles (33–42).

Scheme 3.

The prepared methods of triazolones and triazolthiones.

Figure 8.

Substituted triazolones (43–47).

Figure 9.

Substituted triazolones (48–55).

Figure 10.

Substituted triazolthiones (56–63).

Figure 11.

Substituted triazolthiones (64–70).

Figure 12.

Substituted triazolthiones (71–78).

Scheme 4.

The classical preparation method of fused-triazoles.

Figure 13.

Triazolopyrimidines, triazolopyridazines, triazolopyridines, and triazolopyrazines (79–86).

Figure 14.

Triazolothiazoles, triazolothiadiazines, triazolothiadiazoles, and triazolothiazepines (87–94).

Scheme 5.

The structure-activity diagram of the triazolothiadiazines.

Figure 15.

Triazoloquinolines (95–99) with anticonvulsant activity.

Figure 16.

Triazoloquinolines (100–105) with anticonvulsant activity.

Figure 17.

Triazoloquinazolines (106–114) with anticonvulsant activity.

Figure 18.

Triazolophthalazine and quinoxalines (115–122) with anticonvulsant activity.

Figure 19.

Triazolobenzothiazines and triazolobenzothiazoles (123 and 124).

Figure 20.

Triazolebenzodiazepines (125–130).

Figure 21.

The structures of RL 218 and RL 236 and their hydrolyzate RL 214.

Figure 22.

Tricyclic fused-triazoles containing 7-membered ring (131–136).

Figure 23.

Tricyclic fused-triazoles containing 7-membered ring (137–140).

Figure 24.

Tetracyclic fused-triazoles (141–143).

Scheme 6.

The structure-activity diagram of the triazoloquinolines.

Figure 25.

Fused-triazolones and fused-triazolthiones (144–153).

Figure 26.

1,2,3-Triazoles with anticonvulsant activity (154–159).