Background:
Benzimidazole (albendazole), imidazothiazole (levamisole) and imidazole (euconazole)
are used in chemotherapy of helminthosis and mycosis respectively, with central nervous system
(CNS) side effects. But only a limited number of azole groups are used clinically in the treatment of CNS
diseases, which are on increase and could not be cured permanently. Due to increased incidence of more
challenging new CNS diseases, there is a need for the synthesis of more potent CNS drugs.
Methods:
Hence, literature studies were carried out for the identification of common pathways for the
synthesis of the three groups of compounds, their CNS properties and the possibility of modifying them to
potent CNS drugs.
Results:
Findings have shown that gloxal with formaldehyde in the presence of ammonia can be converted
into imidazole, imidazothiazole and benzimidazole via distillation, condensation, alkylation, acylation,
oxidation, cyclization, sulphation and amidation. However, agents such as phosphorus pentoxide, ethanolic
potassium hydroxide, sodium hypochlorite, sodium hexafluroaluminate, aniline, calcium acetate,
calcium benzoate, sodium hydroxide, aromatic aldehydes, bromoketones, alpha dicarbonyl compounds
among others are used as reagents. The furan ring(s) may have a strong capability of penetrating CNS for
the treatment of neurological disorders. The products from the three groups have agonistic, antagonistic,
mixed agonistic and mixed antagonistic depressant and stimulant activities due to the presence of
heteroatoms such as nitrogen, oxygen and sulphur. Imidazole may be the most potent with best characteristics
of CNS penetrability and activity followed by imidazothiazole and benzimidazole.
Conclusion:
Azole group is common to all the three classes and may be responsible for some of their CNS
effects. The resultant compounds could act via all neurotransmitters, voltage and ligand-gated ion channels
and may be chiral.