Conversion of Benzimidazoles, Imidazothiazoles and Imidazoles into more Potent Central Nervous System Acting Drugs

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Author(s): Saganuwan Alhaji Saganuwan*.

Journal Name: Central Nervous System Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

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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 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 need for synthesis of more potent CNS drugs.

Methods: Hence, literatures were searched for identification of common pathways for synthesis of the three groups of the compounds, their CNS properties and possibility of modifying them to potent CNS drugs.

Results: Findings have shown that gloxal with formaldehyde in the presence of ammonia can be converted to 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 strong ability of penetrating CNS for treatment of neurological disorders. The products from the three groups have agonistic, antagonistic, mixed agonistic and mixed antagonistic depressant and stimulant activities due to 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.

Keywords: Azole, brain, drug, medicinal chemistry, neuropsychopharmacologAzole, neuropsychopharmacology

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(E-pub Ahead of Print)
DOI: 10.2174/1871524919666190621160323