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Updated: Apr 9, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Structure-Activity Relationships of 1,2-Disubstituted Benzimidazoles: Selective Inhibition of Heme Oxygenase-2
Xianqi Kong1, Dragic Vukomanovic2, Kanji Nakatsu2
1Department of Chemistry, Queen's University, Kingston, ON K7L 3N6 (Canada).
Abstract:
Devising ways to up- or down-regulate heme oxygenase activity is attracting much interest as a strategy for the treatment of a variety of disorders. With a view of obtaining compounds that exhibit high potency and selectivity as inhibitors of the heme oxygenase-2 (HO-2) isozyme (constitutive) relative to the heme oxygenase-1 (HO-1) isozyme (inducible), several 1,2-disubstituted 1H-benzimidazoles were designed and synthesized. Specifically, analogues were synthesized in which the C2 substituent was the following: (1H-imidazol-1-yl)methyl, (N-morpholinyl)methyl, cyclopentylmethyl, cyclohexylmethyl, or (norborn-2-yl)methyl. Compounds with the cyclic system in the C2 substituent being a carbocyclic ring, especially cyclohexyl or norborn-2-yl, and the N1 substituent being a ring-substituted benzyl group, especially 4-chlorobenzyl or 4-bromobenzyl, best exhibited the target criteria of high potency and selectivity toward inhibition of HO-2. The new candidates should be useful pharmacological tools and may have therapeutic applications.
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