Abstract
Several imidazole-dioxolane compounds were synthesized and evaluated as novel inhibitors of heme oxygenase (HO). These compounds, which include (2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-methyl-1,3-dioxolane (1) hydrochloride, are structurally distinct from metalloporphyrin HO inhibitors and lack the aminothiophenol moiety of azalanstat. They were found to be highly selective for the HO-1 isozyme (stress induced) and had substantially less inhibitory potency toward HO-2, the constitutive isozyme. These imidazole-dioxolane compounds are the first of their type known to exhibit this isozyme-selective HO inhibition.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cytosol / drug effects
-
Cytosol / enzymology
-
Dioxolanes / chemical synthesis*
-
Dioxolanes / chemistry
-
Dioxolanes / pharmacology
-
Heme Oxygenase (Decyclizing) / antagonists & inhibitors*
-
Heme Oxygenase-1 / antagonists & inhibitors*
-
Humans
-
Imidazoles / chemical synthesis*
-
Imidazoles / chemistry
-
Imidazoles / pharmacology
-
In Vitro Techniques
-
Isoenzymes / antagonists & inhibitors
-
Microsomes / drug effects
-
Microsomes / enzymology
-
Rats
-
Rats, Sprague-Dawley
-
Stereoisomerism
-
Structure-Activity Relationship
Substances
-
2-(2-(4-chlorophenyl)ethyl)-2-((1H-imidazol-1-yl)methyl)-4-methyl-1,3-dioxolane
-
Dioxolanes
-
Imidazoles
-
Isoenzymes
-
Heme Oxygenase (Decyclizing)
-
Heme Oxygenase-1
-
heme oxygenase-2