Synthesis and evaluation of azalanstat analogues as heme oxygenase inhibitors

Jason Z Vlahakis; Robert T Kinobe; Raymond J Bowers; James F Brien; Kanji Nakatsu; Walter A Szarek

doi:10.1016/j.bmcl.2004.12.075

Synthesis and evaluation of azalanstat analogues as heme oxygenase inhibitors

Bioorg Med Chem Lett. 2005 Mar 1;15(5):1457-61. doi: 10.1016/j.bmcl.2004.12.075.

Authors

Jason Z Vlahakis¹, Robert T Kinobe, Raymond J Bowers, James F Brien, Kanji Nakatsu, Walter A Szarek

Affiliation

¹ Departments of Chemistry, Queen's University, Kingston, ON K7L 3N6, Canada.

PMID: 15713406
DOI: 10.1016/j.bmcl.2004.12.075

Abstract

Several analogues based on the lead structure of azalanstat were synthesized and evaluated as novel inhibitors of heme oxygenase (HO). A number of these compounds, which are structurally distinct from metalloporphyrin HO inhibitors, were found to be selective for the HO-1 isozyme (stress induced), and had substantially less inhibitory activity on HO-2, the constitutive isozyme.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aniline Compounds / chemical synthesis*
Aniline Compounds / pharmacology*
Animals
Drug Evaluation, Preclinical
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Heme Oxygenase (Decyclizing) / antagonists & inhibitors*
Heme Oxygenase-1
Molecular Conformation
Rats
Structure-Activity Relationship
Sulfides / chemical synthesis*
Sulfides / pharmacology*

Substances

Aniline Compounds
Enzyme Inhibitors
Sulfides
azalanstat
Heme Oxygenase (Decyclizing)
Heme Oxygenase-1
heme oxygenase-2