Benzodiazepine-based selective inhibitors of mitochondrial F1F0 ATP hydrolase

Lawrence G Hamann; Charles Z Ding; Arthur V Miller; Cort S Madsen; Paulina Wang; Philip D Stein; Andrew T Pudzianowski; David W Green; Hossain Monshizadegan; Karnail S Atwal

doi:10.1016/j.bmcl.2003.11.052

Benzodiazepine-based selective inhibitors of mitochondrial F1F0 ATP hydrolase

Bioorg Med Chem Lett. 2004 Feb 23;14(4):1031-4. doi: 10.1016/j.bmcl.2003.11.052.

Authors

Lawrence G Hamann¹, Charles Z Ding, Arthur V Miller, Cort S Madsen, Paulina Wang, Philip D Stein, Andrew T Pudzianowski, David W Green, Hossain Monshizadegan, Karnail S Atwal

Affiliation

¹ Department of Discovery Chemistry, Bristol-Myers Squibb, Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA. lawrence.hamann@bms.com

PMID: 15013017
DOI: 10.1016/j.bmcl.2003.11.052

Abstract

A series of benzodiazepine-based inhibitors of mitochondrial F(1)F(0) ATP hydrolase were prepared and evaluated for their ability to selectively inhibit the enzyme in the forward direction. Compounds from this series showed excellent potency and selectivity for ATP hydrolase versus ATP synthase, suggesting a potentially beneficial profile useful for the treatment of ischemic heart disease.

MeSH terms

Adenosine Triphosphate / metabolism*
Animals
Benzodiazepines / chemical synthesis
Benzodiazepines / pharmacology*
Cattle
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology*
Mitochondria / enzymology*
Mitochondrial Proton-Translocating ATPases / antagonists & inhibitors*
Mitochondrial Proton-Translocating ATPases / metabolism
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Benzodiazepines
Adenosine Triphosphate
Mitochondrial Proton-Translocating ATPases