Benzodiazepine-based selective inhibitors of mitochondrial F1F0 ATP hydrolase.
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.
Hamann
Lawrence G
LG
Department of Discovery Chemistry, Bristol-Myers Squibb, Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA. lawrence.hamann@bms.com
Ding
Charles Z
CZ
Miller
Arthur V
AV
Madsen
Cort S
CS
Wang
Paulina
P
Stein
Philip D
PD
Pudzianowski
Andrew T
AT
Green
David W
DW
Monshizadegan
Hossain
H
Atwal
Karnail S
KS
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000494:pharmacology*; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D008928:Mitochondria / Q000201:enzymology*; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D001569:Benzodiazepines; D000255:Adenosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases