N-[1-aryl-2-(1-imidazolo)ethyl]-guanidine derivatives as potent inhibitors of the bovine mitochondrial F1F0 ATP hydrolase

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N-[1-aryl-2-(1-imidazolo)ethyl]-guanidine derivatives as potent inhibitors of the bovine mitochondrial F1F0 ATP hydrolase

ATWAL, Karnail S; AHMAD, Saleem; DOWEYKO, Lidia M; MILLER, Arthur V; BISAHA, Sharon N; SCHMIDT, Joan B; LING LI; YOST, Kenneth J; LANE, Hsi-Jung; MADSEN, Cort S; DING, Charles Z; STEIN, Philip D; LLOYD, John; HAMANN, Lawrence G; GREEN, David W; FERRARA, Francis N; WANG, Paulina; ROGERS, W. Lynn

Bioorganic & medicinal chemistry letters, 02/2004, Volume: 14, Issue: 4

Journal Article

A series of substituted guanidine derivatives were prepared and evaluated as potent and selective inhibitors of mitochondrial F(1)F(0) ATP hydrolase. The initial thiourethane derived lead molecules possessed intriguing in vitro pharmacological profiles, though contained moieties considered non-drug-like. Analogue synthesis efforts led to compounds with maintained potency and superior physical properties. Small molecules in this series which potently and selectivity inhibit ATP hydrolase and not ATP synthase may have utility as cardioprotective agents.

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