title: N-[1-Aryl-2-(1-imidazolo)ethyl]-guanidine derivatives as potent inhibitors of the bovine mitochondrial F1F0 ATP hydrolase.
abstract: 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.
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb, Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: Karnail S
authors.initials: KS
authors.lastname: Atwal
authors.forename: Saleem
authors.initials: S
authors.lastname: Ahmad
authors.forename: Charles Z
authors.initials: CZ
authors.lastname: Ding
authors.forename: Philip D
authors.initials: PD
authors.lastname: Stein
authors.forename: John
authors.initials: J
authors.lastname: Lloyd
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Hamann
authors.forename: David W
authors.initials: DW
authors.lastname: Green
authors.forename: Francis N
authors.initials: FN
authors.lastname: Ferrara
authors.forename: Paulina
authors.initials: P
authors.lastname: Wang
authors.forename: W Lynn
authors.initials: WL
authors.lastname: Rogers
authors.forename: Lidia M
authors.initials: LM
authors.lastname: Doweyko
authors.forename: Arthur V
authors.initials: AV
authors.lastname: Miller
authors.forename: Sharon N
authors.initials: SN
authors.lastname: Bisaha
authors.forename: Joan B
authors.initials: JB
authors.lastname: Schmidt
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Yost
authors.forename: Hsi-Jung
authors.initials: HJ
authors.lastname: Lan
authors.forename: Cort S
authors.initials: CS
authors.lastname: Madsen
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006146:Guanidines / Q000138:chemical synthesis / Q000494:pharmacology*; D008928:Mitochondria / Q000201:enzymology*; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D000255:Adenosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases