title: Aminoimidazoles as bioisosteres of acylguanidines: novel, potent, selective and orally bioavailable inhibitors of the sodium hydrogen exchanger isoform-1.
abstract: Inhibition of the sodium hydrogen exchanger isoform-1 (NHE-1) has been shown to limit damage to the myocardium under ischemic conditions in animals. While most known NHE-1 inhibitors are acylguanidines, this report describes the design and synthesis of a series of heterocyclic inhibitors of NHE-1 including aminoimidazoles with undiminished in vitro activity and oral bioavailability.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543, USA. saleem.ahmad@bms.com
authors.forename: Saleem
authors.initials: S
authors.lastname: Ahmad
authors.forename: Khehyong
authors.initials: K
authors.lastname: Ngu
authors.forename: Donald W
authors.initials: DW
authors.lastname: Combs
authors.forename: Shung C
authors.initials: SC
authors.lastname: Wu
authors.forename: David S
authors.initials: DS
authors.lastname: Weinstein
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Bang-Chi
authors.initials: BC
authors.lastname: Chen
authors.forename: Gamini
authors.initials: G
authors.lastname: Chandrasena
authors.forename: Charles R
authors.initials: CR
authors.lastname: Dorso
authors.forename: Mark
authors.initials: M
authors.lastname: Kirby
authors.forename: Karnail S
authors.initials: KS
authors.lastname: Atwal
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002460:Cell Line; D006146:Guanidines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D027682:Cation Transport Proteins; D006146:Guanidines; D007093:Imidazoles; D008565:Membrane Proteins; D020033:Protein Isoforms; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers