title: New acyloxy nitroso compounds with improved water solubility and nitroxyl (HNO) release kinetics and inhibitors of platelet aggregation.
abstract: New acyloxy nitroso compounds, 4-nitrosotetrahydro-2H-pyran-4-yl 2,2,2-trichloroacetate and 4-nitrosotetrahydro-2H-pyran-4-yl 2,2-dichloropropanoate were prepared. These compounds release HNO under neutral conditions with half-lives between 50 and 120min, identifying these HNO donors as kinetically intermediate to the much slower acetate derivative and the faster trifluoroacetic acid derivative. These compounds or HNO-derived from these compounds react with thiols, including glutathione, thiol-containing enzymes and heme-containing proteins in a similar fashion to other acyloxy nitroso compounds. HNO released from these acyloxy nitroso compounds inhibits activated platelet aggregation. These acyloxy nitroso compounds augment the range of release for this group of HNO donors and should be valuable tools in the further study of HNO biology.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
authors.forename: Heba A H
authors.initials: HA
authors.lastname: Mohamed
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Aziz
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
authors.forename: Gamal El-Din A A
authors.initials: Gel-D
authors.lastname: Abuo-Rahma
authors.affiliation: Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, United States. Electronic address: kingsb@wfu.edu.
authors.forename: S Bruce
authors.initials: SB
authors.lastname: King
mesh_terms: D006801:Humans; D015394:Molecular Structure; D009589:Nitrogen Oxides / Q000737:chemistry*; D009603:Nitroso Compounds / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*
chemical_list: D009589:Nitrogen Oxides; D009603:Nitroso Compounds; C039900:nitroxyl
keywords: Acyloxy nitroso compounds; Heme proteins; Nitroxyl; Platelet aggregation; Thiols