title: Synthesis and biological evaluation of phosphoramidate prodrugs of two analogues of 2-deoxy-d-ribose-1-phosphate directed to the discovery of two carbasugars as new potential anti-HIV leads.
abstract: 2-Deoxy-α-d-ribose-1-phosphate is of great interest as it is involved in the biosynthesis and/or catabolic degradation of several nucleoside analogues of biological and therapeutic relevance. However due to the lack of a stabilising group at its 2-position, it is difficult to synthesize stable prodrugs of this compound. In order to overcome this lack of stability, the synthesis of carbasugar analogues of 2-deoxyribose-1-phosphate was envisioned. Herein the preparation of a series of prodrugs of two carbocyclic analogues of 2-deoxyribose-1-phosphate using the phosphoramidate ProTide technology, along with their biological evaluation against HIV and cancer cell proliferation, is reported.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, King Edward VII Avenue, Cardiff CF10 3NB, UK.
authors.forename: Nadège
authors.initials: N
authors.lastname: Hamon
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, King Edward VII Avenue, Cardiff CF10 3NB, UK.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Slusarczyk
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, King Edward VII Avenue, Cardiff CF10 3NB, UK.
authors.forename: Michaela
authors.initials: M
authors.lastname: Serpi
authors.affiliation: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, King Edward VII Avenue, Cardiff CF10 3NB, UK. Electronic address: mcguigan@cardiff.ac.uk.
authors.forename: Christopher
authors.initials: C
authors.lastname: McGuigan
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D054329:Carbasugars / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D006678:HIV / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D010756:Phosphoric Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011355:Prodrugs; D012267:Ribosemonophosphates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000577:Amides; D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D054329:Carbasugars; D010756:Phosphoric Acids; D011355:Prodrugs; D012267:Ribosemonophosphates; C031302:2-deoxyribose 1-phosphate; C011067:phosphoramidic acid
keywords: 2-Deoxy-d-ribose-1-phosphate; Anticancer; Antiviral; Carbasugar; Phosphoramidate; Prodrugs