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

Nadège Hamon; Magdalena Slusarczyk; Michaela Serpi; Jan Balzarini; Christopher McGuigan

doi:10.1016/j.bmc.2014.12.039

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

Bioorg Med Chem. 2015 Feb 15;23(4):829-38. doi: 10.1016/j.bmc.2014.12.039. Epub 2014 Dec 25.

Authors

Nadège Hamon¹, Magdalena Slusarczyk¹, Michaela Serpi¹, Jan Balzarini², Christopher McGuigan³

Affiliations

¹ School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, King Edward VII Avenue, Cardiff CF10 3NB, UK.
² Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
³ School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, King Edward VII Avenue, Cardiff CF10 3NB, UK. Electronic address: [email protected].

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.

Keywords: 2-Deoxy-d-ribose-1-phosphate; Anticancer; Antiviral; Carbasugar; Phosphoramidate; Prodrugs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amides / chemical synthesis
Amides / chemistry*
Amides / pharmacology*
Anti-HIV Agents / chemical synthesis
Anti-HIV Agents / chemistry*
Anti-HIV Agents / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Carbasugars / chemical synthesis
Carbasugars / chemistry
Carbasugars / pharmacology
Cell Line, Tumor
HIV / drug effects
HIV Infections / drug therapy
Humans
Neoplasms / drug therapy
Phosphoric Acids / chemical synthesis
Phosphoric Acids / chemistry*
Phosphoric Acids / pharmacology*
Prodrugs
Ribosemonophosphates / chemical synthesis
Ribosemonophosphates / chemistry*
Ribosemonophosphates / pharmacology*

Substances

Amides
Anti-HIV Agents
Antineoplastic Agents
Carbasugars
Phosphoric Acids
Prodrugs
Ribosemonophosphates
2-deoxyribose 1-phosphate
phosphoramidic acid