Title |
Design and Synthesis of α‑Carboxy Nucleoside Phosphonate Analogues and Evaluation as HIV‑1 Reverse Transcriptase-Targeting Agents
|
---|---|
Published in |
Journal of Organic Chemistry, January 2015
|
DOI | 10.1021/jo502549y |
Pubmed ID | |
Authors |
Sarah J. Keane, Alan Ford, Nicholas D. Mullins, Nuala M. Maguire, Thibaut Legigan, Jan Balzarini, Anita R. Maguire |
Abstract |
The synthesis of the first series of a new class of nucleoside phosphonate analogues is described. Addition of a carboxyl group at the α position of carbocyclic nucleoside phosphonate analogues leads to a novel class of potent HIV reverse transcriptase (RT) inhibitors, α-carboxy nucleoside phosphonates (α-CNPs). Key steps in the synthesis of the compounds are Rh-catalyzed O-H insertion and Pd-catalyzed allylation reactions. In cell-free assays, the final products are markedly inhibitory against HIV RT and do not require phosphorylation to exhibit anti-RT activity, which indicates that the α-carboxyphosphonate function is efficiently recognized by HIV RT as a triphosphate entity, an unprecedented property of nucleoside monophosph(on)ates. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Russia | 1 | 3% |
Italy | 1 | 3% |
Unknown | 27 | 93% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 7 | 24% |
Professor | 3 | 10% |
Professor > Associate Professor | 3 | 10% |
Student > Master | 3 | 10% |
Student > Ph. D. Student | 3 | 10% |
Other | 4 | 14% |
Unknown | 6 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Chemistry | 20 | 69% |
Unspecified | 1 | 3% |
Veterinary Science and Veterinary Medicine | 1 | 3% |
Unknown | 7 | 24% |