Tricyclic etheno analogs of PMEG and PMEDAP: synthesis and biological activity

Katerina Horejsí; Graciela Andrei; Erik De Clercq; Robert Snoeck; Radek Pohl; Antonín Holý

doi:10.1016/j.bmc.2006.07.036

Tricyclic etheno analogs of PMEG and PMEDAP: synthesis and biological activity

Bioorg Med Chem. 2006 Dec 1;14(23):8057-65. doi: 10.1016/j.bmc.2006.07.036. Epub 2006 Aug 10.

Authors

Katerina Horejsí¹, Graciela Andrei, Erik De Clercq, Robert Snoeck, Radek Pohl, Antonín Holý

Affiliation

¹ Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, CZ-166 10 Praha 6, Czech Republic.

PMID: 16904327
DOI: 10.1016/j.bmc.2006.07.036

Abstract

A series of novel 9-substituted (2-(3H-imidazo[1,2-a]purin-3-yl)ethoxy)methylphosphonic and 4-substituted (2-(1H-imidazo[2,1-b]purin-1-yl)ethoxy)methylphosphonic acids as tricyclic etheno analogs of potent antivirals and cytostatics PMEG and PMEDAP was synthesized and evaluated for their biological activity. Most of the compounds showed modest activity against varicella-zoster virus (VZV) and human cytomegalovirus (HCMV) except for (2-(9-oxo-5,9-dihydro-3H-imidazo[1,2-a]purin-3-yl)ethoxy)methylphosphonic acid 8 which proved markedly active against VZV and HCMV. None of the compounds tested exhibited any significant cytostatic effect.

Publication types

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

MeSH terms

Adenine / analogs & derivatives*
Adenine / chemical synthesis
Adenine / pharmacology
Antiviral Agents / chemical synthesis*
Antiviral Agents / pharmacology
Cell Proliferation / drug effects
Cytomegalovirus / drug effects
Guanine / analogs & derivatives*
Guanine / chemical synthesis
Guanine / pharmacology
Herpesvirus 3, Human / drug effects
Humans
Organophosphorus Compounds / chemical synthesis
Organophosphorus Compounds / pharmacology*
Structure-Activity Relationship

Substances

Antiviral Agents
Organophosphorus Compounds
9-((2-phosphonylmethoxy)ethyl)guanine
9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine
Guanine
Adenine