162756-98-1Relevant articles and documents
Synthesis and biological evaluation of 6-(alkyn-1-yl)furo[2,3-d]pyrimidin- 2(3H)-one base and nucleoside derivatives
Robins, Morris J.,Miranda, Karl,Rajwanshi, Vivek K.,Peterson, Matt A.,Andrei, Graciela,Snoeck, Robert,De Clercq, Erik,Balzarini, Jan
, p. 391 - 398 (2006)
Derivatives of the 2′-deoxynucleoside of furo[2,3-d]pyrimidin-2(3H)- one with long-chain alkyl (or 4-alkylphenyl) substituents at C6 exhibit remarkable anti-VZV (varicella-zoster virus) potency and selectivity, and analogous 2′,3′-dideoxynucleoside derivatives show anti-HCMV (human cytomegalovirus) activity. We now report a synthetic approach that enables the preparation of long-chain 6-(alkyn-1-yl)furo[2,3-d]pyrimidin-2(3H)-ones in which the rodlike acetylene spacer replaces the 4-substituted-phenyl ring at C6. Analogues with methyl, β-D-ribofuranosyl, β-D-arabinofuranosyl, and 2-deoxy-β-D-erythro-pentofuranosyl substituents at N3 have been prepared. Long-chain derivatives at C6 in the 2′-deoxynucleoside series showed virus-encoded nucleoside kinase-sensitive anti-VZV activity. Surprisingly, 3-methyl-6-(octyn-1-yl)furo[2,3-d]-pyrimidin-2(3H)-one (prepared as a negative anti-VZV test control) exhibited anti-HCMV activity, which supports the possibility of development of non-nucleoside anti-HCMV agents originating from uncomplicated derivatives of such bicyclic ring systems.
