Acyclic analogues of pyrazofurin: syntheses and antiviral evaluation.
Acyclic analogues of pyrazofurin, including 4-hydroxy-3(5)-[( 2-hydroxy-1-(hydroxymethyl)-ethoxy]methyl)-1H-pyrazole-5 (3)-carboxamide (36) and 4-hydroxy-3(5)-[(2-hydroxyethoxy)methyl]-1H-pyrazole-5(3)-carboxamide (27), that possess the side chains of ganciclovir and acyclovir, respectively, were prepared by heating methyl 4-acetoxy-1-acetyl-3-bromomethyl-1H-pyrazole-5-carboxylate (15) and sodium acetate in the requisite alcohols or, for 36, with the sodium alkoxide in dry tetrahydrofuran. These analogues have no antiviral activity, except 4-hydroxy-3(5)-[(3-hydroxypropoxy)methyl]-1H-pyrazole-5(3)-carboxamide (28), which exhibited slight activity against human cytomegalovirus.
Comber
R N
RN
Southern Research Institute, Organic Chemistry Research Department, Birmingham, Alabama 35255.
Gray
R J
RJ
Secrist
J A
JA
D000577:Amides; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D015394:Molecular Structure; D011720:Pyrazoles; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012266:Ribose; D014780:Viruses / Q000187:drug effects
D000577:Amides; D000998:Antiviral Agents; D011720:Pyrazoles; D012263:Ribonucleosides; C002997:pyrazofurin; D012266:Ribose