THE SYNTHESIS OF ANTI RESTRICTED PYRIMIDINE ACYCLIC NUCLEOSIDES AND THEIR CORRESPONDING CARBON 6 PYRIMIDINE ACYCLIC NUCLEOSIDES AS POTENTIAL ANTIVIRAL AGENTS

Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

THE SYNTHESIS OF ANTI RESTRICTED PYRIMIDINE ACYCLIC NUCLEOSIDES AND THEIR CORRESPONDING CARBON 6 PYRIMIDINE ACYCLIC NUCLEOSIDES AS POTENTIAL ANTIVIRAL AGENTS

Diss Abstr Int [B]; 52(3):1453 1991. Unique Identifier : AIDSLINE ICDB/92679013
Hsu L; Univ. of Michigan

Abstract: The goal of this thesis was to synthesize certain restricted pyrimidine acyclic nucleosides (R(anti)-PANs) and their corresponding C6-PANs for their potential as a source of antiviral agents and to possibly afford insight into the conformation of nucleosides involved in the enzymatic interaction of HSV-TK. Thus, two new classes of compounds, R(anti)-PANs (6,5'-cyclo-5'-deoxy-5-methyl-2',3'-secouridine, 2-substituted pyrimido (1,6-c) (1,3) oxazine, 1-substituted pyrimido (1,6-c) (1,3) oxazine, 1-substituted pyrimido (1,6-c) (1,3) oxazepine) and their corresponding C6-PANs were prepared by multiple step synthesis. From computerized molecular modeling, it was observed that the dihedral angles of the oxazine derivatives were closer to that observed for thymidine than found for the oxazepine derivative. The C6-PAN derivative containing a 2-(1, 2, 3-trihydroxy)propylmethyl side chain at C6 of the pyrimidine could be superimposed very well with thymidine. Evaluation of the target compounds for cytotoxicity (L1210 leukemia cell) and inhibitory activity against herpes simplex virus type 1, human cytomegalovirus and human immunodeficiency virus (HIV) revealed that all compounds except 8-amino-2,2-bis(hydroxymethyl)-9-methyl-(1H, 2H, 4H)-pyrimido (1,6-c) (1,3) oxazin-6-one (2.12a) were inactive. Compound (2.12a) showed a moderate inhibitory activity against HIV. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD91-24025).

Keywords: *Antiviral Agents/CHEMICAL SYNTHESIS Cell Survival/DRUG EFFECTS Cytomegalovirus/DRUG EFFECTS HIV/DRUG EFFECTS Leukemia L1210/PATHOLOGY Models, Molecular Pyrimidine Nucleosides/*CHEMICAL SYNTHESIS/PHARMACOLOGY Simplexvirus/DRUG EFFECTS Structure-Activity Relationship Tumor Cells, Cultured/DRUG EFFECTS THESIS

920530
M9250961

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