SYNTHESIS AND ANTIVIRAL EVALUATION OF SUGAR-MODIFIED DERIVATIVES OF THE NUCLEOSIDE ANTIBIOTICS TUBERCIDIN, TOYOCAMYCIN AND SANGIVAMYCIN

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

SYNTHESIS AND ANTIVIRAL EVALUATION OF SUGAR-MODIFIED DERIVATIVES OF THE NUCLEOSIDE ANTIBIOTICS TUBERCIDIN, TOYOCAMYCIN AND SANGIVAMYCIN

Diss Abstr Int [B]; 52(3):1439 1991. Unique Identifier : AIDSLINE ICDB/92679011
Krawczyk SH; Univ. of Michigan

Abstract: The emergence of the AIDS has been followed by an increase in the incidence of infections due to human cytomegalovirus (HCMV). In our search for new and novel classes of compounds as potential inhibitors of HCMV, we have discovered that a class of compounds known as the pyrrolo (2,3-d) pyrimidine nucleosides are potent inhibitors of this virus. This class of nucleosides is exemplified by the naturally occurring nucleoside antibiotics tubercidin, toyocamycin, and sangivamycin. Our efforts toward the discovery of agents which are inhibitory towards HCMV has led us to prepare a variety of sugar and base modified analogs of these three nucleoside antibiotics. The modifications we have made include the synthesis of 2'-deoxy-2'-substituted derivatives of aratoyocamycin and arasangivamycin. The 2' substituents which we have introduced include the chloro, bromo, iodo, fluoro, azido and amino moieties. Additionally, we have prepared the 2',3'-dideoxy and the 2',3'-dideoxy-2',3'-didehydro derivatives of tubercidin, toyocamycin, sangivamycin and 4-desamino-4-oxotoyocamycin. Finally, we have prepared a variety of thiosangivamycin analogs. These analogs include 2'-deoxythiosangivamycin, 3'-deoxythiosangivamycin, 2',3'-dideoxythiosangivamycin, 2',3'-dideoxy-2',3'-didehydrothiosangivamycin, arathiosangivamycin, 2'-deoxy-2'-fluoroarathiosangivamycin and 2'-deoxy-2'-aminoarathiosangivamycin. The antiviral evaluation of some representative analogs revealed that none was more potent and selective than ganciclovir. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD91-24149).

Keywords: Acquired Immunodeficiency Syndrome/COMPLICATIONS *Antibiotics/CHEMICAL SYNTHESIS/THERAPEUTIC USE *Antiviral Agents Cytomegalovirus/DRUG EFFECTS Cytomegalovirus Infections/COMPLICATIONS/DRUG THERAPY Pyrimidine Nucleosides/CHEMICAL SYNTHESIS/*PHARMACOLOGY/ THERAPEUTIC USE Toyocamycin/ANALOGS & DERIVATIVES/CHEMICAL SYNTHESIS/ *PHARMACOLOGY/THERAPEUTIC USE Tubercidin/ANALOGS & DERIVATIVES/CHEMICAL SYNTHESIS/*PHARMACOLOGY/ THERAPEUTIC USE THESIS
920430
M9240943

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