Synthesis and Biological Evaluation of Carbocyclic Analogs of Lyxofuranosides of 2-Amino-6-Substituted Purines and 2-Amino-6-Substituted-8-Azapurines

Mark L. Peterson, Robert Vince

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25 Scopus citations

Abstract

Carbocyclic analogues of lyxofuranosides of 2-amino-6-substituted-purines and 2-amino-6-substituted-8-azapurines were synthesized from (±)-(1α,2α,3α,5α)-3-amino-5-(hydroxymethyl)-1,2-cyclopentanediol (2) and 2-amino-4,6- dichloropyrimidine (3). The 2-amino-6-chloropurine (8 and 11), the 2,6-diaminopurine (10 and 13), as well as the guanine (9) and 8-azaguanine (12) derivatives were all constructed from the key intermediate (±)-(1α,2α,3α,5α)-3-[(2,5-diamino-6-chloro-4-pyrimidinyl)amino]-5-(hydroxymethyl)-l,2-cyclopentanediol (7) by using established methodology. Compounds 8-13 were evaluated for both antitumor and antiviral activity. None of these materials exhibited appreciable activity against P-388 mouse leukemia cells in vitro. All of these analogues were investigated for activity versus herpes simplex virus type 1 (HSV-1) and influenza virus (IV-A), as well as the human immunodeficiency virus (HIV). Against HSV-1, only compound 9, the carbocyclic analogue of the lyxofuranoside of guanine, exhibited significant activity, yielding a virus rating (VR) of 2. 1. The corresponding 2,6-diamino compound (10) demonstrated marginal activity, VR = 0.6, against that virus. The test compounds failed to exhibit inhibition of either IV-A or HIV. Additionally, 9 was tested against human cytomegalovirus (HCMV) and was found to display definite activity at concentrations as low as 32.

Original languageEnglish (US)
Pages (from-to)1214-1219
Number of pages6
JournalJournal of medicinal chemistry
Volume33
Issue number4
DOIs
StatePublished - Apr 1990

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