Document 0328
 DOCN  M9610328
 TI    Synthesis and antiviral activity of 8-aza analogs of chiral
       [2-(phosphonomethoxy) propyl]guanines.
 DT    9601
 AU    Franchetti P; Sheikha GA; Cappellacci L; Grifantini M; De Montis A;
       Piras G; Loi AG; La Colla P; Dipartimento di Scienze Chimiche,
       Universita di Camerino, Italy.
 SO    J Med Chem. 1995 Sep 29;38(20):4007-13. Unique Identifier : AIDSLINE
       MED/96005099
 AB    (R)- And (S)-8-aza-9(-)[2-(phosphonomethoxy)propyl]guanine [(R)-and
       (S)-8-aza-PMPG] were synthesized and tested in vitro for anti-human
       immunodeficiency virus (HIV) activity. The synthesis of the above
       compounds and of (R)-9(-)[2-(phosphonomethoxy)propyl]guanine [(R)-PMPG]
       was carried out through the alkylation of 8-azaguanine or guanine with
       (R)- and (S)-2-O(-)[(diisopropylphosphono)methyl]-1-O-(tolylsulfonyl)
       1,2-propanediol followed by deprotection of the phosphonic moiety. A
       different, even more convenient synthesis of (R)-8-aza-PMPG starting
       from 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone and
       (R)(-)[2(-)[(diisopropylphosphono)-methoxy]propyl]amine is also
       reported. Both (R)-8-aza-PMPG and (R)-PMPG demonstrated anti-HIV
       activity in the MTT assay with EC50 values of 12 and 4.5 microM,
       respectively. The corresponding S enantiomers were found to be less
       potent. When evaluated in combination with AZT, ddI, or DABO 603,
       (R)-8-aza-PMPG gave additive, additive, and synergistic anti-HIV-1
       effects, respectively.
 DE    Antiviral Agents/*CHEMICAL SYNTHESIS/PHARMACOLOGY  Aza
       Compounds/*CHEMICAL SYNTHESIS/PHARMACOLOGY  Cell Line  Guanine/*CHEMICAL
       SYNTHESIS/PHARMACOLOGY  Human  HIV/*DRUG EFFECTS  Stereoisomers
       Support, Non-U.S. Gov't  JOURNAL ARTICLE

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