       Document 0414
 DOCN  M9650414
 TI    2-Sulfonyl-4-chloroanilino moiety: a potent pharmacophore for the
       anti-human immunodeficiency virus type 1 activity of pyrrolyl aryl
       sulfones.
 DT    9605
 AU    Artico M; Silvestri R; Massa S; Loi AG; Corrias S; Piras G; La Colla P;
       Dipartimento di Studi Farmaceutici, Universita di Roma, Italy.
 SO    J Med Chem. 1996 Jan 19;39(2):522-30. Unique Identifier : AIDSLINE
       MED/96145187
 AB    The synthesis and the evaluation of cytotoxicity and anti-HIV-1 activity
       of new aryl pyrrolyl (8) and aryl indolyl (9) sulfones are reported.
       Preparation of above sulfones was achieved by reacting arylsulfonyl
       chlorides with substituted pyrroles and indoles or by condensing
       sulfonamides with 2,5-dimethoxytetrahydrofuran in glacial acetic acid
       according to the Clauson-Kaas method. Chemical requisites relevant to
       the anti-HIV-1 activity of these compounds are both a
       2-sulfonyl-4-chloroanilino moiety and an alkoxycarbonyl group at
       position 2 of the pyrrole ring. The best activity and selectivity were
       obtained with ethoxycarbonyl and isopropoxycarbonyl substituents.
       Substitutions at the amino group of the pharmacophore moiety led to
       inactive products (alkylation) or weakened (acylation) anti-HIV-1
       activity. Among test derivatives, 16 compounds showed EC50 values
       ranging between 10 and 1 microM, and five (8b',d',f',h'j') showed EC50S
       in the sub-micromolar range. The compounds were active against HIV-1,
       both wild type and AZT-resistant strains, but not against HIV-2.
       Moreover, in enzyme assays they potently inhibited the HIV-1 recombinant
       reverse transcriptase, were 10 times less active against enzymes from
       nevirapine- and TIBO-resistant strains, and were totally inactive
       against the HIV-2 recombinant enzyme. Interestingly, some compounds
       (8r'-y') were inactive against the recombinant reverse transcriptase
       while being active in tissue culture.
 DE    Antiviral Agents/CHEMISTRY/*PHARMACOLOGY  Cell Line  Cytopathogenic
       Effect, Viral/DRUG EFFECTS  HIV-1/*DRUG EFFECTS/PATHOGENICITY
       HIV-2/*DRUG EFFECTS/PATHOGENICITY  Nuclear Magnetic Resonance  Sulfinic
       Acids/*CHEMISTRY  Sulfones/CHEMISTRY/*PHARMACOLOGY  Support, Non-U.S.
       Gov't  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

