       Document 0497
 DOCN  M9630497
 TI    Structure-activity relationships in open ansa-chain rifamycin S
       derivatives as inhibitors of HIV-1 reverse transcriptase.
 DT    9603
 AU    Bartolucci C; Cellai L; Marzano M; Segre A; Brufani M; Filocamo L;
       Bianco AD; Guiso M; Brizzi V; Benedetto A; et al; Istituto di
       Strutturistica Chimica G. Giacomello, Roma, Italy.
 SO    Farmaco. 1995 Sep;50(9):587-93. Unique Identifier : AIDSLINE
       MED/96051711
 AB    Three types of open ansa-chain rifamycin S derivatives have been
       prepared: derivatives with the ansa-chain open at C(29) and the original
       dihydrofuranone ring; derivatives with the ansa-chain open at C(29) and
       a furane ring; derivatives with the ansa-chain at open NH-C(15). Only
       derivatives of the first type are weak inhibitors of HIV-1 reverse
       transcriptase (IC50 ca.300 microM) while derivatives of the two other
       types are inactive. It has been hypothesized that the active derivatives
       inhibit the viral enzyme interacting through the groups C(14)H3,
       C(13)H3, and C(1)O at the same site as the well-known inhibitors TIBO
       and Nevirapine. In particular C(13)H3 must be unhindered and in an
       appropriate position out of the plane containing the chromophore-rings.
       The open ansa-chain seems to play the role of a lipophylic substituent.
 DE    Antiviral Agents/*CHEMISTRY/PHARMACOLOGY  HIV-1/DRUG EFFECTS/*ENZYMOLOGY
       Nuclear Magnetic Resonance  Reverse Transcriptase
       Inhibitors/*CHEMISTRY/PHARMACOLOGY  Rifamycins/*CHEMISTRY/*PHARMACOLOGY
       RNA-Directed DNA Polymerase/*DRUG EFFECTS  Structure-Activity
       Relationship  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).

