translation agency

NLM AIDSLINE
Structure-activity relationships in open ansa-chain rifamycin S derivatives as inhibitors of HIV-1 reverse transcriptase.
Bartolucci C; Cellai L; Marzano M; Segre A; Brufani M; Filocamo L;
March 30, 1996
Farmaco. 1995 Sep;50(9):587-93. Unique Identifier : AIDSLINE

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.

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

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