Document 1119
 DOCN  M94A1119
 TI    Novel 6-(phenylselenenyl)pyrimidine derivatives as potential anti-AIDS
       agents.
 DT    9412
 AU    Kim DK; Gam J; Kim YW; Kim HT; Cho YB; Kim KH; Shin YO; Sunkyong
       Industries R&D Center, Suwon, Korea.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(2):204 (abstract no. PB0829). Unique
       Identifier : AIDSLINE ICA10/94371456
 AB    OBJECTIVE: To introduce the antiviral activity and ex-vivo
       pharmacodynamics of nonnucleoside reverse transcriptase inhibitors to
       HIV-1 replication in vitro and their properties for clinical
       development. METHODS: The inhibitory activities of these compounds
       against HIV IIIB-induced cytopathogenicity in MT-4 cells were primarily
       evaluated. Several compounds were further assessed for the anti-HIV-1
       activity in MT-2, CEM-SS and PBMC, and for the synergistic effect in
       MT-4 when used in combination with AZT using MTT method and p24 antigen
       ELISA assay. Their antiviral activities to AZT-resistant HIV-1 were
       determined. The pharmacokinetic study was performed in rats. Ex-vivo
       pharmacodynamic study of plasma from rats p.o. administered with 20
       mg/kg of these compounds was undertaken in HIV-1 infected MT-4. RESULTS:
       This series of compounds inhibited HIV-1 replication in MT-4 cells
       displaying IC50s in the range of 0.01-10 nM. Among this series, SKI 1695
       (NSC D665585) and 1703 (NSC D665989) exhibited IC50s ranged from 0.01 to
       10 nM and higher selective index (SI) than 40,000, in various host cell
       lines. And also these two compounds were not cross-resistant to
       AZT-resistant HIV-1 and showed synergistic effect with AZT. In ex-vivo
       study, SKI 1695 completely inhibited the replication of HIV-1 all over
       the sampling time (within 2 hours after administration). DISCUSSION AND
       CONCLUSION: This class of compounds described here has an extremely high
       potential to be developed as a clinically useful anti-AIDS drug.
 DE    Animal  Antiviral Agents/*PHARMACOLOGY  Cells, Cultured  HIV-1/*DRUG
       EFFECTS/GROWTH & DEVELOPMENT  Organoselenium Compounds/*PHARMACOLOGY
       Pyrimidines/*PHARMACOLOGY  Rats  Reverse Transcriptase/*ANTAGONISTS &
       INHIB  Virus Replication/DRUG EFFECTS  MEETING ABSTRACT

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