ABSTRACT
From a series of macrocyclic diamides possessing the disulfide linkage, only SRR-SB3, a compound that complexes with zinc, was found to inhibit human immunodeficiency virus type 1 (HIV-1; strain IIIB) replication at a concentration of 1.8 to 6.5 micrograms/ml in MT-4, CEM, and peripheral blood mononuclear cells. SRR-SB3 was toxic to MT-4 cells at a concentration of 15.9 micrograms/ml, resulting in a selectivity index of 9 in these cells. This macrolide was also effective against various other HIV-1 strains, including clinical isolates and HIV-1 strains resistant to protease inhibitors and nucleoside and nonnucleoside reverse transcriptase inhibitors. It was also active against various HIV-2 strains, simian immunodeficiency virus (strain MAC251), and Moloney murine sarcoma virus, but not against viruses other than retroviruses. In addition, the compound was found to inhibit chronic HIV-1 infections in vitro. The compound in combination with other antiviral agents, such as zidovudine, zalcitabine, and stavudine, showed an effect that was between additive and synergistic. Time-of-addition experiments indicated that SRR-SB3 acts at a late stage of the HIV-1 replicative cycle.
Subject(s)
Anti-HIV Agents/pharmacology , Benzamides/pharmacology , Disulfides/pharmacology , HIV-1/drug effects , Virus Replication/drug effects , Animals , Cell Line , DNA, Viral/analysis , Drug Synergism , HIV-1/physiology , Humans , Mice , Moloney murine sarcoma virus/drug effects , Polymerase Chain Reaction , Retroviridae Infections/drug therapy , Retroviridae Infections/virology , Reverse Transcriptase Inhibitors/pharmacology , Sarcoma, Experimental/drug therapy , Sarcoma, Experimental/virology , Tumor Virus Infections/drug therapy , Tumor Virus Infections/virologyABSTRACT
1-Oxo-4-oxa-1,2,3,4-tetrahydrophenanthrene is converted into racemic benz[3,4]-6-oxaestra-1,3,5(10),8-tetraen-17 beta-ol in 45% yield.
Subject(s)
Estrenes/chemical synthesis , Steroids, Heterocyclic/chemical synthesis , Hydrogenation , Molecular Structure , Oxidation-Reduction , StereoisomerismABSTRACT
1,6-Bisthia-4,5,6,7-tetrahydroinden-4-one (I) was converted to racemic A-nor-3,7-bisthiaestra-1,5(10),8,14-tetraen-17(e)-o1 (VI).
Subject(s)
Estrenes , Steroids, Heterocyclic/chemical synthesis , Chemical Phenomena , Chemistry , Magnetic Resonance Spectroscopy , Oxidation-ReductionABSTRACT
2-Phenyl-6-methyl-4-oxo-4,5,6,7-tetrahydrobenzofuran (II) is converted into racemic 2-phenyl-7-methyl-3-oxa-A-nor-14 beta-estra-1,5(10),6,8-tetraen-17 alpha-ol (VIII).
