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We describe a novel nucleoside analog, 2'-deoxy-3'-thiacytidine (BCH-189), in which the 3' carbon of the ribose ring of 2'-deoxycytidine has been replaced by a sulfur atom. In MT-4 T cells, this compound had significant time- and dose-dependent antiviral activity against five different strains of human immunodeficiency virus type 1 (HIV-1) (mean 50% inhibitory dose, 0.73 microM); known 3'-azido-3'-deoxythymidine (AZT)-resistant HIV-1 variants did not exhibit cross-resistance to it. BCH-189 also suppressed HIV-1 replication in the U937 monocytoid cell line as well as in primary cultures of human peripheral blood mononuclear cells; in these latter systems, suppression was fuller and longer lasting than that induced by AZT. Moreover, BCH-189 was less toxic than AZT in cell culture. BCH-189 may be a promising drug for the treatment of HIV-1-associated disease.

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It was discovered that replacement of the alpha-hydrogens of tyramine and tryptamine by deuterium produces a marked intensification of the blood pressure effects and nictitating membrane contraction normally produced by these amines. The results are interpreted on the basis of kinetic isotope effects at the level of monoamine oxidase and clearly establish the importance of this enzyme in the limitation of responses when tyramine and tryptamine are involved. The observed deuterium isotope effects with alpha,alpha-bisdeuterotyramine (alpha,alpha-D(2)-tyramine) have been reproduced with only one of the optical isomers of monodeuterotyramine. This establishes that the enzyme displays a high degree of optical specificity. The use of l-bisdeuteronorepinephrine revealed that norepinephrine cannot be attacked by the enzyme at the effector cell level.

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