Cardioselectivity as a function of molecular structure in beta-adrenoceptor blocking agents of the 1-(para-substituted aryloxy)-3-(isopropylamino)propan-2-ol type.

The relationship between molecular structure and cardioselectivity is described in the 1-(para-substituted aryl-oxy)-3-(isoprophylamino)propan-2-ol type of beta-adrenoceptor blocking agents. Cardioselectivity in the aforementioned series requires that the aromatic substitution in the position para to the amino alcohol side chain will have a minimal linear length of 5.0 A. Highest cardioselectivity is obtained when this para substituent is a rigid group coplanar with the aromatic ring. This may result from steric hindrance for binding at the beta2-adrenoceptor subtype which does not occur in the beta1 subtype. Evidence in favor of this suggestion was obtained by the finding that the trans isomer of 1-[4-(1-propenyl)-2-methoxyphenoxy]-3-(isopropylamino)propan-2-ol is cardioselective (beta1/beta2 = 25), whereas the cis isomer is beta2 selective (beta1/beta2 = 0.1).

Inhibition of Moloney leukaemia virus production by N-methylisatin-beta-4':4-diethylthiosemicarbazone.

N-methylisatin-beta-4':4'-diethylthiosemicarbazone (M-IBDET) inhibited the production of Moloney leukaemia virus (MLV). Virus inhibition was related to drug concentrations and time of treatment. The effective antiviral drug concentrations ranged between 3.4 muM and 34 muM. Virus reverse transcriptase activity even at concentrations of 34 muM-M-IBDET was not inhibited. At virus inhibitory concentrations the drug reduced RNA synthesis only very slightly and did not affect protein synthesis at all, although growth and DNA synthesis of host cells were suppressed. The inhibition of cellular DNA synthesis was reversible. Comparison of M-IBDET with actinomycin D, cycloheximide and alpha-amanitin in terms of their inhibitory effect on the release of MLV into the culture medium showed that M-IBDET was comparable to the other antimetabolites. The inhibition of MLV production by M-IBDET was confirmed by various parameters of virus assay. It was concluded from the experimental evidence that M-IBDET specifically inhibits MLV-production.