peptidyltransferase target remains to be determined.UV spectra of lb in aqueous solution (pH 7) and ethanol are almost superimposable, which indicates a lack of effective interaction (stacking) between both aromatic portions.21 Similar conclusions can also be drawn from CD spectra showing a greater molecular ellipticity in ethanol than in water. It is, therefore, likely that the conformation of lb is "extended" as found, e.g., in puromycin.22 Further biological testing of lb, along with the synthesis of additional hybrid antibiotics, is the subject of our present investigation.

A series of new nontricyclic antidepressant compounds was synthesized. A representative of this class is compound 6. Five structural parameters were investigated: ring size, cis/trans stereochemistry, amide substitution, aromatic substitution, and amine substitution. The pharmacological tests employed, indicative of antidepressant activity, were yohimbine potentiation test, oxotremorine antagonism test, and apomorphine potentiation test. Structure--activity relationship is discussed.

A series of 8-chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines with substituents at C-4 was prepared and evaluated for antianxiety potential. It was found that substitution at this position generally decreased the activity in this series.

Derivatives of 4-aryl-4-(dimethylamino)cyclohexan-1-ones substituted by m-hydroxy groups were obtained by using as a key reaction the displacement of cyanide from the alpha-aminonitrile of 1,4-cyclohexanedione ketal, with the THP ether of m-hydroxyphenylmagnesium bromide. A number of the products show narcotic antagonist activity. Amino alcohols obtained on reaction of the free ketones with phenethyl Grignard reagents are potent analgetics, though devoid of antagonist activity. Systematic variation of the substituent on nitrogen revealed nonclassical structure-activity relationships; the dimethylamino group gives the most potent antagonist.

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