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A series of nine 3-substituted 1-adamantylthioureas was prepared and tested for antiviral activity against influenza A2/Asian/J305 virus in vivo and in vitro. Protective dose 50 values were calculated for three of the compounds. One of these compounds, 7, has antiviral activity which compares favorably with that of amantadine.

The condensation of various halomethyl heterocycles with the potassium salt of the alanine derivative 3, followed by hydrolysis, gave a series of novel 3‐heterocyclic‐2‐methylalanines.

Dedicated to Professor Edgardo Giovannini on his 70th birthday (13.111.80) SummaryReaction of the 1-substituted-3-cyano-isothioureas 6 with hydroxylamine gave mixtures of the 5-amino-3-substituted-amino-1,2,4-oxadiazoles 1 and the isomeric 3-amino-5-substituted-amino-l,2,4-oxadiazoles 8 in which 1 usually predominated. The structural assignment of these products is discussed. In a second method, the 2-hydroxy-1 -methyl-1 -phenyl-guanidine 15 was converted to the corresponding 3-disubstituted-amino-5-trichloromethyl-1,2,4-oxadiazole 16, a precursor to the 5-amino derivatives 17 by nucleophilic displacement of the trichloromethyl group.The structural resemblance of the 3-substituted-amino-5-amino-l,2,4-oxadiazoles 1 to the class of w-adrenergic agonists represented by clonidine 2 and the vasodilating sydnone imide molsidomine 3 led us to prepare selected representatives of this system for cardiovascular evaluation. The early finding that 5-amino-3-phenylamino-l,2,4-oxadiazole (le) elicits in the dog an increase of the cardiac contractility prompted the synthetic studies described below.

The reaction of a variety of 2-bromoacetanilides with amines has been shown to lead to an intramolecular nucleophilic aromatic rearrangement, analogous to the Smiles rearrangement. The reaction is facilitated by activation of the aromatic ring by electron-withdrawing groups in the ortho and para position. With sterically hindered amines no rearrangement is observed. The scope and mechanism of this rearrangement are discussed.The reaction is of synthetic utility for the formation of IP-substituted phenylglycinamides.Aromatic rearrangements which result in the migration of an aromatic system from one heteroatom to another belong to a class of reactions known as the Smiles rearrangement (A-*-B C).2 ABC In most of the early work on the Smiles rearrangement, X was a sulfone group, Y was either an oxygen or nitrogen atom, and the two-carbon bridge was part of an aromatic ring. However, more recent investigations have shown that other heteroatom combinations are possible for X and Y. For example, (1) X can be oxygen, Y nitrogen, and the two-carbon bridge aromatic;3 (2) X can be oxygen, Y nitrogen, and the bridge -NC=0;4 (3) X can be oxygen, Y nitrogen, connected by a three-carbon bridge;5 (4) X can be oxygen, and Y oxygen connected by either an aromatic6 or an aliphatic bridge.7However, no examples of a nitrogen-nitrogen Smiles rearrangement have been reported. The reaction of 2bromoacetanilides with amines represents a novel extension of the Smiles rearrangement in which X and Y are nitrogen atoms connected by a two-carbon aliphatic bridge. Results and DiscussionA typical example of this rearrangement is the reaction of 2-bromo-4'-nitro-VV-methylacetanilide (l)8 with methanolic ammonia, which leads to the rearranged glycinamide2.9The rearrangement is not limited to the use of ammonia for the displacement of bromine, as almost any primary amine causes the formation of rearranged prod-