The discovery that 4-[3-ethyl-6-[(3,4-methylenedioxy)phenyl]-3-hexenyl]-3,5-heptanedione (40) exhibited an in vitro inhibitory effect against equine rhinovirus led to a structure--activity study to establish the criteria for optimum activity. Modification of the bridge included removal of the ethyl group and reduction of the double bond. The heptanedione was replaced with hexanedione and pentanedione with a minimal effect. The effect of replacing the heptanedione with beta-keto esters and monoketones was also investigated. Maintaining the hexamethylene bridge and heptanedione, the methylenedioxy group was replaced with various substitutents. In general, most substituents did not adversely affect activity particularly against equine rhinovirus although there was some variation in activity against herpesvirus. Strongly hydrophilic groups significantly reduced activity. Finally, the effect of varying the length of the alkyl bridge was examined in the 4-hydroxyphenyl series, where peak activity was attained with n = 8.

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The preparation of various esters of N-tert-butylarterenol is described. Esterification of the phenolic OH groups has increased bioavailability, prolonged bronchodilation, and reduced tachycardia. The substitution of aromatic esters compared with simple aliphatic esters improved markedly these pharmacological properties. Of a number of esters tested, compound 45 (bitolterol) demonstrated the most favorable pharmacological properties as a bronchodilator. Its long duration of action and significant bronchodilator-cardiovascular separation are briefly described.

The preparation of a variety of 1‐ethyl‐1,4‐dihydro‐4‐oxo‐7‐pyridinyl‐3‐quinolinecarboxylic acids with a range of substituents on the pyridine ring is described. Starting with the appropriately substituted aniline and using the first two steps of the Gould‐Jacobs quinoline synthesis the 7‐pyridinyl‐3‐quinolinecarboxylates can be obtained. Ethylation at the 1‐position and hydrolysis of the ester group gives the desired acid products. These compounds have significant antibacterial activity: 1‐ethyl‐1,4‐dihydro‐4‐oxo‐7‐(4‐pyridinyl)‐3‐quinolinecarboxylic acid is now in clinical study and 7‐(2,6‐dimethyl‐4‐pyridinyl)‐1‐ethyl‐1,4‐dihydro‐4‐oxo‐3‐quinolinecarboxylic acid is under advanced evaluation.

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