01946nas a2200289   4500000000100000008004100001260001300042653001100055653001200066653004100078653001300119653002300132653001200155653000900167653002500176653003600201653001500237100001600252700001500268700001500283700001800298245009400316300001100410490000700421520121400428022001401642       1985                            d  c1985 Dec10aAmides10aAnimals10aChromatography, High Pressure Liquid10aKinetics10aLeprostatic Agents10aleprosy10aMice10aMycobacterium leprae10aStructure-Activity Relationship10aThioamides1 aShepard C C1 aJenner P J1 aEllard G A1 aLancaster R D00aAn experimental study of the antileprosy activity of a series of thioamides in the mouse.  a587-940 v533 a<p>A series of substituted thioamides have been studied to establish whether their structure-activity pattern against Mycobacterium leprae is similar to that displayed against M. tuberculosis. Antileprosy activity was evaluated in the mouse foot pad using both the kinetic and continuous methods. Ethionamide and prothionamide were found to be the most active compounds and to be of approximately equal potency. Thioisonicotinamide was about five times less active. 2-t-Butyl-thioisonicotinamide, 2-dimethylamino-thioisonicotinamide, and pyrazine carbonic thioamide were inactive at the dosages tested. High-pressure liquid chromatographic methods were devised to study the potential influence of pharmacological factors on their in vivo activity. Fecal measurements suggested that all of the thioamides were well absorbed when fed in the diet. After intravenous administration, all of the thioamides were rapidly eliminated from the mouse. The differences in their elimination rates probably played only a minor role in affecting their relative antileprosy activities. It was concluded that the structural requirements for antileprosy and antituberculosis activity of the thioamides are probably similar.</p>  a0148-916X