Collect. Czech. Chem. Commun. 1990, 55, 1266-1277

Potential antidepressant and anti-inflammatory agents: 4-(2-Propylthio)acetophenone oximes and 4-(2-propylthio)phenylalkanoic acids

Jiří Jílek, Karel Šindelář, Jaroslava Grimová, Eva Maturová, Jiří Holubek, Emil Svátek, Jiřina Metyšová, Jan Metyš, Marta Hrubantová and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


4-(2-Propylthio)acetophenone oxime (IV) was reacted with 2-aminoethyl chloride and 3-dimethylaminopropyl chloride to give the O-(aminoalkyl)oximes V and VI which are analogues of the antidepressant agent fluvoxamine (I). Kindler-Willgerodt reaction of 4-(2-propylthio)acetophenone (III) gave the thiomorpholide VII which was hydrolyzed to the acid IX. Friedel-Crafts reaction of (2-propylthio)benzene with ethoxalyl chloride afforded ethyl 4-(2-propylthio)benzoylformate (X) which was transformed by reaction with methylmagnesium iodide, by the following hydrolysis and reduction with hydroiodic acid to 2-(4-(2-propylthio)phenyl)propionic acid (XII), a thia isostere of the anti-inflammatory and analgesic agent ibuprofen (II); acid XII was also obtained by reaction of 2-(4-mercaptophenyl)propionic acid (XVII) with 2-bromopropane and by the following hydrolysis. The acids IX and XII were converted to the amides XIII-XV. The fluvoxamine analogue V (V⁄FB-16 650) showed some pharmacological properties of potential antidepressants. The acids IX and XII (V⁄FB-16 603) have comparable anti-inflammatory activity with that of ibuprofen (II); in addition, XII has lower acute toxicity and higher analgetic activity than ibuprofen.