Synthesis and activity of four (N,N-dimethylamino)benzamide nonsteroidal anti-inflammatory drugs based on thiazole and thiazoline

Four compounds derived from 2-aminothiazole and 2-amino-2-thiazoline were prepared by coupling the respective bases with the acid chlorides of either 3- or 4-(N,N-dimethylamino)benzoic acid. Products were identified using infrared spectroscopy, 1H NMR spectroscopy and electrospray mass spectroscopy and in two cases by single-crystal X-ray diffraction. Of the four, N-(thiazol-2-yl)-3-(N,N-dimethylamino)-benzamide (1), N-(thiazolin-2-yl)-4-(N,N-dimethylamino)benzamide (2), N-(thiazolin-2-yl)-3-(N,N-dimethylamino) benzamide (3) and N-(thiazolin-2-yl)-4-(N,N-dimethylamino)benzamide (4), the hydrochloride salts of compounds 3 and 4 showed anti-inflammatory activity across a concentration range of 10−2−5 × 10−4 M while 3 (at a concentration of 10−5 M) was found to have no adverse effect on myocardial function. The X-ray crystal structure of 2 and the 1:1 adduct structure of 3 with 3-(N,N-dimethylamino)benzoic acid are reported.