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, 1 H 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.