Synthesis of a new family of N-aryl lactams active on chemesthesis and taste

A new class of synthetic compds. with chemesthetic activity has been identified. They have been designed ex-novo by structural similarity with known cooling compds. such as menthol, icilin and cyclic ketoenamines, 19 new derivs. have been obtained easily and in high yields by Goldberg arylation or lactam ring closure on the appropriate phenol or benzoic acid deriv. The synthetic procedures are suitable for gram-scale prepn., and the products are stable and easy to purify, 17 new compds. were submitted to preliminary sensory evaluation, and 3 of them showed cooling activity and, in some cases, tingling sensation in the oral cavity. These N-aryl lactams seem to be an interesting class of compds. to be enlarged in order to derive structure-activity relationships.