Synthesis and structure-activity relationships of 2-(substituted phenyl)-3-[3-(N,N-dimethylamino)propyl]-1,3-thiazolidin-4-ones acting as H-1-histamine antagonists

2-(Substituted-phenyl)-3-[3-(N,N-dimethylamino)propyl]-1,3-thiazolidin-4-on es (1-15) showed dependence of the potency of the H-1-histamine antagonism on the m- and p-substituents suggesting that the aromatic moiety binds the receptor by a strong pi-interaction. Electron-withdrawing substituents decr ease the potency while the electron-donating alkyl substituents, enhancing the aryl HOMO energy, increase the antihistamine activity. The m-substituen ts with the capability to form hydrogen bonds, seems to share an extrainter action with hydrogen accepting or donating groups of the histamine receptor and exhibits very high potency. (C) 1999 Elsevier Science S.A. All rights reserved.