title: Synthesis and structure-activity relationships of 2-(substituted phenyl)-3-[3-(N,N-dimethylamino)propyl]-1,3-thiazolidin-4-ones acting as H1-histamine antagonists.
abstract: 2-(Substituted-phenyl)-3-[3-(N,N-dimethylamino)propyl]-1,3-thiazolidi n-4- ones (1-15) showed dependence of the potency of the H1-histamine antagonism on the m- and p-substituents suggesting that the aromatic moiety binds the receptor by a strong pi-interaction. Electron-withdrawing substituents decrease the potency while the electron-donating alkyl substituents, enhancing the aryl HOMO energy, increase the antihistamine activity. The m-substituents with the capability to form hydrogen bonds, seems to share an extra-interaction with hydrogen accepting or donating groups of the histamine receptor and exhibits very high potency.
authors.affiliation: Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli Federico II, Naples, Italy. diurno@unina.it
authors.forename: M V
authors.initials: MV
authors.lastname: Diurno
authors.forename: O
authors.initials: O
authors.lastname: Mazzoni
authors.forename: G
authors.initials: G
authors.lastname: Correale
authors.forename: I
authors.initials: I
authors.lastname: Gomez Monterrey
authors.forename: A
authors.initials: A
authors.lastname: Calignano
authors.forename: G
authors.initials: G
authors.lastname: La Rana
authors.forename: A
authors.initials: A
authors.lastname: Bolognese
mesh_terms: D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D006634:Histamine H1 Antagonists; D013844:Thiazoles