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.
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.
Diurno
M V
MV
Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli Federico II, Naples, Italy. diurno@unina.it
Mazzoni
O
O
Correale
G
G
Gomez Monterrey
I
I
Calignano
A
A
La Rana
G
G
Bolognese
A
A
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*
D006634:Histamine H1 Antagonists; D013844:Thiazoles