Synthesis, spasmolytic activity and structure-activity relationship study of a series of polypharmacological thiobenzanilides.
Recently we presented a series of benzanilide derivatives with a selective spasmolytic effect on terminal ileum preparations of the guinea pig. In this report we demonstrate a further development of these compounds. The exchange of the amide oxygen against a sulfur atom resulted in an up to 325 fold increase of the antispasmodic activity of the thiobenzanilide (IC(50) of 0.1 μM) compared to its benzanilide derivative. Considering their mode of action the compounds interacted with several molecular targets, suggesting that we identified a chemical identity able to modulate multiple targets simultaneously. Furthermore, based on this data set, we present a structure-activity relationship study supporting the important role of the sulfur atom.
Department of Medicinal Chemistry, University of Vienna, Althanstraße 14, Vienna, Austria.
Gerda
G
Brunhofer
Christian
C
Studenik
Gerhard F
GF
Ecker
Thomas
T
Erker
D000813:Anilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D015394:Molecular Structure; D009200:Myocardial Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship
D000813:Anilides; D010276:Parasympatholytics; C034595:benzanilide