Structure-activity relationships, ligand efficiency, and lipophilic efficiency profiles of benzophenone-type inhibitors of the multidrug transporter P-glycoprotein: Journal of Medicinal Chemistry

I. Jabeen, K. Pleban, U. Rinner, P. Chiba, G.F. Ecker

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

Abstract

The drug efflux pump P-glycoprotein (P-gp) has been shown to promote multidrug resistance (MDR) in tumors as well as to influence ADME properties of drug candidates. Here we synthesized and tested a series of benzophenone derivatives structurally analogous to propafenone-type inhibitors of P-gp. Some of the compounds showed ligand efficiency and lipophilic efficiency (LipE) values in the range of compounds which entered clinical trials as MDR modulators. Interestingly, although lipophilicity plays a dominant role for P-gp inhibitors, all compounds investigated showed LipE values below the threshold for promising drug candidates. Docking studies of selected analogues into a homology model of P-glycoprotein suggest that benzophenones show an interaction pattern similar to that previously identified for propafenone-type inhibitors.

OriginalspracheEnglisch
Seiten (von - bis)3261-3273
Seitenumfang13
FachzeitschriftJ. Med. Chem.
Jahrgang55
Ausgabenummer7
DOIs
PublikationsstatusVeröffentlicht - 27 März 2012
Extern publiziertJa

Fingerprint

Untersuchen Sie die Forschungsthemen von „Structure-activity relationships, ligand efficiency, and lipophilic efficiency profiles of benzophenone-type inhibitors of the multidrug transporter P-glycoprotein: Journal of Medicinal Chemistry“. Zusammen bilden sie einen einzigartigen Fingerprint.

Dieses zitieren