Novel structure-activity relationships and selectivity profiling of cage dimeric 1,4-dihydropyridines as multidrug resistance (MDR) modulators

作者：Coburger Claudius; Wollmann Joerg; Krug Martin; Baumert Christiane; Seifert Marianne; Molnar Josef; Lage Hermann; Hilgeroth Andreas^*

来源：Bioorganic & Medicinal Chemistry, 2010, 18(14): 4983-4990.

DOI：10.1016/j.bmc.2010.06.004

• Structure-activity relationships (SAR)
• Multidrug resistance (MDR)
• P-Glycoprotein (P-gp)
• Multidrug resistance associated protein (MRP)
• Breast cancer resistant protein (BCRP)
• Selectivity

Synthesized series of cage dimeric 1,4-dihydropyridines have been systematically evaluated as MDR modulators in in vitro assays to investigate structure-dependent selectivity properties of inhibiting most cancer-relevant efflux pump proteins. Structure-activity relationships of each P-glycoprotein (P-gp) and multidrug resistance associated protein (MRP) 1 and MRP2 inhibition are discussed and prove to be mainly determined by certain aromatic substitution patterns. The characterization of breast cancer resistance protein (BCRP) inhibition results in the discovery of benzyloxy substituted derivatives as selective P-gp inhibitors.

• 出版日期2010-7-15