PMID: 9431026Feb 12, 1998Paper

Studies on propafenone-type modulators of multidrug-resistance IV1): synthesis and pharmacological activity of 5-hydroxy and 5-benzyloxy derivatives

Archiv der Pharmazie
P ChibaG Ecker

Abstract

A series of 5-hydroxy and 5-benzyloxy analogs of the antiarrhythmic and multidrug resistance (MDR) modulating drug propafenone was synthesized and the MDR-modulating activity of the compounds was evaluated using a daunomycin efflux assay system. The key step of the synthesis is the selective reduction of the double bond in 1 without cleavage of the benzyl group thus leading to the phenol 3. Alkylation with epichlorohydrine followed by nucleophilic epoxide ring opening gave the benzylated target compounds 5a-d. Subsequent cleavage of the benzyl group gave the 5-hydroxy analogs 6a-d. Structure activity relationship studies showed, that the 5-hydroxy derivates 6a-d fit the log P/log potency correlation line previously established for a series of propafenone analogs. In contrast, all four 5-benzyloxy analogs 5a-d showed almost identical EC50 values, independent of their log P value.

Citations

Jun 13, 2002·Il Farmaco·E TeodoriF Gualtieri
Dec 21, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·A Seelig, E Landwojtowicz
Jan 27, 2005·Bioorganic & Medicinal Chemistry·Silvia DeiElisabetta Teodori

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