Development of small-molecule P-gp inhibitors of the N-benzyl 1,4-dihydropyridine type: Novel aspects in SAR and bioanalytical evaluation of multidrug resistance (MDR) reversal properties

Christiane Baumert, Marianne Günthel, Sören Krawczyk, Marc Hemmer, Tom Wersig, Andreas Langner, J. Molnár, Hermann Lage, Andreas Hilgeroth

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Novel series of N-benzyl 1,4-dihydropyridines have been prepared by facile syntheses. All relevant substituents of the molecular scaffold have been varied. The resulting compounds were biologically evaluated as P-glycoprotein (P-gp) inhibitors. Substitutions of the N-benzyl residue favour biological activity beside respective 3-ester functions. Most active compounds were further evaluated as multidrug resistance (MDR) modulators to restore the cytotoxic properties of varying daunorubicin applications.

Original languageEnglish
Pages (from-to)166-177
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number1
DOIs
Publication statusPublished - Jan 1 2013

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Daunorubicin
Multiple Drug Resistance
P-Glycoprotein
Bioactivity
Scaffolds
Modulators
Esters
Substitution reactions
Molecules
1,4-dihydropyridine

Keywords

  • Efflux pump inhibition
  • Inhibitor
  • Multidrug resistance (MDR)
  • P-glycoprotein (P-gp)
  • Structure-activity relationships (SAR)

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Development of small-molecule P-gp inhibitors of the N-benzyl 1,4-dihydropyridine type : Novel aspects in SAR and bioanalytical evaluation of multidrug resistance (MDR) reversal properties. / Baumert, Christiane; Günthel, Marianne; Krawczyk, Sören; Hemmer, Marc; Wersig, Tom; Langner, Andreas; Molnár, J.; Lage, Hermann; Hilgeroth, Andreas.

In: Bioorganic and Medicinal Chemistry, Vol. 21, No. 1, 01.01.2013, p. 166-177.

Research output: Contribution to journalArticle

Baumert, Christiane ; Günthel, Marianne ; Krawczyk, Sören ; Hemmer, Marc ; Wersig, Tom ; Langner, Andreas ; Molnár, J. ; Lage, Hermann ; Hilgeroth, Andreas. / Development of small-molecule P-gp inhibitors of the N-benzyl 1,4-dihydropyridine type : Novel aspects in SAR and bioanalytical evaluation of multidrug resistance (MDR) reversal properties. In: Bioorganic and Medicinal Chemistry. 2013 ; Vol. 21, No. 1. pp. 166-177.
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