Synthesis and pharmacological activity of 1,3,6-trisubstituted-4-oxo-1,4- dihydroquinoline-2-carboxylic acids as selective ETA antagonists

Hardik J. Patel, Nicole Olgun, István Lengyel, Sandra Reznik, Ralph A. Stephani

Research output: Contribution to journalArticle

8 Scopus citations


A series of 1,3,6-trisubsituted-4-oxo-1,4-dihyroquinoline-2-carboxylic acid analogs (2a-m) were designed and synthesized and their pharmacological activity determined, with the objective to better understand their SAR as potential ETA selective inhibitors. Most of the compounds displayed significant ETA antagonist activity having IC50 for inhibition of binding of the [125I]ET-1 to ETA receptor <10 nM, with good selectivity for ETA antagonism over ETB receptor. Based on the in vitro results, SAR of this series of compounds requires an alkoxy substituent at the 6-position to be a straight and saturated chain up to three carbons long, since substitution of unsaturated and branched alkyloxy groups results in decrease in ETA antagonist activity. In this series, compound 2c (6-O-n-propyl analog) was found to be most potent (IC 50 = 0.11 nM) with ETB/ETA selectivity of 8303.

Original languageEnglish (US)
Pages (from-to)6840-6844
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number22
Publication statusPublished - Nov 15 2010
Externally publishedYes



  • 4-Oxo-1,4-dihydroquinoline-2-carboxylic acids
  • ETA antagonists
  • ETAR selectivity versus ETBR
  • Endothelin

ASJC Scopus subject areas

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

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