Synthesis and antitubercular evaluation of novel dibenzo[b,d]furan and 9-methyl-9H-carbazole derived hexahydro-2H-pyrano[3,2-c]quinolines via Povarov reaction

Eur J Med Chem. 2011 Oct;46(10):4827-33. doi: 10.1016/j.ejmech.2011.06.014. Epub 2011 Jul 1.

Abstract

A series of novel hexahydro-2H-pyrano[3,2-c]quinoline analogues derived from dibenzo[b,d]furan and 9-methyl-9H-carbazole has been synthesized in very good yields through SnCl(2)·2H(2)O catalyzed one-pot Povarov reaction (imino-Diels-Alder reaction). The imines generated in situ from dibenzo[b,d]furan-2-carbaldehyde or 9-methyl-9H-carbazole-3-carbaldehyde and aromatic amines, were reacted with 3,4-dihydro-2H-pyran in a diasteroselective manner in acetonitrile at RT. These synthesized isomeric pyranoquinoline analogues have been evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB) by agar dilution method. Among the 23 compounds screened, 5-(dibenzo[b,d]furan-2-yl)-9-fluoro-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline 4f, 5-(dibenzo[b,d]furan-2-yl)-9-fluoro-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline 5f and 9-fluoro-5-(9-methyl-9H-carbazol-3-yl)-3,4,4a,5,6,10b-hexa hydro-2H-pyrano[3,2-c]quinoline 7f (MIC 3.13 μg/mL) were resulted as most active antitubercular agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / chemical synthesis*
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Carbazoles / chemical synthesis
  • Carbazoles / chemistry
  • Carbazoles / pharmacology
  • Humans
  • Imines / chemical synthesis
  • Imines / chemistry
  • Imines / pharmacology
  • Models, Molecular
  • Mycobacterium tuberculosis / drug effects*
  • Pyrans / chemical synthesis
  • Pyrans / chemistry
  • Pyrans / pharmacology
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Structure-Activity Relationship
  • Tuberculosis / drug therapy

Substances

  • Antitubercular Agents
  • Carbazoles
  • Imines
  • Pyrans
  • Quinolines
  • carbazole