Synthesis and contractile activity of substituted 1,2,3,4-tetrahydroisoquinolines

Molecules. 2011 Aug 16;16(8):7019-42. doi: 10.3390/molecules16087019.

Abstract

A series of different 1-monosubstituted and 1,1-disubstituted 1,2,3,4-tetrahydro-isoquinolines was synthesized in high yields from different ketoamides. We have developed a convenient method for the synthesis of disubstituted derivatives by interaction of ketoamides with organomagnesium compounds, followed by cyclization in the presence of catalytic amounts of p-toluenesulfonic acid (PTSA). A number of substituents at the C-1 in the isoquinoline skeleton were introduced varying either carboxylic acid or organomagnesium compound. Some of the obtained 1,1-dialkyl-1,2,3,4-tetrahydro-isoquinolines possess contractile activity against guinea pig's gastric smooth muscle preparations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Acetylcholine / pharmacology
  • Amides / chemistry
  • Animals
  • Area Under Curve
  • Benzenesulfonates / chemistry
  • Catalysis
  • Chemistry, Pharmaceutical / methods*
  • Cholinergic Agonists* / chemical synthesis
  • Cholinergic Agonists* / pharmacology
  • Cyclization
  • Guinea Pigs
  • Magnetic Resonance Spectroscopy
  • Male
  • Muscle Contraction / drug effects*
  • Muscle Contraction / physiology
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiology
  • Organ Culture Techniques
  • Organometallic Compounds* / chemical synthesis
  • Organometallic Compounds* / pharmacology
  • Receptors, Cholinergic / metabolism*
  • Structure-Activity Relationship
  • Tetrahydroisoquinolines* / chemical synthesis
  • Tetrahydroisoquinolines* / pharmacology

Substances

  • Amides
  • Benzenesulfonates
  • Cholinergic Agonists
  • Organometallic Compounds
  • Receptors, Cholinergic
  • Tetrahydroisoquinolines
  • Acetylcholine
  • 4-toluenesulfonic acid