Click chemistry inspired one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles and their Src kinase inhibitory activity

Bioorg Med Chem Lett. 2011 Jan 1;21(1):449-52. doi: 10.1016/j.bmcl.2010.10.121. Epub 2010 Oct 30.

Abstract

Two classes of 1,4-disubstituted 1,2,3-triazoles were synthesized using one-pot reaction of α-tosyloxy ketones/α-halo ketones, sodium azide, and terminal alkynes in the presence of aq PEG (1:1, v/v) using the click chemistry approach and evaluated for Src kinase inhibitory activity. Structure-activity relationship analysis demonstrated that insertion of C(6)H(5)- and 4-CH(3)C(6)H(4)- at position 4 for both classes and less bulkier aromatic group at position 1 in class 1 contribute critically to the modest Src inhibition activity (IC(50) = 32-43 μM) of 1,4-disubstituted 1,2,3-triazoles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / chemistry
  • Binding Sites
  • Click Chemistry
  • Computer Simulation
  • Morpholines / chemistry
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Sodium Azide / chemistry
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*
  • Triazoles / pharmacology
  • src-Family Kinases / antagonists & inhibitors*
  • src-Family Kinases / metabolism

Substances

  • Alkynes
  • Morpholines
  • Protein Kinase Inhibitors
  • Triazoles
  • poly (3-morpholinopropyl) aspartamide
  • Aspartic Acid
  • Sodium Azide
  • src-Family Kinases