Molecular Diversity

, Volume 15, Issue 1, pp 3–33 | Cite as

The Gewald multicomponent reaction

  • Yijun Huang
  • Alexander DömlingEmail author


The Gewald reaction of sulfur, cyanoacetic acid derivatives, and oxo-component (G-3CR) yielding highly substituted 2-aminothiophene derivatives has seen diverse applications in combinatorial and medicinal chemistry. Its products are of great use in pharmaceutical industry mainly as small molecular weight inhibitors. We herein review synthetic scope and variations, usage, and structural biology of Gewald products.


Gewald three-component reaction Multicomponent reaction 2-Aminothiophene Sulfur Cyanoacetamide Malonodinitrile Structure–activity relationship Multicomponent reaction MCR 



Gewald three-component reaction


Multicomponent reactions


Protein kinase G


I\({\kappa}\) B kinase β






Polyethylene glycol


Protein tyrosine phosphatase 1B


Ionic liquid


Microwave irradiation


Human glucagon receptor


Tumor necrosis factor-α


c-Jun N-terminal kinase


Kinesin spindle protein


Phosphodiesterase enzyme


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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences and ChemistryUniversity of PittsburghPittsburghUSA

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