Tetrazoles via Multicomponent Reactions

Constantinos G. Neochoritis, Ting Zhao, Alexander Dömling*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

242 Citations (Scopus)
642 Downloads (Pure)

Abstract

Tetrazole derivatives are a prime class of heterocycles, very important to medicinal chemistry and drug design due to not only their bioisosterism to carboxylic acid and amide moieties but also to their metabolic stability and other beneficial physicochemical properties. Although more than 20 FDA-approved drugs contain 1 H- or 2 H-tetrazole substituents, their exact binding mode, structural biology, 3D conformations, and in general their chemical behavior is not fully understood. Importantly, multicomponent reaction (MCR) chemistry offers convergent access to multiple tetrazole scaffolds providing the three important elements of novelty, diversity, and complexity, yet MCR pathways to tetrazoles are far from completely explored. Here, we review the use of multicomponent reactions for the preparation of substituted tetrazole derivatives. We highlight specific applications and general trends holding therein and discuss synthetic approaches and their value by analyzing scope and limitations, and also enlighten their receptor binding mode. Finally, we estimated the prospects of further research in this field.
Original languageEnglish
Pages (from-to)1970-2042
Number of pages73
JournalChemical reviews
Volume119
Issue number3
DOIs
Publication statusPublished - 13-Feb-2019

Keywords

  • article
  • receptor binding
  • substitution reaction
  • tetrazole derivative
  • ONE-POT SYNTHESIS
  • HUMAN DIHYDROFOLATE-REDUCTASE
  • BAYLIS-HILLMAN REACTION
  • AZIDO-UGI REACTION
  • HUISGEN 1,3-DIPOLAR CYCLOADDITION
  • MICROWAVE-ASSISTED SYNTHESIS
  • GROWTH-HORMONE SECRETAGOGUE
  • SOLUTION-PHASE PREPARATION
  • GLYCOGEN-PHOSPHORYLASE-B
  • CLICK CHEMISTRY APPROACH

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