Antibacterial activities of Groebke-Blackburn-Bienaymé-derived imidazo[1,2-a]pyridin-3-amines

Nikunj M. Shukla, Deepak B. Salunke, Euna Yoo, Cole A. Mutz, Rajalakshmi Balakrishna, Sunil A. David

Research output: Contribution to journalArticlepeer-review

126 Scopus citations


We sought to explore the imidazo[1,2-a]pyridin-3-amines for TLR7 (or 8)-modulatory activities. This chemotype, readily accessed via the Groebke-Blackburn-Bienaymé multi-component reaction, resulted in compounds that were TLR7/8-inactive, but exhibited bacteriostatic activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). To investigate the mechanism of antibacterial activity of this new chemotype, a resistant strain of S. aureus was generated by serially passaging the organism in escalating doses of the most active analogue. A comparison of minimum inhibitory concentrations (MICs) of known bacteriostatic agents in wild-type and resistant strains indicates a novel mechanism of action. Structure-activity relationship studies have led to the identification of positions on the scaffold for additional structural modifications that should allow for the introduction of probes designed to examine cognate binding partners and molecular targets, while not significantly compromising antibacterial potency.

Original languageEnglish (US)
Pages (from-to)5850-5863
Number of pages14
JournalBioorganic and Medicinal Chemistry
Issue number19
StatePublished - Oct 1 2012

Bibliographical note

Funding Information:
This work was supported by NIH/NIAID contract HHSN272200900033C.


  • Antibacterials
  • Antibiotics
  • Bacteriostatic
  • Groebke reaction
  • Imidazopyridines
  • MRSA
  • Multicomponent reaction


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