One-pot synthesis of novel tert-butyl-4-substituted phenyl-1H-1,2,3-triazolo piperazine/piperidine carboxylates, potential GPR119 agonists

  • Bioorg Med Chem Lett. 2019 Dec 1;29(23):126707. doi: 10.1016/j.bmcl.2019.126707.
Nagaraju Bashetti  1 ,  J V Shanmukha Kumar  1 ,  Naresh Varma Seelam  1 ,  B Prasanna  1 ,  Akiva Mintz  2 ,  Naresh Damuka  3 ,  Sriram Devanathan  4 ,  Kiran Kumar Solingapuram Sai  5
Affiliations
  • 1. Department of Chemistry, Koneru Lakshmaiah Education Foundation, Andhra Pradesh 522502, India.
  • 2. Department of Radiology, Columbia University Medical Center, New York, NY, USA.
  • 3. Department of Radiology, Wake Forest School of Medicine, Winston Salem, NC, USA.
  • 4. Medical Guidance Systems LLC, St. Louis, MO, USA.
  • 5. Department of Radiology, Wake Forest School of Medicine, Winston Salem, NC, USA. Electronic address: [email protected].
PMID: 31630858 DOI: 10.1016/j.bmcl.2019.126707
Abstract

We have synthesized a new series of 1,2,3-triazolo piperazine and piperidine carboxylate derivatives using a simple and one-pot click chemistry with significantly reduced reaction times (~5 min) and enhanced reaction yields (~95-98%). The fourteen novel compounds thus synthesized were tested for ability to target GPR119, a G-protein coupled target receptor that plays critical role in regulation of type-2 diabetes mellitus. Four analogs (3e, 3g, 5e and 5g) demonstrated similar or better EC50 values over previously reported AR231453 activity towards GPR119.

Keywords
Agonist; Click chemistry; GPR119; PET.