Rational design and synthesis of an orally active indolopyridone as a novel conformationally constrained cannabinoid ligand possessing antiinflammatory properties

  • J Med Chem. 2003 May 22;46(11):2110-6. doi: 10.1021/jm020329q.
Stephen T Wrobleski  1 ,  Ping Chen ,  John Hynes Jr ,  Shuqun Lin ,  Derek J Norris ,  Chennagiri R Pandit ,  Steven Spergel ,  Hong Wu ,  John S Tokarski ,  Xiaorong Chen ,  Kathleen M Gillooly ,  Peter A Kiener ,  Kim W McIntyre ,  Vina Patil-Koota ,  David J Shuster ,  Lori A Turk ,  Guchen Yang ,  Katerina Leftheris
Affiliations
  • 1. Department of Discovery Chemistry, Bristol-Myers Squibb, P.O. Box 4000, Princeton, New Jersey 08543-4000, USA. [email protected]
PMID: 12747783 DOI: 10.1021/jm020329q
Abstract

A series of unique indazoles and pyridoindolones have been rationally designed and synthesized as novel classes of cannabinoid ligands based on a proposed bioactive amide conformation. This has led to the discovery of the novel indolopyridone 3a as a conformationally constrained cannabinoid ligand that displays high affinity for the CB2 receptor (K(i)(CB2) = 1.0 nM) and possesses antiinflammatory properties when administered orally in an in vivo murine inflammation model.

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