Tetrahydroindolizinone NK1 antagonists

Jianming Bao, Huagang Lu, Gregori J. Morriello, Emma J. Carlson, Alan Wheeldon, Gary G. Chicchi, Marc M. Kurtz, Kwei Lan C. Tsao, Song Zheng, Xinchun Tong, Sander G. Mills, Robert J. DeVita

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


A new class of potent NK1 receptor antagonists with a tetrahydroindolizinone core has been identified. This series of compounds demonstrated improved functional activities as compared to previously identified 5,5-fused pyrrolidine lead structures. SAR at the 7-position of the tetrahydroindolizinone core is discussed in detail. A number of compounds displayed high NK1 receptor occupancy at both 1 h and 24 h in a gerbil foot tapping model. Compound 40 has high NK1 binding affinity, good selectivity for other NK receptors and promising in vivo properties. It also has clean P450 inhibition and hPXR induction profiles.

Original languageEnglish
Pages (from-to)2354-2358
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number7
StatePublished - 1 Apr 2010
Externally publishedYes


  • Antagonists
  • Gerbil foot tapping
  • IP1
  • NK1
  • Tetrahydroindolizinone


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