Synthesis and structure-activity relationships for a series of substituted pyrrolidine NK 1/NK 2 receptor antagonists

…, DL Wenstrup, DW Freund, F Boyer, L Bratton…

Index: Burkholder, Timothy P.; Kudlacz, Elizabeth M.; Maynard, George D.; Liu, Xiao-Gao; Le, Tieu-Binh; Webster, Mark E.; Horgan, Stephen W.; Wenstrup, David L.; Freund, David W.; Boyer, Fred; Bratton, Larry; Gross, Raymond S.; Knippenberg, Robert W.; Logan, Deborah E.; Jones, Bryan K.; Chen, Teng-Man; Geary, Julie L.; Correll, Melinda A.; Poole, J. Chuck; Mandagere, Arun K.; Thompson, Thomas N.; Hwang, Kin-Kai Bioorganic and Medicinal Chemistry Letters, 1997 , vol. 7, # 19 p. 2531 - 2536

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Citation Number: 21

Abstract

We recently described the synthesis and characterization of MDL 105,212, a non peptide tachykinin antagonist with high affinity for NK1 and NK2 receptors. 1 Here we report the synthesis and structure-activity relationships for a series of analogs of MDL 105,212 with regards to: NK1 and NK2 receptor binding affinity, physical-chemical characterization; in vitro absorption potential; in vitro metabolic stability; and efficacy in a capsaicin-challenge ...