2. Academic Validation
  3. Discovery, oral pharmacokinetics and in vivo efficacy of a highly selective 5-HT4 receptor agonist: clinical compound TD-2749

Discovery, oral pharmacokinetics and in vivo efficacy of a highly selective 5-HT4 receptor agonist: clinical compound TD-2749

  • Bioorg Med Chem Lett. 2012 Jul 15;22(14):4849-53. doi: 10.1016/j.bmcl.2012.05.034.
Daniel D Long 1,  Scott R Armstrong,  David T Beattie,  Seok-Ki Choi,  Paul R Fatheree,  Roland A L Gendron,  Adam A Goldblum,  Patrick P Humphrey,  Daniel G Marquess,  Jeng-Pyng Shaw,  Jacqueline A M Smith,  S Derek Turner,  Ross G Vickery
Affiliations

Affiliation

  • 1 Theravance, Inc., 901 Gateway Blvd, South San Francisco, CA 94080, USA. dlong@theravance.com
PMID: 22683222 DOI: 10.1016/j.bmcl.2012.05.034
Abstract

Further application of our multivalent approach to drug discovery directed to 5-HT(4) receptor agonists is described. Optimization of the linker and secondary binding amine in the indazole-tropane primary binding group series, for binding affinity and functional potency at the 5-HT(4) receptor, selectivity over the 5-HT(3) receptor, oral pharmacokinetics, and in vivo efficacy in models of GI motility, resulted in the identification of clinical compound TD-2749.

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