• SyncroPatch 384

    Next level versatility and flexibility
  • SyncroPatch 384

    True HTS and GigaOhm seals
  • SyncroPatch 384

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    Powerful analysis software
  • SyncroPatch 384

    Assay flexibility via high tech
  • SyncroPatch 384

    Heating and cooling of solutions, cells and patch clamp sites

2022- The discovery of (1R, 3R)-1-(3-chloro-5-fluorophenyl)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-6-carbonitrile, a potent and selective agonist of human transient receptor potential cation channel subfamily m member 5 (TRPM5) and evaluation of

 icon sp96 SyncroPatch 384 publication in Bioorganic & Medicinal Chemistry (2022)

Davies M.R., Martinec M., Walls R., Schwarz R., Mirams G.R., Wang K., Steiner G., Surinach A., Flores C., Lave T., Singer T., Polonchuk L.

Bioorganic & Medicinal Chemistry (2022) doi: 10.1016/j.bmc.2022.117084


This publication details the discovery of a series of selective transient receptor potential cation channel subfamily M member 5 (TRPM5) agonists culminating with the identification of the lead compound (1R, 3R)-1-(3-chloro-5-fluorophenyl)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-6-carbonitrile (39). We describe herein our biological rationale for agonism of the target, the examination of the then current literature tool molecules, and finally the process of our discovery starting with a high throughput screening hit through lead development. We also detail the selectivity of the lead compound 39 versus related family members TRPA1, TRPV1, TRPV4, TRPM4 and TRPM8, the drug metabolism and pharmacokinetics (DMPK) profile and in vivo efficacy in a mouse model of gastrointestinal motility.

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