Substituted N-{3-[(1,1-dioxido-1,2-benzothiazol-3-yl)(phenyl)amino]propyl}benzamide analogs as potent Kv1.3 ion channel blockers. Part 2

Bioorg Med Chem Lett. 2010 Dec 1;20(23):6989-92. doi: 10.1016/j.bmcl.2010.09.131. Epub 2010 Oct 23.

Abstract

We report the synthesis and in vitro activity of a series of novel substituted N-{3-[(1,1-dioxido-1,2-benzothiazol-3-yl)(phenyl)amino]propyl}benzamide analogs. These analogs showed potent inhibitory activity against Kv1.3. Several demonstrated similar potency to the known Kv1.3 inhibitor PAP-1 when tested under the IonWorks patch clamp assay conditions. Two compounds 13i and 13rr were advanced further as potential tool compounds for in vivo validation studies.

MeSH terms

  • Amides
  • Animals
  • Benzamides / chemistry*
  • Benzamides / pharmacology*
  • Benzothiazoles / chemistry*
  • Benzothiazoles / pharmacology
  • Cell Line
  • Humans
  • Kv1.3 Potassium Channel / antagonists & inhibitors*
  • Pancreatitis-Associated Proteins
  • Patch-Clamp Techniques
  • Rats
  • Structure-Activity Relationship

Substances

  • Amides
  • Benzamides
  • Benzothiazoles
  • Kv1.3 Potassium Channel
  • Pancreatitis-Associated Proteins
  • REG3A protein, human