Synthesis and the 5-HT6 receptor antagonistic effect of 3-arylsulfonylamino-5,6-dihydro-6-substituted pyrazolo[3,4]pyridinones for neuropathic pain treatment

  • Bioorg Med Chem Lett. 2013 Aug 15;23(16):4696-700. doi: 10.1016/j.bmcl.2013.05.100.
Vani Nelamane Devegowda  1 ,  Jin-Ri Hong ,  Sungjin Cho ,  Eun Jeong Lim ,  Hyunah Choo ,  Gyochang Keum ,  Hyewon Rhim ,  Ghilsoo Nam
Affiliations
  • 1. Center for Neuro-Medicine, Brain Science Institute, Korea Institutes of Science and Technology (KIST), Seoul 136-791, Republic of Korea.
PMID: 23820387 DOI: 10.1016/j.bmcl.2013.05.100
Abstract

A novel series of 3-arylsulfonylamino-5,6-dihydro-6-substituted-1H-pyrazolo[3,4-c]pyridine-7-ones was designed and synthesized as 5-HT6 ligands. Among the derivatives synthesized, the lead compound, 12b, having piperidine functionality at the 6-position and (1-naphthyl)sulfonamino at the 3-position of the core structure showed the most potent 5-HT6 inhibitory activity in vitro, good stability without CYP liability, and good neuropathic pain alleviation activity in a rat animal model.

Keywords
5-HT(6) receptor antagonist; Arylsufonylamino-5,6-dihydro-pyrazolo[3,4-c]pyridine-7-one; Neuropathic pain; Synthesis.