Synthesis of 7-benzyl-5-(piperidin-1-yl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-1-ylamine and its analogs as bombesin receptor subtype-3 agonists

Bioorg Med Chem Lett. 2010 May 1;20(9):2785-9. doi: 10.1016/j.bmcl.2010.03.065. Epub 2010 Mar 17.

Abstract

The original structure of a high-throughput screening hit obtained from an external vendor was revised based on multiple NMR studies. The active compound was re-synthesized via a novel route and its structure and biological activity as a BRS-3 agonist were unambiguously confirmed. Multi-gram quantities of the hit were prepared for pharmacokinetic and efficacy studies. The synthetic strategy allowed for the preparation of multiple analogs for SAR exploration.

MeSH terms

  • Animals
  • Anti-Obesity Agents / chemical synthesis*
  • Anti-Obesity Agents / chemistry
  • Anti-Obesity Agents / pharmacokinetics
  • High-Throughput Screening Assays
  • Humans
  • Naphthyridines / chemical synthesis*
  • Naphthyridines / chemistry
  • Naphthyridines / pharmacokinetics
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacokinetics
  • Rats
  • Receptors, Bombesin / agonists*
  • Receptors, Bombesin / metabolism
  • Structure-Activity Relationship

Substances

  • 7-benzyl-5-(piperidin-1-yl)-6,7,8,9-tetrahydro-3H-pyrazolo(3,4-c)(2,7)-naphthyridin-1-ylamine
  • Anti-Obesity Agents
  • Naphthyridines
  • Pyrazoles
  • Receptors, Bombesin
  • bombesin receptor subtype 3