Design, synthesis and biological evaluation of novel 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as aminopeptidase N/CD13 inhibitors

Bioorg Med Chem. 2011 Oct 15;19(20):6015-25. doi: 10.1016/j.bmc.2011.08.041. Epub 2011 Aug 24.

Abstract

A series of novel 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were designed, synthesized and assayed for their activities against aminopeptidase N (APN/CD13) and MMP-2. The results showed that most compounds exhibited higher inhibitory activities against APN than that of MMP-2. Within this series, compound 12h (IC(50)=6.28 ± 0.11 μM) showed similar inhibitory activities compared with Bestatin (IC(50)=5.55 ± 0.01 μM), and it could be used as novel lead compound for the future APN inhibitors development as anticancer agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • CD13 Antigens / antagonists & inhibitors*
  • CD13 Antigens / chemistry
  • CD13 Antigens / metabolism
  • Drug Design
  • Humans
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Tetrahydroisoquinolines / chemical synthesis*
  • Tetrahydroisoquinolines / chemistry
  • Tetrahydroisoquinolines / pharmacology*

Substances

  • Antineoplastic Agents
  • Protease Inhibitors
  • Tetrahydroisoquinolines
  • 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
  • CD13 Antigens