Novel type of plasmin inhibitors: providing insight into P4 moiety and alternative scaffold to pyrrolopyrimidine

Bioorg Med Chem. 2015 Jul 1;23(13):3696-704. doi: 10.1016/j.bmc.2015.04.013. Epub 2015 Apr 10.

Abstract

Here we report a series of plasmin inhibitors which were originally derived from the parent structure of 1 and 2. Our efforts focused on the optimization of the P4 moiety of 2 and on the quest of alternative scaffold to pyrrolopyrimidine in the parent compounds. The results of the former gave us pivotal information on the further optimization of the P4 moiety in plasmin inhibitors and those of the latter revealed that appropriate moieties extending from the benzimidazole scaffold engaged with S4 pocket in the active site of plasmin.

Keywords: Benzimidazole; P4 moiety; Plasmin inhibitors; Pyrrolopyrimidine; Scaffold; Structure–activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifibrinolytic Agents / chemical synthesis
  • Antifibrinolytic Agents / chemistry*
  • Benzimidazoles / chemistry
  • Catalytic Domain
  • Fibrinolysin / antagonists & inhibitors*
  • Fibrinolysin / chemistry
  • Fibrinolytic Agents / chemistry*
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry*
  • Structure-Activity Relationship

Substances

  • Antifibrinolytic Agents
  • Benzimidazoles
  • Fibrinolytic Agents
  • Pyrimidines
  • Pyrroles
  • pyrrolopyrimidine
  • Fibrinolysin