Novel Amino-pyrazole Ureas with Potent In Vitro and In Vivo Antileishmanial Activity

J Med Chem. 2015 Dec 24;58(24):9615-24. doi: 10.1021/acs.jmedchem.5b01456. Epub 2015 Dec 4.

Abstract

Visceral leishmaniasis is a severe parasitic disease that is one of the most neglected tropical diseases. Treatment options are limited, and there is an urgent need for new therapeutic agents. Following an HTS campaign and hit optimization, a novel series of amino-pyrazole ureas has been identified with potent in vitro antileishmanial activity. Furthermore, compound 26 shows high levels of in vivo efficacy (>90%) against Leishmania infantum, thus demonstrating proof of concept for this series.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparasitic Agents / chemistry*
  • Antiparasitic Agents / pharmacokinetics
  • Antiparasitic Agents / pharmacology
  • Cricetinae
  • Female
  • Humans
  • Leishmania donovani / drug effects*
  • Leishmania infantum / drug effects*
  • Leishmaniasis, Visceral / drug therapy
  • Mesocricetus
  • Microsomes / metabolism
  • Pyrazoles / chemistry*
  • Pyrazoles / pharmacokinetics
  • Pyrazoles / pharmacology
  • Structure-Activity Relationship
  • Urea / analogs & derivatives*
  • Urea / chemistry*
  • Urea / pharmacokinetics
  • Urea / pharmacology

Substances

  • 4-(4-fluorophenyl)-N-(3-(pyridin-2-yl)-1H-pyrazol-5-yl)piperazine-1-carboxamide
  • Antiparasitic Agents
  • Pyrazoles
  • Urea