Diaryldiamines with dual inhibition of the histamine H(3) receptor and the norepinephrine transporter and the efficacy of 4-(3-(methylamino)-1-phenylpropyl)-6-(2-(pyrrolidin-1-yl)ethoxy)naphthalen-1-ol in pain

J Med Chem. 2010 Nov 11;53(21):7869-73. doi: 10.1021/jm100666w.

Abstract

A series of compounds was designed as dual inhibitors of the H(3) receptor and the norepinephrine transporter. Compound 5 (rNET K(i) = 14 nM; rH(3)R K(i) = 37 nM) was found to be efficacious in a rat model of osteoarthritic pain.

MeSH terms

  • Animals
  • Histamine H3 Antagonists / chemical synthesis*
  • Histamine H3 Antagonists / pharmacokinetics
  • Histamine H3 Antagonists / pharmacology
  • Naphthols / chemical synthesis*
  • Naphthols / pharmacokinetics
  • Naphthols / pharmacology
  • Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors*
  • Osteoarthritis / drug therapy
  • Pain / drug therapy*
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / pharmacokinetics
  • Pyrrolidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship

Substances

  • 4-(3-(methylamino)-1-phenylpropyl)-6-(2-(pyrrolidin-1-yl)ethoxy)naphthalen-1-ol
  • Histamine H3 Antagonists
  • Naphthols
  • Norepinephrine Plasma Membrane Transport Proteins
  • Pyrrolidines