From an atypical wake-promoting agent to potent histamine-3 receptor inverse agonists

Chem Biol Drug Des. 2013 Mar;81(3):433-5. doi: 10.1111/cbdd.12094.

Abstract

Utilizing atypical wake-promoting agent modafinil (inactive in both rH(3) and hH(3) binding assays) as a launching pad, a series of sulfinyl- and sulfone-derived H(3) receptor inverse agonists were developed. Brain-permeable compound 27, a potent member of the series displayed excellent selectivity against related family members (H(1), H(2), and H(4) receptors).

Publication types

  • Letter

MeSH terms

  • Administration, Oral
  • Animals
  • Benzhydryl Compounds / agonists
  • Benzhydryl Compounds / chemistry*
  • Benzhydryl Compounds / pharmacokinetics
  • Central Nervous System Stimulants / agonists
  • Central Nervous System Stimulants / chemistry
  • Central Nervous System Stimulants / pharmacokinetics
  • Drug Inverse Agonism
  • Half-Life
  • Kinetics
  • Modafinil
  • Protein Binding
  • Pyrrolidines / agonists
  • Pyrrolidines / chemistry*
  • Pyrrolidines / pharmacokinetics
  • Rats
  • Receptors, Histamine H3 / chemistry*
  • Receptors, Histamine H3 / metabolism
  • Structure-Activity Relationship
  • Sulfones / agonists
  • Sulfones / chemistry*
  • Sulfones / pharmacokinetics
  • Wakefulness / drug effects

Substances

  • Benzhydryl Compounds
  • Central Nervous System Stimulants
  • Pyrrolidines
  • Receptors, Histamine H3
  • Sulfones
  • Modafinil