Pyrrolidin-3-yl-N-methylbenzamides as potent histamine 3 receptor antagonists

Bioorg Med Chem Lett. 2011 Oct 1;21(19):5957-60. doi: 10.1016/j.bmcl.2011.07.061. Epub 2011 Jul 27.

Abstract

On the basis of the previously reported benzimidazole 1,3'-bipyrrolidine benzamides (1), a series of related pyrrolidin-3-yl-N-methylbenzamides were synthesized and evaluated as H(3) receptor antagonists. In particular, compound 32 exhibits potent H(3) receptor binding affinity, improved pharmaceutical properties and a favorable in vivo profile.

MeSH terms

  • Animals
  • Benzamides / chemical synthesis*
  • Benzamides / chemistry
  • Benzamides / pharmacokinetics
  • Benzamides / pharmacology*
  • Brain / metabolism
  • Cognition Disorders / drug therapy
  • Cognition Disorders / physiopathology
  • Diabetes Insipidus / drug therapy
  • Diabetes Insipidus / metabolism
  • Disease Models, Animal
  • Drug Design*
  • Histamine H3 Antagonists / chemical synthesis*
  • Histamine H3 Antagonists / chemistry
  • Histamine H3 Antagonists / pharmacokinetics
  • Histamine H3 Antagonists / pharmacology*
  • Histocompatibility Antigens / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Microsomes, Liver / metabolism
  • Molecular Targeted Therapy
  • Protein Binding
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / chemistry
  • Pyrrolidines / pharmacokinetics
  • Pyrrolidines / pharmacology*
  • Rats
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tripartite Motif Proteins

Substances

  • Benzamides
  • Histamine H3 Antagonists
  • Histocompatibility Antigens
  • Intracellular Signaling Peptides and Proteins
  • Pyrrolidines
  • TRIM10 protein, human
  • Tripartite Motif Proteins

Supplementary concepts

  • Dipsogenic Diabetes Insipidus