New generation dopaminergic agents. 5. Heterocyclic bioisosteres that exploit the 3-OH-N1-phenylpiperazine dopaminergic template

Bioorg Med Chem Lett. 1998 Oct 6;8(19):2675-80. doi: 10.1016/s0960-894x(98)00474-0.

Abstract

The synthesis of several bioisosteric analogs based on the 3-OH-N1-phenylpiperazine dopamine D2 agonist template (i.e., 4) is described. The indolone (5) and 2-CF3-benzimidazole (13) were observed to have excellent affinity for the D2 receptor. Several D4 selective compounds were also identified. Molecular modeling studies and a putative bioactive conformation are discussed.

MeSH terms

  • Animals
  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / pharmacology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / ultrastructure
  • Dopamine Agents / chemical synthesis*
  • Dopamine Agents / pharmacology*
  • Dopamine Agonists / chemical synthesis
  • Dopamine Agonists / pharmacology
  • Indoles / chemical synthesis
  • Indoles / pharmacology
  • Kinetics
  • Piperazines / chemistry*
  • Piperazines / pharmacology*
  • Psychotropic Drugs / chemical synthesis*
  • Psychotropic Drugs / pharmacology*
  • Rats
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3
  • Structure-Activity Relationship
  • Templates, Genetic

Substances

  • Benzimidazoles
  • Dopamine Agents
  • Dopamine Agonists
  • Drd3 protein, rat
  • Indoles
  • Piperazines
  • Psychotropic Drugs
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • phenylpiperazine