title: Synthesis and evaluation of a series of 2-substituted-5-thiopropylpiperazine (piperidine)-1,3,4-oxadiazoles derivatives as atypical antipsychotics.
abstract: BACKGROUND
  It is important to develop novel antipsychotics that can effectively treat schizophrenia with minor side-effects. The aim of our work is to develop novel antipsychotics that act on dopamine D(2) and D(3), serotonin 5-HT(1A) and 5-HT(2A) receptors with low affinity for the serotonin 5-HT(2C) and H(1) receptors, which can effectively cure positive symptoms, negative symptoms and cognitive impairment without the weight gain side-effect.
  
  
  RESULTS
  A series of 2-substituted-5-thiopropylpiperazine (piperidine) -1,3,4-oxadiazoles derivatives have been synthesized and the target compounds were evaluated for binding affinities to D(2), 5-HT(1A) and 5-HT(2A) receptors. Preliminary results indicated that compounds 14, 16 and 22 exhibited high affinities to D(2), 5-HT(1A) and 5-HT(2A) receptors among these compounds. Further binding tests showed that compound 22 had high affinity for D(3) receptor, and low affinity for serotonin 5-HT(2C) and H(1) receptors. In addition, compound 22 inhibited apomorphine-induced climbing behavior and MK-801-induced hyperactivity with no extrapyramidal symptoms liability in mice. Moreover, compound 22 exhibited acceptable pharmacokinetic properties.
  
  
  CONCLUSIONS
  Compound 22 showed an atypical antipsychotic activity without liability for extrapyramidal symptoms. We anticipate compound 22 to be useful for developing a novel class of drug for the treatment of schizophrenia.
authors.affiliation: Department of Systems Biology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiangqing
authors.initials: X
authors.lastname: Xu
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Minquan
authors.initials: M
authors.lastname: Yu
authors.forename: Bi-Feng
authors.initials: BF
authors.lastname: Liu
authors.forename: Guisen
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D006948:Hyperkinesis / Q000188:drug therapy; D051379:Mice; D015394:Molecular Structure; D010069:Oxadiazoles / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry*; D011485:Protein Binding; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D010069:Oxadiazoles; D010880:Piperidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D044263:Receptors, Serotonin, 5-HT1