title: Tachykinin neurokinin 3 receptor antagonists: a patent review (2005 - 2010).
abstract: BACKGROUND
  The neurokinin 3 (NK(3)) receptor is a GPCR that has been shown to modulate monoaminergic systems within regions of the brain implicated in schizophrenia. Preclinical and Phase II clinical results of osanetant and talnetant in schizophrenic patients have indicated that NK(3) antagonists may provide significant improvement of the positive symptoms and cognitive impairment associated with this disorder. Recent findings have also indicated that neurokinin B (NKB)-NK(3) signaling plays a key role in the hypothalamic regulation of reproduction in humans.
  
  
  METHODS
  This review article discusses the latest medicinal chemistry strategies used to derive novel NK(3) receptor antagonists which have been patented during the period 2005 - 2010.
  
  
  CONCLUSIONS
  Since the report of a beneficial effect of osanetant in schizophrenic patients, major pharmaceutical companies have been involved in this field, leading to a very large number of patent applications disclosed. Nevertheless, only three NK(3) selective antagonists entered into Phase II, but were then terminated for various reasons. Currently, the main challenge to move forward a selective NK(3) antagonist into the clinic would be to define a safety margin between the desired therapeutic effect and the effect on testosterone levels. The involvement of NKB-NK(3) signaling in reproduction in humans may also lead to new exciting indications, such as treatment for sex steroid-sensitive cancers of breast and prostate.
authors.affiliation: F. Hoffmann-La Roche Ltd, Discovery Research CNS, CH-4070 Basel, Switzerland. parichehr.malherbe@roche.com
authors.forename: Pari
authors.initials: P
authors.lastname: Malherbe
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Ballard
authors.forename: Hassen
authors.initials: H
authors.lastname: Ratni
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008969:Molecular Sequence Data; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D010330:Patents as Topic; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D012098:Reproduction; D012559:Schizophrenia / Q000188:drug therapy; D013739:Testosterone / Q000097:blood
chemical_list: D018042:Receptors, Neurokinin-3; D013739:Testosterone; D007986:Luteinizing Hormone