title: Evaluation of WO-2014132220, selective PDGFR inhibitors for the treatment of pulmonary arterial hypertension.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is a rare disease currently treated by a range of vasodilator agents and/or endothelin antagonists. Inhibition of platelet derived growth factor receptor (PDGFR) kinases has been suggested to provide an additional therapeutic modality, and clinical studies with the non-selective PDGFR inhibitor imatinib appear to validate this hypothesis. However, side-effects associated with a lack of selectivity suggest clinical utility requires the identification and development of selective PDGFR inhibitors.
  
  
  METHODS
  This application claims derivatives and crystalline forms of two previously claimed PDGFR inhibitors and their use for the treatment of PAH. N-(5-(2-(2,2-dimethylpyrrolidin-1-yl)ethylcarbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide and N-(5-(2-(2,6-cis-dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide have respective IC50 values of 3 and 45 nM in a cellular proliferation assay.
  
  
  CONCLUSIONS
  These two compounds are likely to be selective PDGFR inhibitors. The nature of this filing suggests that Novartis intends to develop at least one of these compounds for the treatment of PAH.
authors.affiliation: Norman Consulting , 18 Pink Lane, Burnham, Bucks, SL1 8JW , UK peter.norman2@btinternet.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Norman
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003460:Crystallization; D015195:Drug Design; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D010330:Patents as Topic; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*
chemical_list: D017479:Receptors, Platelet-Derived Growth Factor
keywords: platelet derived growth factor; platelet derived growth factor receptor kinase inhibitor; pulmonary arterial hypertension; rare disease