title: Evaluation of WO2014075392 and WO2014075393, Merck's first PI3Kδ inhibitor filings.
abstract: BACKGROUND
  There is considerable interest in the development of selective PI3Kδ inhibitors for the treatment of inflammatory diseases and haematological cancers. Merck has no previous filings in this field but licensed Exelixis' programme, including its lead compound XL-499, in December 2011.
  
  
  METHODS
  Both applications claim novel 9-alkyl-6,8-disubstituted purine derivatives as selective δ inhibitors for the treatment of asthma, obstructive airways disease, arthritis and cancer. The two applications differ in the range of exemplified substituents, the first focusing on 8-heteroaryl substituted purines, the second on 8-aminopurine derivatives. Many of the exemplified compounds have IC50 values < 10 nM against PI3Kδ with a number having sub-nanomolar potency.
  
  
  CONCLUSIONS
  The compounds appear to be XL-499 derivatives, some of which are more potent than XL-499. The compounds claimed by Merck are some of the most potent PI3Kδ inhibitors yet described but it is unclear whether a development compound has been identified.
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; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D058534:Class I Phosphatidylinositol 3-Kinases / Q000037:antagonists & inhibitors*; D005371:Filing; D006801:Humans; D010330:Patents as Topic; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011687:Purines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D052999:Quinazolinones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018501:Antirheumatic Agents; D047428:Protein Kinase Inhibitors; D011687:Purines; D052999:Quinazolinones; D058534:Class I Phosphatidylinositol 3-Kinases; C486018:PIK3CD protein, human
keywords: XL-499; asthma; idelalisib; lymphoma; phosphatidylinositol 3-kinase delta inhibitor; rheumatoid arthritis