title: New pyrazolo[1,5a]pyrimidines as orally active inhibitors of Lck.
abstract: A novel series of pyrazolo[1,5a]pyrimidines was optimized to target lymphocyte-specific kinase (Lck). An efficient synthetic route was developed and SAR studies toward activity and selectivity are described, leading to Lck inhibitors with enzymatic, cellular and in vivo potency.
authors.affiliation: Novartis Institute of Biomedical Research, Forum 1, Novartis Campus, Basel, Switzerland. nina.gommermann@novartis.com
authors.forename: Nina
authors.initials: N
authors.lastname: Gommermann
authors.forename: Peter
authors.initials: P
authors.lastname: Buehlmayer
authors.forename: Anette
authors.initials: A
authors.lastname: von Matt
authors.forename: Werner
authors.initials: W
authors.lastname: Breitenstein
authors.forename: Keiichi
authors.initials: K
authors.lastname: Masuya
authors.forename: Bernard
authors.initials: B
authors.lastname: Pirard
authors.forename: Pascal
authors.initials: P
authors.lastname: Furet
authors.forename: Sandra W
authors.initials: SW
authors.lastname: Cowan-Jacob
authors.forename: Gisbert
authors.initials: G
authors.lastname: Weckbecker
mesh_terms: D000284:Administration, Oral; D000818:Animals; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors*; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D007376:Interleukin-2; D011743:Pyrimidines; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)