title: Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors.
abstract: A series of acylurea analogs derived from pyrrolopyridine and aminopyridine scaffolds were identified as potent inhibitors of Met kinase activity. The SAR at various positions of the two kinase scaffolds was investigated. These studies led to the discovery of compounds 3b and 20b, which demonstrated favorable pharmacokinetic properties in mice and significant antitumor activity in a human gastric carcinoma xenograft model.
authors.affiliation: Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA. zhenwei.cai@bms.com
authors.forename: Zhen-Wei
authors.initials: ZW
authors.lastname: Cai
authors.forename: Donna
authors.initials: D
authors.lastname: Wei
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Schroeder
authors.forename: Lyndon A M
authors.initials: LA
authors.lastname: Cornelius
authors.forename: Kyoung
authors.initials: K
authors.lastname: Kim
authors.forename: Xiao-Tao
authors.initials: XT
authors.lastname: Chen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schmidt
authors.forename: David K
authors.initials: DK
authors.lastname: Williams
authors.forename: John S
authors.initials: JS
authors.lastname: Tokarski
authors.forename: Yongmi
authors.initials: Y
authors.lastname: An
authors.forename: John S
authors.initials: JS
authors.lastname: Sack
authors.forename: Veeraswamy
authors.initials: V
authors.lastname: Manne
authors.forename: Amrita
authors.initials: A
authors.lastname: Kamath
authors.forename: Yueping
authors.initials: Y
authors.lastname: Zhang
authors.forename: Punit
authors.initials: P
authors.lastname: Marathe
authors.forename: John T
authors.initials: JT
authors.lastname: Hunt
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Lombardo
authors.forename: Joseph
authors.initials: J
authors.lastname: Fargnoli
authors.forename: Robert M
authors.initials: RM
authors.lastname: Borzilleri
mesh_terms: D000631:Aminopyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000473:pathology; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000631:Aminopyridines; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D014508:Urea; D019859:Proto-Oncogene Proteins c-met