title: Synthesis and optimization of substituted furo[2,3-d]-pyrimidin-4-amines and 7H-pyrrolo[2,3-d]pyrimidin-4-amines as ACK1 inhibitors.
abstract: Two classes of ACK1 inhibitors, 4,5,6-trisubstituted furo[2,3-d]pyrimidin4-amines and 4,5,6-trisubstituted 7H-pyrrolo[2,3-d]pyrimidin-4-amines, were discovered and evaluated as ACK1 inhibitors. Further structural refinement led to the identification of potent and selective dithiolane inhibitor 37.
authors.affiliation: Department of Medicinal Chemistry, Amgen Inc., 1120 Veterans Blvd., South San Francisco, CA 94080, USA. xjiao@amgen.com
authors.forename: XianYun
authors.initials: X
authors.lastname: Jiao
authors.forename: David J
authors.initials: DJ
authors.lastname: Kopecky
authors.forename: JinSong
authors.initials: J
authors.lastname: Liu
authors.forename: JinQian
authors.initials: J
authors.lastname: Liu
authors.forename: Juan C
authors.initials: JC
authors.lastname: Jaen
authors.forename: Mario G
authors.initials: MG
authors.lastname: Cardozo
authors.forename: Rajiv
authors.initials: R
authors.lastname: Sharma
authors.forename: Nigel
authors.initials: N
authors.lastname: Walker
authors.forename: Holger
authors.initials: H
authors.lastname: Wesche
authors.forename: Shyun
authors.initials: S
authors.lastname: Li
authors.forename: Ellyn
authors.initials: E
authors.lastname: Farrelly
authors.forename: Shou-Hua
authors.initials: SH
authors.lastname: Xiao
authors.forename: Zhulun
authors.initials: Z
authors.lastname: Wang
authors.forename: Frank
authors.initials: F
authors.lastname: Kayser
mesh_terms: D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C577914:7H-pyrrolo(2,3-d)pyrimidin-4-amine; D005663:Furans; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C577915:furo(2,3-d)-pyrimidin-4-amine; D011505:Protein-Tyrosine Kinases; C403262:TNK2 protein, human