title: Design and synthesis of 7H-pyrrolo[2,3-d]pyrimidines as focal adhesion kinase inhibitors. Part 2.
abstract: A series of 2-amino-9-aryl-7H-pyrrolo[2,3-d]pyrimidines were designed and synthesized as focal adhesion kinase (FAK) inhibitors using molecular modeling in conjunction with a co-crystal structure. Chemistry was developed to introduce functionality onto the 9-aryl ring, which resulted in the identification of potent FAK inhibitors. In particular, compound 32 possessed single-digit nanomolar IC(50) and represents one of the most potent FAK inhibitors discovered to date.
authors.affiliation: Genomics Institute of the Novartis Research Foundation (GNF), 10715 John Jay Hopkins Drive, San Diego, CA 920121, USA.
authors.forename: Ha-Soon
authors.initials: HS
authors.lastname: Choi
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Wendy
authors.initials: W
authors.lastname: Richmond
authors.forename: Xiaohui
authors.initials: X
authors.lastname: He
authors.forename: Kunyong
authors.initials: K
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Donald
authors.initials: D
authors.lastname: Karanewsky
authors.forename: Xiang-ju
authors.initials: XJ
authors.lastname: Gu
authors.forename: Vicki
authors.initials: V
authors.lastname: Zhou
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Jianwei
authors.initials: J
authors.lastname: Che
authors.forename: Christian C
authors.initials: CC
authors.lastname: Lee
authors.forename: Jeremy
authors.initials: J
authors.lastname: Caldwell
authors.forename: Takanori
authors.initials: T
authors.lastname: Kanazawa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Umemura
authors.forename: Naoko
authors.initials: N
authors.lastname: Matsuura
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohmori
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Honda
authors.forename: Nathanael
authors.initials: N
authors.lastname: Gray
authors.forename: Yun
authors.initials: Y
authors.lastname: He
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011743:Pyrimidines; D051416:Focal Adhesion Protein-Tyrosine Kinases