Design and synthesis of 7H-pyrrolo[2,3-d]pyrimidines as focal adhesion kinase inhibitors. Part 2.
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.
Choi
Ha-Soon
HS
Genomics Institute of the Novartis Research Foundation (GNF), 10715 John Jay Hopkins Drive, San Diego, CA 920121, USA.
Wang
Zhicheng
Z
Richmond
Wendy
W
He
Xiaohui
X
Yang
Kunyong
K
Jiang
Tao
T
Karanewsky
Donald
D
Gu
Xiang-ju
XJ
Zhou
Vicki
V
Liu
Yi
Y
Che
Jianwei
J
Lee
Christian C
CC
Caldwell
Jeremy
J
Kanazawa
Takanori
T
Umemura
Ichiro
I
Matsuura
Naoko
N
Ohmori
Osamu
O
Honda
Toshiyuki
T
Gray
Nathanael
N
He
Yun
Y
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
D004791:Enzyme Inhibitors; D011743:Pyrimidines; D051416:Focal Adhesion Protein-Tyrosine Kinases