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 identifi...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2006-05, Vol.16 (10), p.2689-2692
Main Authors: Choi, Ha-Soon, Wang, Zhicheng, Richmond, Wendy, He, Xiaohui, Yang, Kunyong, Jiang, Tao, Karanewsky, Donald, Gu, Xiang-ju, Zhou, Vicki, Liu, Yi, Che, Jianwei, Lee, Christian C., Caldwell, Jeremy, Kanazawa, Takanori, Umemura, Ichiro, Matsuura, Naoko, Ohmori, Osamu, Honda, Toshiyuki, Gray, Nathanael, He, Yun
Format: Article
Language:English
Subjects:
7H-Pyrrolo[2,3-d]pyrimidines
Antineoplastic agents
Biological and medical sciences
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Focal adhesion kinase (FAK)
Focal Adhesion Protein-Tyrosine Kinases - antagonists & inhibitors
General aspects
Kinase inhibitor
Medical sciences
Molecular modeling
Molecular Structure
Pharmacology. Drug treatments
Pyrimidines - chemical synthesis
Pyrimidines - chemistry
Pyrimidines - pharmacology
SAR
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Summary: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 IC50 and represents one of the most potent FAK inhibitors discovered to date.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2006.02.032