Discovery of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines as potent inhibitors of the insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase

Samarjit Patnaik; Kirk L Stevens; Roseanne Gerding; Felix Deanda; J Brad Shotwell; Jun Tang; Toshihiro Hamajima; Hiroko Nakamura; M Anthony Leesnitzer; Anne M Hassell; Lisa M Shewchuck; Rakesh Kumar; Huangshu Lei; Stanley D Chamberlain

doi:10.1016/j.bmcl.2008.12.110

Discovery of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines as potent inhibitors of the insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase

Bioorg Med Chem Lett. 2009 Jun 1;19(11):3136-40. doi: 10.1016/j.bmcl.2008.12.110. Epub 2009 Jan 6.

Authors

Samarjit Patnaik¹, Kirk L Stevens, Roseanne Gerding, Felix Deanda, J Brad Shotwell, Jun Tang, Toshihiro Hamajima, Hiroko Nakamura, M Anthony Leesnitzer, Anne M Hassell, Lisa M Shewchuck, Rakesh Kumar, Huangshu Lei, Stanley D Chamberlain

Affiliation

¹ GlaxoSmithKline, Oncology R&D, NC 27709, USA. [email protected]

PMID: 19394223
DOI: 10.1016/j.bmcl.2008.12.110

Abstract

Exploration of the SAR around a series of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines led to the discovery of novel pyrrolopyridine inhibitors of the IGF-1R tyrosine kinase. Several compounds demonstrated nanomolar potency in enzyme and cellular mechanistic assays.

MeSH terms

Drug Design
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology
Pyridines / chemical synthesis
Pyridines / chemistry*
Pyridines / pharmacology
Pyrroles / chemical synthesis
Pyrroles / chemistry*
Pyrroles / pharmacology
Receptor, IGF Type 1 / antagonists & inhibitors*
Receptor, IGF Type 1 / metabolism
Structure-Activity Relationship

Substances

Protein Kinase Inhibitors
Pyridines
Pyrroles
Receptor, IGF Type 1