Syntheses of novel 2,3-diaryl-substituted 5-cyano-4-azaindoles exhibiting c-Met inhibition activity

Hannes Koolman; Timo Heinrich; Henning Böttcher; Wilfried Rautenberg; Michael Reggelin

doi:10.1016/j.bmcl.2009.02.069

Syntheses of novel 2,3-diaryl-substituted 5-cyano-4-azaindoles exhibiting c-Met inhibition activity

Bioorg Med Chem Lett. 2009 Apr 1;19(7):1879-82. doi: 10.1016/j.bmcl.2009.02.069. Epub 2009 Feb 21.

Authors

Hannes Koolman¹, Timo Heinrich, Henning Böttcher, Wilfried Rautenberg, Michael Reggelin

Affiliation

¹ Clemens-Schöpf Institute of Organic Chemistry and Biochemistry, Technical University of Darmstadt, Petersenstrasse 22, 64287 Darmstadt, Germany. hannes.koolman@merck.de

PMID: 19269177
DOI: 10.1016/j.bmcl.2009.02.069

Abstract

Herein we report the syntheses of 2,3-diaryl-substituted pyrrolo[3,2-b]pyridine-5-carbonitriles via a one-pot 5-endo-dig-cyclization/protection reaction followed by palladium catalyzed arylation. In addition, a complementary synthesis route employing Larock methodology is applied to efficiently explore further aryl moieties in the 2-position. The novel compounds' expedient c-Met receptor tyrosine kinase inhibition activity is discussed.

MeSH terms

Catalysis
Indoles / chemical synthesis*
Indoles / chemistry
Indoles / pharmacology
Inhibitory Concentration 50
Palladium / chemistry
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins c-met / antagonists & inhibitors*
Proto-Oncogene Proteins c-met / metabolism

Substances

Indoles
Protein Kinase Inhibitors
Palladium
Proto-Oncogene Proteins c-met