3RCJ

Rapid preparation of triazolyl substituted NH-heterocyclic kinase inhibitors via one-pot Sonogashira coupling TMS-deprotection CuAAC sequence

Summary for 3RCJ

• Entry DOI: 10.2210/pdb3rcj/pdb
• Related: 3HRC
• Descriptor: 3-phosphoinositide-dependent protein kinase 1, 3-(1-benzyl-1H-1,2,3-triazol-4-yl)-1H-pyrrolo[2,3-b]pyridine (3 entities in total)
• Functional Keywords: agc kinase, serine/threonine-protein kinase, transferase, atp binding, phosphorylation, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: O15530
• Total number of polymer chains: 1
• Total formula weight: 35667.87

Authors

Graedler, U.,Dorsch, D.,Merkul, E.,Klukas, F.,Sirrenberg, C.,Greiner, H.E.,Mueller, T.J.J. (deposition date: 2011-03-31, release date: 2011-06-15, Last modification date: 2024-11-06)

Primary citation

Merkul, E.,Klukas, F.,Dorsch, D.,Gradler, U.,Greiner, H.E.,Muller, T.J.
Rapid preparation of triazolyl substituted NH-heterocyclic kinase inhibitors via one-pot Sonogashira coupling-TMS-deprotection-CuAAC sequence.
Org.Biomol.Chem., 9:5129-5136, 2011

PubMed Abstract: The one-pot, three-component Sonogashira coupling-TMS-deprotection-CuAAC ("click") sequence is the key reaction for the rapid synthesis of triazolyl substituted N-Boc protected NH-heterocycles, such as indole, indazole, 4-, 5-, 6-, and 7-azaindoles, 4,7-diazaindole, 7-deazapurines, pyrrole, pyrazole, and imidazole. Subsequently, the protective group was readily removed to give the corresponding triazolyl derivatives of these tremendously important NH-heterocycles. All compounds have been tested in a broad panel of kinase assays. Several compounds, 8f, 8h, 8k, and 8l, have been shown to inhibit the kinase PDK1, a target with high oncology relevance, and thus they are promising lead structures for the development of more active derivatives. The X-ray structure analysis of compound 8f in complex with PDK1 has revealed the detailed binding mode of the molecule in the kinase.

PubMed: 21625704
DOI: 10.1039/c1ob05586k

Experimental method

X-RAY DIFFRACTION (1.7 Å)