Design, synthesis and structure-activity relationships of a novel class of sulfonylpyridine inhibitors of Interleukin-2 inducible T-cell kinase (ITK)
Starting from benzylpyrimidine 2, molecular modeling and X-ray crystallography were used to design highly potent inhibitors of Interleukin-2 inducible T-cell kinase (ITK). Sulfonylpyridine 4i showed sub-nanomolar affinity against ITK, was selective versus Lck and its activity in the Jurkat cell-base...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2014-12, Vol.24 (24), p.5818-5823 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Trani, Giancarlo Barker, John J Bromidge, Steven M Brookfield, Frederick A Burch, Jason D Chen, Yuan Eigenbrot, Charles Heifetz, Alexander Ismaili, M Hicham A Johnson, Adam Krülle, Thomas M MacKinnon, Colin H Maghames, Rosemary McEwan, Paul A Montalbetti, Christian A G N Ortwine, Daniel F Pérez-Fuertes, Yolanda Vaidya, Darshan G Wang, Xiaolu Zarrin, Ali A Pei, Zhonghua |
| description | Starting from benzylpyrimidine 2, molecular modeling and X-ray crystallography were used to design highly potent inhibitors of Interleukin-2 inducible T-cell kinase (ITK). Sulfonylpyridine 4i showed sub-nanomolar affinity against ITK, was selective versus Lck and its activity in the Jurkat cell-based assay was greatly improved over 2. |
| doi_str_mv | 10.1016/j.bmcl.2014.10.020 |
| format | Article |
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Sulfonylpyridine 4i showed sub-nanomolar affinity against ITK, was selective versus Lck and its activity in the Jurkat cell-based assay was greatly improved over 2.</abstract><cop>England</cop><pmid>25455497</pmid><doi>10.1016/j.bmcl.2014.10.020</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2014-12, Vol.24 (24), p.5818-5823 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Binding Sites Crystallography, X-Ray Drug Design Kinetics Molecular Dynamics Simulation Protein Binding Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - metabolism Protein Structure, Tertiary Protein-Tyrosine Kinases - antagonists & inhibitors Protein-Tyrosine Kinases - metabolism Pyrazoles - chemistry Pyridines - chemical synthesis Pyridines - chemistry Pyridines - metabolism Structure-Activity Relationship Sulfones - chemistry |
| title | Design, synthesis and structure-activity relationships of a novel class of sulfonylpyridine inhibitors of Interleukin-2 inducible T-cell kinase (ITK) |
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