دورية أكاديمية
Discovery of 5-pyrrolopyridinyl-2-thiophenecarboxamides as potent AKT kinase inhibitors.
| العنوان: | Discovery of 5-pyrrolopyridinyl-2-thiophenecarboxamides as potent AKT kinase inhibitors. |
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| المؤلفون: | Seefeld MA; Oncology Chemistry, GlaxoSmithKline, Collegeville, PA 19426, USA., Rouse MB, McNulty KC, Sun L, Wang J, Yamashita DS, Luengo JI, Zhang S, Minthorn EA, Concha NO, Heerding DA |
| المصدر: | Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2009 Apr 15; Vol. 19 (8), pp. 2244-8. Date of Electronic Publication: 2009 Feb 27. |
| نوع المنشور: | Comparative Study; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9107377 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1464-3405 (Electronic) Linking ISSN: 0960894X NLM ISO Abbreviation: Bioorg Med Chem Lett Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Elsevier Science Ltd Original Publication: Oxford ; New York : Pergamon Press, c1991- |
| مواضيع طبية MeSH: | Drug Discovery*/methods, Protein Kinase Inhibitors/*chemical synthesis , Proto-Oncogene Proteins c-akt/*antagonists & inhibitors , Pyridines/*chemical synthesis , Pyridines/*pharmacology , Thiophenes/*chemistry, Animals ; Crystallography, X-Ray ; Humans ; Mice ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins c-akt/metabolism ; Thienopyridines ; Thiophenes/chemical synthesis ; Thiophenes/pharmacology |
| مستخلص: | A pyrrolopyridinyl thiophene carboxamide 7 was discovered as a tractable starting point for a lead optimization effort in an AKT kinase inhibition program. SAR studies aided by a co-crystal structure of 7 in AKT2 led to the identification of AKT inhibitors with subnanomolar potency. Representative compounds showed antiproliferative activity as well as inhibition of phosphorylation of the downstream target GSK3beta. |
| المشرفين على المادة: | 0 (5-pyrrolopyridinyl-2-thiophenecarboxamide) 0 (Protein Kinase Inhibitors) 0 (Pyridines) 0 (Thienopyridines) 0 (Thiophenes) EC 2.7.11.1 (AKT2 protein, human) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) |
| تواريخ الأحداث: | Date Created: 20090317 Date Completed: 20090826 Latest Revision: 20120622 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.bmcl.2009.02.094 |
| PMID: | 19285393 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1464-3405 |
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| DOI: | 10.1016/j.bmcl.2009.02.094 |