دورية أكاديمية
N-4-Pyrimidinyl-1H-indazol-4-amine inhibitors of Lck: indazoles as phenol isosteres with improved pharmacokinetics.
| العنوان: | N-4-Pyrimidinyl-1H-indazol-4-amine inhibitors of Lck: indazoles as phenol isosteres with improved pharmacokinetics. |
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| المؤلفون: | Bamborough P; GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. Paul.A.Bamborough@gsk.com, Angell RM, Bhamra I, Brown D, Bull J, Christopher JA, Cooper AW, Fazal LH, Giordano I, Hind L, Patel VK, Ranshaw LE, Sims MJ, Skone PA, Smith KJ, Vickerstaff E, Washington M |
| المصدر: | Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2007 Aug 01; Vol. 17 (15), pp. 4363-8. Date of Electronic Publication: 2007 Apr 13. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9107377 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0960-894X (Print) 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: | Enzyme Inhibitors/*pharmacology , Indazoles/*pharmacology , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/*antagonists & inhibitors, Enzyme Inhibitors/pharmacokinetics ; Indazoles/pharmacokinetics ; Models, Molecular |
| مستخلص: | 2,4-Dianilino pyrimidines are well-known inhibitors of tyrosine kinases including lymphocyte specific kinase (Lck). Structure-activity relationships at the 4-position are discussed and rationalised. Examples bearing a 2-methyl-5-hydroxyaniline substituent at the 4-position were especially potent but showed poor oral pharmacokinetics. Replacement of this substituent by 4-amino(5-methyl-1H-indazole) yielded compounds with comparable enzyme potency and improved pharmacokinetic properties. |
| المشرفين على المادة: | 0 (Enzyme Inhibitors) 0 (Indazoles) EC 2.7.10.2 (Lymphocyte Specific Protein Tyrosine Kinase p56(lck)) |
| تواريخ الأحداث: | Date Created: 20070630 Date Completed: 20071001 Latest Revision: 20091119 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.bmcl.2007.04.029 |
| PMID: | 17600705 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 0960-894X |
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| DOI: | 10.1016/j.bmcl.2007.04.029 |