دورية أكاديمية
(1-(4-(Naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine: a wingless beta-catenin agonist that increases bone formation rate.
| العنوان: | (1-(4-(Naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine: a wingless beta-catenin agonist that increases bone formation rate. |
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| المؤلفون: | Pelletier JC; Chemical Sciences, Drug Safety & Metabolism, Wyeth Research, 500 Arcola Road, Collegeville, Pennsylvania 19426, USA. Pelletj@wyeth.com, Lundquist JT 4th, Gilbert AM, Alon N, Bex FJ, Bhat BM, Bursavich MG, Coleburn VE, Felix LA, Green DM, Green P, Hauze DB, Kharode YP, Lam HS, Lockhead SR, Magolda RL, Matteo JJ, Mehlmann JF, Milligan C, Murrills RJ, Pirrello J, Selim S, Sharp MC, Unwalla RJ, Vera MD, Wrobel JE, Yaworsky P, Bodine PV |
| المصدر: | Journal of medicinal chemistry [J Med Chem] 2009 Nov 26; Vol. 52 (22), pp. 6962-5. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Chemical Society Original Publication: [Easton, Pa.] : American Chemical Society, [c1963- |
| مواضيع طبية MeSH: | Osteogenesis/*drug effects , Piperidines/*pharmacology , Pyrimidines/*pharmacology , Wnt Proteins/*agonists , beta Catenin/*agonists, Animals ; Catalytic Domain ; Cell Line, Tumor ; Glycogen Synthase Kinase 3/antagonists & inhibitors ; Glycogen Synthase Kinase 3/chemistry ; Glycogen Synthase Kinase 3 beta ; Humans ; Mice ; Models, Molecular ; Piperidines/administration & dosage ; Piperidines/pharmacokinetics ; Pyrimidines/administration & dosage ; Pyrimidines/pharmacokinetics ; Rats ; Signal Transduction/drug effects ; Wnt Proteins/metabolism ; beta Catenin/metabolism |
| مستخلص: | A high-throughput screening campaign to discover small molecule leads for the treatment of bone disorders concluded with the discovery of a compound with a 2-aminopyrimidine template that targeted the Wnt beta-catenin cellular messaging system. Hit-to-lead in vitro optimization for target activity and molecular properties led to the discovery of (1-(4-(naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine (5, WAY-262611). Compound 5 has excellent pharmacokinetic properties and showed a dose dependent increase in the trabecular bone formation rate in ovariectomized rats following oral administration. |
| المشرفين على المادة: | 0 (Piperidines) 0 (Pyrimidines) 0 (WAY-262611) 0 (Wnt Proteins) 0 (beta Catenin) EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) EC 2.7.11.26 (Glycogen Synthase Kinase 3) |
| تواريخ الأحداث: | Date Created: 20091028 Date Completed: 20091221 Latest Revision: 20220126 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1021/jm9014197 |
| PMID: | 19856966 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1520-4804 |
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| DOI: | 10.1021/jm9014197 |