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5,6,7,8-Tetrahydropyrido[4,3-d]pyrimidines as novel class of potent and highly selective CaMKII inhibitors
A novel series of 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidines containing substituted phenyl sulfonamide are synthesized and evaluated for their inhibitory activity against CaMKII. Substituents on the phenyl group had significant impact on CaMKII inhibition, in particular, the inhibitory activity of 8...
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| Published in: | Bioorganic & medicinal chemistry letters 2010-11, Vol.20 (22), p.6696-6698 |
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| Main Authors: | , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c417t-75b0126b751aa95ea1b667c236a87d07e144cc415f29658a3b651d0d8ac6c6393 |
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| cites | cdi_FETCH-LOGICAL-c417t-75b0126b751aa95ea1b667c236a87d07e144cc415f29658a3b651d0d8ac6c6393 |
| container_end_page | 6698 |
| container_issue | 22 |
| container_start_page | 6696 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 20 |
| creator | Asano, Shigehiro Komiya, Masafumi Koike, Nobuyuki Koga, Erina Nakatani, Shogo Isobe, Yoshiaki |
| description | A novel series of 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidines containing substituted phenyl sulfonamide are synthesized and evaluated for their inhibitory activity against CaMKII. Substituents on the phenyl group had significant impact on CaMKII inhibition, in particular, the inhibitory activity of 8p was 25-fold higher than that of KN-93, a known CaMKII inhibitor. Michaelis–Menten analysis of a representative compound suggested that the synthesized pyrimidines are calmodulin non-competitive inhibitors. Finally, 8p exhibited more than 100-fold higher selectivity for CaMKII over five types of off-target kinases. |
| doi_str_mv | 10.1016/j.bmcl.2010.09.005 |
| format | article |
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Psychology</subject><subject>Inhibitors</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Pharmacology. 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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2010-11, Vol.20 (22), p.6696-6698 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | ScienceDirect Journals |
| subjects | 5,6,7,8-Tetrahydropyrido[4,3-d]pyrimidines Analytical, structural and metabolic biochemistry Biological and medical sciences Calcium-Calmodulin-Dependent Protein Kinase Type 2 - antagonists & inhibitors Calmodulin-dependent protein kinase II Enzymes and enzyme inhibitors Fundamental and applied biological sciences. Psychology Inhibitors Medical sciences Miscellaneous Pharmacology. Drug treatments Protein Kinase Inhibitors - pharmacology Pyrimidines - pharmacology Transferases |
| title | 5,6,7,8-Tetrahydropyrido[4,3-d]pyrimidines as novel class of potent and highly selective CaMKII inhibitors |
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