Imidazo[1,2-b]pyridazines: a potent and selective class of cyclin-dependent kinase inhibitors
Modification of imidazo[1,2-a]pyridine CDK inhibitors lead to identification of less lipophilic imidazo[1,2-b]pyridazine series of CDK inhibitors. Although several equivalent compounds from these two series have similar structure and show similar CDK activity, the SAR of the two series differs signi...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2004-05, Vol.14 (9), p.2249-2252 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | BYTH, Kate F COOPER, Nicola PANNIFER, Andrew ROWSELL, Sian STANWAY, Judith J VALENTINE, Anna L THOMAS, Andrew P CULSHAW, Janet D HEATON, David W OAKES, Sandra E MINSHULL, Claire A NORMAN, Richard A PAUPTIT, Richard A TUCKER, Julie A BREED, Jason |
| description | Modification of imidazo[1,2-a]pyridine CDK inhibitors lead to identification of less lipophilic imidazo[1,2-b]pyridazine series of CDK inhibitors. Although several equivalent compounds from these two series have similar structure and show similar CDK activity, the SAR of the two series differs significantly. Protein inhibitor structure determination has confirmed differences in binding mode and given some understanding of these differences in SAR. Potent and selective imidazo[1,2-b]pyridazine inhibitors of CDK2 have been identified, which show >1 microM plasma levels following a 2mg/kg oral dose to mice. |
| doi_str_mv | 10.1016/j.bmcl.2004.02.008 |
| format | Article |
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Potent and selective imidazo[1,2-b]pyridazine inhibitors of CDK2 have been identified, which show >1 microM plasma levels following a 2mg/kg oral dose to mice.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2004.02.008</identifier><identifier>PMID: 15081018</identifier><language>eng</language><publisher>Oxford: Elsevier</publisher><subject>Animals ; Antineoplastic agents ; Biological and medical sciences ; Cyclin-Dependent Kinases - antagonists & inhibitors ; Enzyme Inhibitors - blood ; Enzyme Inhibitors - chemistry ; Enzyme Inhibitors - pharmacology ; General aspects ; Medical sciences ; Mice ; Models, Molecular ; Pharmacology. 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Although several equivalent compounds from these two series have similar structure and show similar CDK activity, the SAR of the two series differs significantly. Protein inhibitor structure determination has confirmed differences in binding mode and given some understanding of these differences in SAR. Potent and selective imidazo[1,2-b]pyridazine inhibitors of CDK2 have been identified, which show >1 microM plasma levels following a 2mg/kg oral dose to mice.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Cyclin-Dependent Kinases - antagonists & inhibitors</subject><subject>Enzyme Inhibitors - blood</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>General aspects</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Models, Molecular</subject><subject>Pharmacology. 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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2004-05, Vol.14 (9), p.2249-2252 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Antineoplastic agents Biological and medical sciences Cyclin-Dependent Kinases - antagonists & inhibitors Enzyme Inhibitors - blood Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology General aspects Medical sciences Mice Models, Molecular Pharmacology. Drug treatments Pyridazines - blood Pyridazines - chemistry Pyridazines - pharmacology |
| title | Imidazo[1,2-b]pyridazines: a potent and selective class of cyclin-dependent kinase inhibitors |
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