p38 MAP kinase inhibitors. Part 3: SAR on 3, 4-dihydropyrimido [4, 5-d] pyrimidin-2-ones and 3, 4-dihydropyrido [4, 3-d] pyrimidin-2-ones

…, JE Thompson, EA O'Neill, SJ O'Keefe

Index: Natarajan, Swaminathan R.; Wisnoski, David D.; Thompson, James E.; O'Neill, Edward A.; O'Keefe, Stephen J. Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 16 p. 4400 - 4404

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Citation Number: 11

Abstract

p38 inhibitors based on 3, 4-dihydropyrimido [4, 5-d] pyrimidin-2-one and 3, 4-dihydropyrido [4, 3-d] pyrimidin-2-one platforms were synthesized and preliminary SAR explored. Among the pyrimido-pyrimidones the emergence of two sub-types of analogs—C7-amino- pyrimidines such as 24 and C7-amino-piperidines such as 42—characterized with good p38 inhibition and better off-target profiles in terms of ion channel activities was significant. ...