… Evaluation of 6-[(6 R)-2-(4-Fluorophenyl)-6-(hydroxymethyl)-4, 5, 6, 7-tetrahydropyrazolo [1, 5-a] pyrimidin-3-yl]-2-(2-methylphenyl) pyridazin-3 (2 H)-one (AS1940477 …

…, H Yamazaki, C Kasahara, H Kubota…

Index: Asano, Toru; Yamazaki, Hitoshi; Kasahara, Chiyoshi; Kubota, Hirokazu; Kontani, Toru; Harayama, Yu; Ohno, Kazuki; Mizuhara, Hidekazu; Ohta, Mitsuaki; Takeuchi., Makoto; Yokomoto, Masaharu; Misumi, Keiji; Kinoshita, Tomohiko Journal of Medicinal Chemistry, 2012 , vol. 55, # 17 p. 7772 - 7785,14 Title/Abstract Full Text Show Details Asano, Toru; Yamazaki, Hitoshi; Kasahara, Chiyoshi; Kubota, Hirokazu; Kontani, Toru; Harayama, Yu; Ohno, Kazuki; Mizuhara, Hidekazu; Yokomoto, Masaharu; Misumi, Keiji; Kinoshita, Tomohiko; Ohta, Mitsuaki; Takeuchi., Makoto Journal of Medicinal Chemistry, 2012 , vol. 55, # 17 p. 7772 - 7785

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Citation Number: 14

Abstract

Several p38 MAPK inhibitors have been shown to effectively block the production of cytokines such as IL-1β, TNFα, and IL-6. Inhibitors of p38 MAP kinase therefore have significant therapeutic potential for the treatment of autoimmune disease. Compound 2a was identified as a potent TNFα production inhibitor in vitro but suffered from poor oral bioavailability. Structural modification of 2a led to the discovery of ...