Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38&#945; mitogen-activated protein kinase.

Goldstein, David M; Soth, Michael; Gabriel, Tobias; Dewdney, Nolan; Kuglstatter, Andreas; Arzeno, Humberto; Chen, Jeffrey; Bingenheimer, William; Dalrymple, Stacie A; Dunn, James; Farrell, Robert; Frauchiger, Sandra; La Fargue, JoAnn; Ghate, Manjiri; Graves, Bradford; Hill, Ronald J; Li, Fujun; Litman, Renee; Loe, Brad; McIntosh, Joel; McWeeney, Daniel; Papp, Eva; Park, Jaehyeon; Reese, Harlan F; Roberts, Richard T; Rotstein, David; San Pablo, Bong; Sarma, Keshab; Stahl, Martin; Sung, Man-Ling; Suttman, Rebecca T; Sjogren, Eric B; Tan, Yunchou; Trejo, Alejandra; Welch, Mary; Weller, Paul; Wong, Brian R; Zecic, Hasim

Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38α mitogen-activated protein kinase.

Goldstein, David M; Soth, Michael; Gabriel, Tobias; Dewdney, Nolan; Kuglstatter, Andreas; Arzeno, Humberto; Chen, Jeffrey; Bingenheimer, William; Dalrymple, Stacie A; Dunn, James; Farrell, Robert; Frauchiger, Sandra; La Fargue, JoAnn; Ghate, Manjiri; Graves, Bradford; Hill, Ronald J; Li, Fujun; Litman, Renee; Loe, Brad; McIntosh, Joel; McWeeney, Daniel; Papp, Eva; Park, Jaehyeon; Reese, Harlan F; Roberts, Richard T; Rotstein, David; San Pablo, Bong; Sarma, Keshab; Stahl, Martin; Sung, Man-Ling; Suttman, Rebecca T; Sjogren, Eric B; Tan, Yunchou; Trejo, Alejandra; Welch, Mary; Weller, Paul; Wong, Brian R; Zecic, Hasim.

Affiliation

Goldstein DM; Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, California 94304, United States. David-M.Goldstein@roche.com

J Med Chem ; 54(7): 2255-65, 2011 Apr 14.

Article in En | MEDLINE | ID: mdl-21375264

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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pyridones / Pyrimidines / Mitogen-Activated Protein Kinase 14 / Drug Discovery Limits: Humans Language: En Journal: J Med Chem Journal subject: QUIMICA Year: 2011 Document type: Article Affiliation country: Estados Unidos

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