Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497)

Pei‐Pei Kung; Martin P. Edwards; Alexei Brooun; Lisa Nguyen; Penney Khamphavong; K.S. Gajiwala; Luke R. Zehnder; Huichun Zhu; Robert S. Kania; Michael R. Collins; Manfred Kraus; Shikhar Sharma; Shuibo Xin; Patrick Bingham; Shinji Yamazaki; Shuiwang Wang; Susan E. Kephart; Robert A. Kumpf; Neal W. Sach; Jillian E. Spangler; Martin Wythes; Hovhannes J. Gukasyan; Karen A. Maegley; Wenyue Hu; Dominique Verhelle; Sean Uryu; Dan Richter; Cody Krivacic; Wei Liu; Hui Wang; Ya‐Li Deng; Scott C. Sutton; JinJiang Zhu; Dac M. Dinh; Albert Stewart; Shijian Ren; John Sherrill; Robert A. Rollins; Rita Grantner; Buwen Huang; Connie Fan

doi:10.1021/acs.jmedchem.7b01375

Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497)

Pei‐Pei Kung(Pfizer (United States)), Martin P. Edwards(Pfizer (United States)), Alexei Brooun(Pfizer (United States)), Lisa Nguyen(Pfizer (United States)), Penney Khamphavong(Pfizer (United States)), K.S. Gajiwala(Pfizer (United States)), Luke R. Zehnder(University of Minnesota), Huichun Zhu(Pfizer (United States)), Robert S. Kania(RG Biopharma (United States)), Michael R. Collins(Pfizer (United States)), Manfred Kraus(Harvard University), Shikhar Sharma(Pfizer (United States)), Shuibo Xin(WuXi AppTec (China)), Patrick Bingham(Pfizer (United States)), Shinji Yamazaki, Shuiwang Wang(WuXi AppTec (China)), Susan E. Kephart(Pfizer (United States)), Robert A. Kumpf(Pfizer (United States)), Neal W. Sach(Pfizer (United States)), Jillian E. Spangler(Scripps Research Institute), Martin Wythes(Pfizer (United States)), Hovhannes J. Gukasyan(Pfizer (United States)), Karen A. Maegley(Pfizer (United States)), Wenyue Hu(Beijing University of Chinese Medicine), Dominique Verhelle(Pfizer (United States)), Sean Uryu(Pfizer (United States)), Dan Richter(Pfizer (United States)), Cody Krivacic(Pfizer (United States)), Wei Liu(Shanghai University of Traditional Chinese Medicine), Hui Wang(Pfizer (United States)), Ya‐Li Deng(Pfizer (United States)), Scott C. Sutton(Pfizer (United States)), JinJiang Zhu(Pfizer (United States)), Dac M. Dinh(Pfizer (United States)), Albert Stewart(Pfizer (United States)), Shijian Ren(WuXi AppTec (China)), John Sherrill(Pfizer (United States)), Robert A. Rollins(Pfizer (United States)), Rita Grantner(Pfizer (United States)), Buwen Huang(Pfizer (United States)), Connie Fan(Pfizer (United States))

Journal of Medicinal Chemistry

December 6, 2017

10.1021/acs.jmedchem.7b01375

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