Your browser doesn't support javascript.
loading
Discovery of Potent and Simplified Piperidinone-Based Inhibitors of the MDM2-p53 Interaction.
Yu, Ming; Wang, Yingcai; Zhu, Jiang; Bartberger, Michael D; Canon, Jude; Chen, Ada; Chow, David; Eksterowicz, John; Fox, Brian; Fu, Jiasheng; Gribble, Michael; Huang, Xin; Li, Zhihong; Liu, Jiwen Jim; Lo, Mei-Chu; McMinn, Dustin; Oliner, Jonathan D; Osgood, Tao; Rew, Yosup; Saiki, Anne Y; Shaffer, Paul; Yan, Xuelei; Ye, Qiuping; Yu, Dongyin; Zhao, Xiaoning; Zhou, Jing; Olson, Steven H; Medina, Julio C; Sun, Daqing.
Afiliação
  • Yu M; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Wang Y; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Zhu J; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Bartberger MD; Departments of Therapeutic Discovery and Oncology Research, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
  • Canon J; Departments of Therapeutic Discovery and Oncology Research, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
  • Chen A; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Chow D; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Eksterowicz J; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Fox B; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Fu J; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Gribble M; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Huang X; Department of Therapeutic Discovery, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States.
  • Li Z; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Liu JJ; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Lo MC; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • McMinn D; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Oliner JD; Departments of Therapeutic Discovery and Oncology Research, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
  • Osgood T; Departments of Therapeutic Discovery and Oncology Research, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
  • Rew Y; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Saiki AY; Departments of Therapeutic Discovery and Oncology Research, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
  • Shaffer P; Department of Therapeutic Discovery, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States.
  • Yan X; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Ye Q; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Yu D; Departments of Therapeutic Discovery and Oncology Research, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
  • Zhao X; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Zhou J; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Olson SH; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Medina JC; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Sun D; Departments of Therapeutic Discovery and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
ACS Med Chem Lett ; 5(8): 894-9, 2014 Aug 14.
Article em En | MEDLINE | ID: mdl-25147610
ABSTRACT
Continued optimization of the N-substituent in the piperidinone series provided potent piperidinone-pyridine inhibitors 6, 7, 14, and 15 with improved pharmacokinetic properties in rats. Reducing structure complexity of the N-alkyl substituent led to the discovery of 23, a potent and simplified inhibitor of MDM2. Compound 23 exhibits excellent pharmacokinetic properties and substantial in vivo antitumor activity in the SJSA-1 osteosarcoma xenograft mouse model.
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2014 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2014 Tipo de documento: Article