Discovery and Optimization of Quinazolinone-pyrrolopyrrolones as Potent and Orally Bioavailable Pan-Pim Kinase Inhibitors.

Autor: Pettus LH; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Andrews KL; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Booker SK; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Chen J; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Cee VJ; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Chavez F Jr; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Chen Y; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Eastwood H; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Guerrero N; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Herberich B; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Hickman D; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Lanman BA; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Laszlo J 3rd; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Lee MR; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Lipford JR; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Mattson B; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Mohr C; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Nguyen Y; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Norman MH; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Powers D; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Reed AB; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Rex K; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Sastri C; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Tamayo N; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Wang P; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Winston JT; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Wu B; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Wu T; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Wurz RP; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Xu Y; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Zhou Y; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Tasker AS; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States., Wang HL; Department of Therapeutic Discovery-Medicinal Chemistry, ‡Molecular Structure, §Pharmacokinetics and Drug Metabolism, ∥Oncology Research, ⊥Pharmaceutics, #Discovery Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2016 Jul 14; Vol. 59 (13), pp. 6407-30. Date of Electronic Publication: 2016 Jun 22.

The discovery of novel 3-(pyrazin-2-yl)-1H-indazoles as potent pan-Pim kinase inhibitors.

Autor: Wang HL; Department of Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. Electronic address: huiw@amgen.com., Cee VJ; Department of Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. Electronic address: vcee@amgen.com., Chavez F Jr; Department of Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA., Lanman BA; Department of Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA., Reed AB; Department of Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA., Wu B; Department of Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA., Guerrero N; Department of Oncology, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA., Lipford JR; Department of Oncology, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA., Sastri C; Department of Oncology, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA., Winston J; Department of Oncology, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA., Andrews KL; Department of Molecular Structure and Characterization, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA., Huang X; Department of Molecular Structure and Characterization, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA., Lee MR; Department of Molecular Structure and Characterization, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA., Mohr C; Department of Molecular Structure and Characterization, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA., Xu Y; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA., Zhou Y; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA., Tasker AS; Department of Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA.

Publikováno v: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2015 Feb 15; Vol. 25 (4), pp. 834-40. Date of Electronic Publication: 2014 Dec 30.

Discovery of 2-methylpyridine-based biaryl amides as γ-secretase modulators for the treatment of Alzheimer's disease.

Autor: Chen JJ; Department of Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States. Electronic address: jianc@amgen.com., Qian W, Biswas K, Yuan C, Amegadzie A, Liu Q, Nixey T, Zhu J, Ncube M, Rzasa RM, Chavez F Jr, Chen N, DeMorin F, Rumfelt S, Tegley CM, Allen JR, Hitchcock S, Hungate R, Bartberger MD, Zalameda L, Liu Y, McCarter JD, Zhang J, Zhu L, Babu-Khan S, Luo Y, Bradley J, Wen PH, Reid DL, Koegler F, Dean C Jr, Hickman D, Correll TL, Williamson T, Wood S

Publikováno v: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2013 Dec 01; Vol. 23 (23), pp. 6447-54. Date of Electronic Publication: 2013 Sep 29.