David M Goldstein

Summary

Affiliation: F. Hoffmann-La Roche Ltd

Publications

  1. ncbi Pathway to the clinic: inhibition of P38 MAP kinase. A review of ten chemotypes selected for development
    David M Goldstein
    Department of Medicinal Chemistry, Roche Palo Alto, 3431 Hillview Ave, Palo Alto, CA 94304, USA
    Curr Top Med Chem 5:1017-29. 2005
  2. doi High-throughput kinase profiling as a platform for drug discovery
    David M Goldstein
    Roche Palo Alto, 3431 Hillview Avenue, R6 201, Palo Alto, California 94304, USA
    Nat Rev Drug Discov 7:391-7. 2008
  3. ncbi Discovery of S-[5-amino-1-(4-fluorophenyl)-1H-pyrazol-4-yl]-[3-(2,3-dihydroxypropoxy)phenyl]methanone (RO3201195), an orally bioavailable and highly selective inhibitor of p38 MAP kinase
    David M Goldstein
    Roche Palo Alto LLC, 3431 Hillview Avenue, R6 123, Palo Alto, California 94304, USA
    J Med Chem 49:1562-75. 2006
  4. doi 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
    David M Goldstein
    Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, California 94304, United States
    J Med Chem 54:2255-65. 2011
  5. ncbi Design and synthesis of 4-azaindoles as inhibitors of p38 MAP kinase
    Alejandra Trejo
    Department of Medicinal Chemistry, Roche Palo Alto LLC, 3431 Hillview Avenue, R6 201, Palo Alto, California 94304, USA
    J Med Chem 46:4702-13. 2003
  6. doi 3-Amino-pyrazolo[3,4-d]pyrimidines as p38α kinase inhibitors: design and development to a highly selective lead
    Michael Soth
    Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304, USA
    Bioorg Med Chem Lett 21:3452-6. 2011
  7. doi Pamapimod, a novel p38 mitogen-activated protein kinase inhibitor: preclinical analysis of efficacy and selectivity
    Ronald J Hill
    Department of Cellular and Molecular Pharmacology, Roche Pharmaceuticals, Palo Alto, CA 94304, USA
    J Pharmacol Exp Ther 327:610-9. 2008
  8. doi Development of amino-pyrimidine inhibitors of c-Jun N-terminal kinase (JNK): kinase profiling guided optimization of a 1,2,3-benzotriazole lead
    Wylie S Palmer
    Roche Palo Alto, 3431 Hillview Ave, Palo Alto, CA 94304, USA
    Bioorg Med Chem Lett 23:1486-92. 2013
  9. doi Modeling bone marrow toxicity using kinase structural motifs and the inhibition profiles of small molecular kinase inhibitors
    Andrew J Olaharski
    Non Clinical Safety, Hoffmann La Roche, Nutley, New Jersey 07110, USA
    Toxicol Sci 118:266-75. 2010

Collaborators

  • Ronald J Hill
  • Stacie A Dalrymple
  • Fujun Li
  • Leyi Gong
  • Anthony M Manning
  • Patrick P Zarrinkar
  • P Dunten
  • David C Swinney
  • Andrew J Olaharski
  • Paul Weller
  • Wylie S Palmer
  • Andreas Kuglstatter
  • Michael Soth
  • Humberto Arzeno
  • Joel Mcintosh
  • Eva Papp
  • Alejandra Trejo
  • Christophe Michoud
  • Humberto B Arzeno
  • Ada Shao
  • James P Dunn
  • Muzaffar Alam
  • Johannes C Hermann
  • Gary Hsieh
  • Cheryl Janson
  • Yun Chou Tan
  • Kung Ching Chang
  • Patricia Tran
  • Linghao Niu
  • Teresa A Trejo-Martin
  • Sue Jin
  • Shao Yong Wu
  • R Ursula Kammlott
  • Tania Silva
  • Deborah C Reuter
  • Alam Jahangir
  • Christine Lukacs
  • Parcharee Tivitmahaisoon
  • Karin Stein
  • Bindu Goyal
  • J Heather Hogg
  • Paul Wagner
  • Roland Billedeau
  • Martin Stahl
  • Kieran Durkin
  • Brian Wong
  • Manjiri Ghate
  • Kristen McCaleb
  • Jaehyeon Park
  • Brad Loe
  • Tobias Gabriel
  • Allassan Abubakari
  • Man Ling Sung
  • Rebecca Suttman
  • Hasim Zecic
  • Nidhi Arora
  • Nolan Dewdney
  • Sandra Frauchiger
  • Sarah Abbot
  • Jennifer Miller
  • Rick Roberts
  • Phyllis E Whiteley
  • Michelle Browner
  • Deborah Reuter
  • Kyung Song
  • Daniel D Comer
  • Florentino Sanpablo
  • Lu Zeng
  • Soan Cheng
  • JoAnn Lafargue
  • Mary Welch
  • Julie Lim
  • Stephen D Warren
  • Sushmita Chanda
  • Armando Villasenor
  • John Saunders
  • Brett Lovejoy
  • Jose Freire-Moar

Detail Information

Publications9

  1. ncbi Pathway to the clinic: inhibition of P38 MAP kinase. A review of ten chemotypes selected for development
    David M Goldstein
    Department of Medicinal Chemistry, Roche Palo Alto, 3431 Hillview Ave, Palo Alto, CA 94304, USA
    Curr Top Med Chem 5:1017-29. 2005
    ..The pharmacology of the Roche compounds is then compared with eight chemically distinct p38 inhibitors known to have entered clinical development...
  2. doi High-throughput kinase profiling as a platform for drug discovery
    David M Goldstein
    Roche Palo Alto, 3431 Hillview Avenue, R6 201, Palo Alto, California 94304, USA
    Nat Rev Drug Discov 7:391-7. 2008
    ..Compound potency and selectivity are determined simultaneously, providing a choice of targets to pursue that is guided by the quality of lead compounds available, rather than by target biology alone...
  3. ncbi Discovery of S-[5-amino-1-(4-fluorophenyl)-1H-pyrazol-4-yl]-[3-(2,3-dihydroxypropoxy)phenyl]methanone (RO3201195), an orally bioavailable and highly selective inhibitor of p38 MAP kinase
    David M Goldstein
    Roche Palo Alto LLC, 3431 Hillview Avenue, R6 123, Palo Alto, California 94304, USA
    J Med Chem 49:1562-75. 2006
    ..These efforts identified 63 (RO3201195) as an orally bioavailable and highly selective inhibitor of p38 which was selected for advancement into Phase I clinical trials...
  4. doi 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
    David M Goldstein
    Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, California 94304, United States
    J Med Chem 54:2255-65. 2011
    ..This manuscript describes the optimization of the lead to p38-selective examples with good pharmacokinetic properties...
  5. ncbi Design and synthesis of 4-azaindoles as inhibitors of p38 MAP kinase
    Alejandra Trejo
    Department of Medicinal Chemistry, Roche Palo Alto LLC, 3431 Hillview Avenue, R6 201, Palo Alto, California 94304, USA
    J Med Chem 46:4702-13. 2003
    ..These efforts identified 42c as a potent inhibitor of p38, which also possessed the required physical properties worthy of advanced studies...
  6. doi 3-Amino-pyrazolo[3,4-d]pyrimidines as p38α kinase inhibitors: design and development to a highly selective lead
    Michael Soth
    Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304, USA
    Bioorg Med Chem Lett 21:3452-6. 2011
    ..Learnings from previous Roche p38-selective inhibitors were applied to a new fragment hit, which was optimized to a potent, exquisitely selective preclinical lead with a good pharmacokinetic profile...
  7. doi Pamapimod, a novel p38 mitogen-activated protein kinase inhibitor: preclinical analysis of efficacy and selectivity
    Ronald J Hill
    Department of Cellular and Molecular Pharmacology, Roche Pharmaceuticals, Palo Alto, CA 94304, USA
    J Pharmacol Exp Ther 327:610-9. 2008
    ..Our study demonstrates that pamapimod is a potent, selective inhibitor of p38alpha with the ability to inhibit the signs and symptoms of RA and other autoimmune diseases...
  8. doi Development of amino-pyrimidine inhibitors of c-Jun N-terminal kinase (JNK): kinase profiling guided optimization of a 1,2,3-benzotriazole lead
    Wylie S Palmer
    Roche Palo Alto, 3431 Hillview Ave, Palo Alto, CA 94304, USA
    Bioorg Med Chem Lett 23:1486-92. 2013
    ....
  9. doi Modeling bone marrow toxicity using kinase structural motifs and the inhibition profiles of small molecular kinase inhibitors
    Andrew J Olaharski
    Non Clinical Safety, Hoffmann La Roche, Nutley, New Jersey 07110, USA
    Toxicol Sci 118:266-75. 2010
    ..A support vector machine classifier was trained on the selected kinases and accurately predicts BMT with 74% accuracy. The model provides an efficient method for understanding SMKI-induced in vivo BMT earlier in drug discovery...