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. ncbi 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. ncbi 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. ncbi 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. ncbi 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. ncbi 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. ncbi 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
  10. ncbi Finding the perfect spot for fluorine: Improving potency up to 40-fold during a rational fluorine scan of a Bruton's Tyrosine Kinase (BTK) inhibitor scaffold
    Yan Lou
    Hoffmann La Roche Inc, pRED, Pharma Research and Early Development, Small Molecule Research, Discovery Chemistry, 3431 Hillview Ave, Palo Alto, CA 94304, United States Electronic address
    Bioorg Med Chem Lett 25:367-71. 2015

Collaborators

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

Detail Information

Publications10

  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. ncbi 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. ncbi 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. ncbi 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. ncbi 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. ncbi 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. ncbi 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...
  10. ncbi Finding the perfect spot for fluorine: Improving potency up to 40-fold during a rational fluorine scan of a Bruton's Tyrosine Kinase (BTK) inhibitor scaffold
    Yan Lou
    Hoffmann La Roche Inc, pRED, Pharma Research and Early Development, Small Molecule Research, Discovery Chemistry, 3431 Hillview Ave, Palo Alto, CA 94304, United States Electronic address
    Bioorg Med Chem Lett 25:367-71. 2015
    ..Comparison of co-crystal structures of parent molecules and fluorinated counterparts revealed the importance of placing fluorine at the optimal position to achieve favorable interactions with protein side chains. ..