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. doi Structure-based drug design of RN486, a potent and selective Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of rheumatoid arthritis
    Yan Lou
    pRED, Pharma Research and Early Development, Small Molecule Research, Discovery Chemistry, Hoffmann La Roche Inc, 3431 Hillview Avenue, Palo Alto, California 94304, United States
    J Med Chem 58:512-6. 2015
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  • Fujun Li
  • 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
  • Yan Lou
  • Andreas Kuglstatter
  • Joel Mcintosh
  • Michael Soth
  • Paul Weller
  • Buelent Koçer
  • Junbae Hong
  • Rama K Kondru
  • Keshab Sarma
  • Judy Suh
  • Dana Davis
  • Timothy D Owens
  • Xiaochun Han
  • Renee Litman
  • Tobias Gabriel
  • Jaehyeon Park
  • Sandra Frauchiger
  • Hasim Zecic
  • Wylie S Palmer
  • Nolan Dewdney
  • Eva Papp
  • Humberto Arzeno
  • Alejandra Trejo
  • Joshua P Taygerly
  • Joshua Taygerly
  • Gary Hsieh
  • James P Dunn
  • Johannes C Hermann
  • Ada Shao
  • Alam Jahangir
  • Parcharee Tivitmahaisoon
  • Christine Lukacs
  • Cheryl Janson
  • Shao Yong Wu
  • Kung Ching Chang
  • Sue Jin
  • Bindu Goyal
  • Christophe Michoud
  • Linghao Niu
  • Yun Chou Tan
  • Humberto B Arzeno
  • J Heather Hogg
  • Tania Silva
  • R Ursula Kammlott
  • Paul Wagner
  • Teresa A Trejo-Martin
  • Muzaffar Alam
  • Karin Stein
  • Patricia Tran
  • Deborah C Reuter
  • Brad Loe
  • Manjiri Ghate
  • Nidhi Arora
  • Brian Wong
  • Allassan Abubakari
  • Kieran Durkin
  • Rebecca Suttman
  • Martin Stahl
  • Roland Billedeau
  • Kristen McCaleb
  • Sarah Abbot
  • Man Ling Sung
  • Brett Lovejoy
  • Rick Roberts
  • Armando Villasenor
  • Kyung Song
  • Mary Welch
  • Julie Lim
  • Sushmita Chanda
  • John Saunders
  • Soan Cheng
  • Jennifer Miller
  • Deborah Reuter
  • Daniel D Comer
  • Phyllis E Whiteley
  • Stephen D Warren
  • Lu Zeng
  • Florentino Sanpablo

Detail Information

Publications11

  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. doi Structure-based drug design of RN486, a potent and selective Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of rheumatoid arthritis
    Yan Lou
    pRED, Pharma Research and Early Development, Small Molecule Research, Discovery Chemistry, Hoffmann La Roche Inc, 3431 Hillview Avenue, Palo Alto, California 94304, United States
    J Med Chem 58:512-6. 2015
    ..Concurrent optimization of drug-like properties led to compound 1 (RN486) ( J. Pharmacol. Exp. Ther. 2012 , 341 , 90 ), which was selected for advanced preclinical characterization based on its favorable properties. ..
  6. 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...
  7. 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...
  8. 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...
  9. 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
    ....
  10. 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...
  11. doi 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. ..