Hwei Ru Tsou

Summary

Affiliation: Wyeth Research
Country: USA

Publications

  1. ncbi Optimization of 6,7-disubstituted-4-(arylamino)quinoline-3-carbonitriles as orally active, irreversible inhibitors of human epidermal growth factor receptor-2 kinase activity
    Hwei Ru Tsou
    Chemical and Screening Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965, USA
    J Med Chem 48:1107-31. 2005
  2. doi Discovery and optimization of 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran-3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR)
    Hwei Ru Tsou
    Chemical Sciences, Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, United States
    Bioorg Med Chem Lett 20:2321-5. 2010
  3. doi 4-Substituted-7-azaindoles bearing a ureidobenzofuranone moiety as potent and selective, ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR)
    Hwei Ru Tsou
    Chemical Sciences, Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, United States
    Bioorg Med Chem Lett 20:2259-63. 2010
  4. doi 4-(Phenylaminomethylene)isoquinoline-1,3(2H,4H)-diones as potent and selective inhibitors of the cyclin-dependent kinase 4 (CDK4)
    Hwei Ru Tsou
    Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, USA
    J Med Chem 51:3507-25. 2008
  5. doi Discovery of 4-(benzylaminomethylene)isoquinoline-1,3-(2H,4H)-diones and 4-[(pyridylmethyl)aminomethylene]isoquinoline-1,3-(2H,4H)-diones as potent and selective inhibitors of the cyclin-dependent kinase 4
    Hwei Ru Tsou
    Chemical and Screening Sciences, and Oncology Research, Wyeth Research, 401 N Middletown Road, Pearl River, New York 10965, USA
    J Med Chem 52:2289-310. 2009
  6. ncbi Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase
    Sridhar K Rabindran
    Department of Oncology, Wyeth Research, Pearl River, New York, USA
    Cancer Res 64:3958-65. 2004
  7. ncbi Synthesis and structure-activity relationships of 6,7-disubstituted 4-anilinoquinoline-3-carbonitriles. The design of an orally active, irreversible inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and the human epi
    Allan Wissner
    Chemical Sciences, Oncology and Immunoinflammatory Research, Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965, USA
    J Med Chem 46:49-63. 2003
  8. ncbi Syntheses and EGFR and HER-2 kinase inhibitory activities of 4-anilinoquinoline-3-carbonitriles: analogues of three important 4-anilinoquinazolines currently undergoing clinical evaluation as therapeutic antitumor agents
    Allan Wissner
    Chemical Sciences and Oncology and Immunoinflammatory Research, Wyeth Research, 401N Middletown Road, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 12:2893-7. 2002
  9. ncbi Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel anti-proliferative agents: parallel synthesis for lead optimization of amide region
    Ariamala Gopalsamy
    Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 15:1591-4. 2005
  10. doi Lead identification to generate isoquinolinedione inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment
    Scott C Mayer
    Wyeth Research, Chemical and Screening Sciences, 865 Ridge Road, Monmouth Junction, Princeton, NJ 08852, USA
    Bioorg Med Chem Lett 18:3641-5. 2008

Detail Information

Publications11

  1. ncbi Optimization of 6,7-disubstituted-4-(arylamino)quinoline-3-carbonitriles as orally active, irreversible inhibitors of human epidermal growth factor receptor-2 kinase activity
    Hwei Ru Tsou
    Chemical and Screening Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965, USA
    J Med Chem 48:1107-31. 2005
    ..Furthermore, it demonstrated excellent oral activity, especially in HER-2 overexpressing xenografts. Compound 25o (HKI-272) was selected for further studies and is currently in phase I clinical trials for the treatment of cancer...
  2. doi Discovery and optimization of 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran-3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR)
    Hwei Ru Tsou
    Chemical Sciences, Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, United States
    Bioorg Med Chem Lett 20:2321-5. 2010
    ..An X-ray co-crystal structure of one inhibitor with the mTOR-related PI3Kgamma revealed the key hydrogen bonding interactions...
  3. doi 4-Substituted-7-azaindoles bearing a ureidobenzofuranone moiety as potent and selective, ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR)
    Hwei Ru Tsou
    Chemical Sciences, Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, United States
    Bioorg Med Chem Lett 20:2259-63. 2010
    ..Furthermore, modeling showed that the ureido group is best situated at C-5 of the benzofuranone. Syntheses of 4-ureido and 5-ureidobenzofuranones are presented...
  4. doi 4-(Phenylaminomethylene)isoquinoline-1,3(2H,4H)-diones as potent and selective inhibitors of the cyclin-dependent kinase 4 (CDK4)
    Hwei Ru Tsou
    Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, USA
    J Med Chem 51:3507-25. 2008
    ..We present here SAR data and a CDK4 mimic model that explains the binding, potency, and selectivity of our CDK4 selective inhibitors...
  5. doi Discovery of 4-(benzylaminomethylene)isoquinoline-1,3-(2H,4H)-diones and 4-[(pyridylmethyl)aminomethylene]isoquinoline-1,3-(2H,4H)-diones as potent and selective inhibitors of the cyclin-dependent kinase 4
    Hwei Ru Tsou
    Chemical and Screening Sciences, and Oncology Research, Wyeth Research, 401 N Middletown Road, Pearl River, New York 10965, USA
    J Med Chem 52:2289-310. 2009
    ..We present here the synthesis, SAR data, metabolic stability data, and a CDK4 mimic model that explains the binding, potency, and selectivity of our CDK4 selective inhibitors...
  6. ncbi Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase
    Sridhar K Rabindran
    Department of Oncology, Wyeth Research, Pearl River, New York, USA
    Cancer Res 64:3958-65. 2004
    ..On the basis of its favorable preclinical pharmacological profile, HKI-272 has been selected as a candidate for additional development as an antitumor agent in breast and other HER-2-dependent cancers...
  7. ncbi Synthesis and structure-activity relationships of 6,7-disubstituted 4-anilinoquinoline-3-carbonitriles. The design of an orally active, irreversible inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and the human epi
    Allan Wissner
    Chemical Sciences, Oncology and Immunoinflammatory Research, Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965, USA
    J Med Chem 46:49-63. 2003
    ..One compound, 5 (EKB-569), which shows excellent oral in vivo activity, was selected for further studies and is currently in phase I clinical trials for the treatment of cancer...
  8. ncbi Syntheses and EGFR and HER-2 kinase inhibitory activities of 4-anilinoquinoline-3-carbonitriles: analogues of three important 4-anilinoquinazolines currently undergoing clinical evaluation as therapeutic antitumor agents
    Allan Wissner
    Chemical Sciences and Oncology and Immunoinflammatory Research, Wyeth Research, 401N Middletown Road, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 12:2893-7. 2002
    ..The EGFR and HER-2 kinase inhibitory activities and the cell growth inhibition of the two series are compared with each other and with the clinical lead EKB-569. Similar activities are observed between these two series...
  9. ncbi Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel anti-proliferative agents: parallel synthesis for lead optimization of amide region
    Ariamala Gopalsamy
    Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 15:1591-4. 2005
    ..The isopropyl carbamate derivative 34 was identified as a highly chemoselective agent displaying a potency of 51 nM in the p21 deficient cell line...
  10. doi Lead identification to generate isoquinolinedione inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment
    Scott C Mayer
    Wyeth Research, Chemical and Screening Sciences, 865 Ridge Road, Monmouth Junction, Princeton, NJ 08852, USA
    Bioorg Med Chem Lett 18:3641-5. 2008
    ..The strategies, synthesis, and SAR behind this interesting kinase scaffold will be described...
  11. ncbi Gemtuzumab ozogamicin, a potent and selective anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia
    Philip R Hamann
    Wyeth Ayerst Research, 401 North Middletown Road, Pearl River, New York 10965, USA
    Bioconjug Chem 13:47-58. 2002
    ..Gem-ozo has also shown significant activity against AML in Phase II trials and is the first antibody-targeted chemotherapeutic agent approved by the FDA...