Allan Wissner

Summary

Affiliation: Wyeth Research
Country: USA

Publications

  1. ncbi request reprint Dual irreversible kinase inhibitors: quinazoline-based inhibitors incorporating two independent reactive centers with each targeting different cysteine residues in the kinase domains of EGFR and VEGFR-2
    Allan Wissner
    Chemical and Screening Sciences and Oncology Research, Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, USA
    Bioorg Med Chem 15:3635-48. 2007
  2. ncbi request reprint 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
  3. doi request reprint The development of HKI-272 and related compounds for the treatment of cancer
    Allan Wissner
    Chemical and Screening Sciences, Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, USA
    Arch Pharm (Weinheim) 341:465-77. 2008
  4. ncbi request reprint 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
  5. ncbi request reprint Syntheses and EGFR kinase inhibitory activity of 6-substituted-4-anilino [1,7] and [1,8] naphthyridine-3-carbonitriles
    Allan Wissner
    Chemical and Screening Sciences and Oncology Research, Wyeth Research, 401N Middletown Road, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 14:1411-6. 2004
  6. ncbi request reprint 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
  7. ncbi request reprint 2-(Quinazolin-4-ylamino)-[1,4]benzoquinones as covalent-binding, irreversible inhibitors of the kinase domain of vascular endothelial growth factor receptor-2
    Allan Wissner
    Chemical and Screening Sciences and Oncology Research, Wyeth Research, 401 N Middletown Road, Pearl River, New York 10965, USA
    J Med Chem 48:7560-81. 2005
  8. ncbi request reprint 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
  9. doi request reprint Synthesis and PKCtheta inhibitory activity of a series of 4-indolylamino-5-phenyl-3-pyridinecarbonitriles
    Russell G Dushin
    Wyeth Research, Chemical Sciences, 401 N Middletown Road, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 19:2461-3. 2009
  10. ncbi request reprint Synthesis and evaluation of 4-anilino-6,7-dialkoxy-3-quinolinecarbonitriles as inhibitors of kinases of the Ras-MAPK signaling cascade
    Dan Berger
    Chemical Sciences, Wyeth Research, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 13:3031-4. 2003

Detail Information

Publications17

  1. ncbi request reprint Dual irreversible kinase inhibitors: quinazoline-based inhibitors incorporating two independent reactive centers with each targeting different cysteine residues in the kinase domains of EGFR and VEGFR-2
    Allan Wissner
    Chemical and Screening Sciences and Oncology Research, Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, USA
    Bioorg Med Chem 15:3635-48. 2007
    ..The relative dependence of the IC(50) values on the concentration of ATP used in the assays suggests that these compounds appear to function as irreversible inhibitors of each kinase...
  2. ncbi request reprint 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...
  3. doi request reprint The development of HKI-272 and related compounds for the treatment of cancer
    Allan Wissner
    Chemical and Screening Sciences, Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, USA
    Arch Pharm (Weinheim) 341:465-77. 2008
    ..The promising interim clinical trial results for HKI-272 and EKB-569 in treating colon, lung, and breast cancers are summarized...
  4. ncbi request reprint 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...
  5. ncbi request reprint Syntheses and EGFR kinase inhibitory activity of 6-substituted-4-anilino [1,7] and [1,8] naphthyridine-3-carbonitriles
    Allan Wissner
    Chemical and Screening Sciences and Oncology Research, Wyeth Research, 401N Middletown Road, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 14:1411-6. 2004
    ..Compounds having a 1,7-naphthyridine core structure can retain high potency while those with a 1,8-naphthyridine core are significantly less active. These results are consistent with molecular modeling observations...
  6. ncbi request reprint 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...
  7. ncbi request reprint 2-(Quinazolin-4-ylamino)-[1,4]benzoquinones as covalent-binding, irreversible inhibitors of the kinase domain of vascular endothelial growth factor receptor-2
    Allan Wissner
    Chemical and Screening Sciences and Oncology Research, Wyeth Research, 401 N Middletown Road, Pearl River, New York 10965, USA
    J Med Chem 48:7560-81. 2005
    ..Unequivocal evidence, from mass spectral studies, indicates that these inhibitors form a covalent interaction with Cys-1045. One member of this series displays antitumor activity in an in vivo model...
  8. ncbi request reprint 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...
  9. doi request reprint Synthesis and PKCtheta inhibitory activity of a series of 4-indolylamino-5-phenyl-3-pyridinecarbonitriles
    Russell G Dushin
    Wyeth Research, Chemical Sciences, 401 N Middletown Road, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 19:2461-3. 2009
    ..This study led to the discovery of compound 12d, which had an IC(50) value of 18nM for the inhibition of PKCtheta...
  10. ncbi request reprint Synthesis and evaluation of 4-anilino-6,7-dialkoxy-3-quinolinecarbonitriles as inhibitors of kinases of the Ras-MAPK signaling cascade
    Dan Berger
    Chemical Sciences, Wyeth Research, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 13:3031-4. 2003
    ..Secondary cellular assays revealed that a compound possessing the appropriate aniline substituents inhibited MEK1 as well as MAPK phosphorylation, thereby acting as a dual inhibitor of the Ras-MAPK signaling cascade...
  11. doi request reprint The identification of 8,9-dimethoxy-5-(2-aminoalkoxy-pyridin-3-yl)-benzo[c][2,7]naphthyridin-4-ylamines as potent inhibitors of 3-phosphoinositide-dependent kinase-1 (PDK-1)
    Thomas Nittoli
    Chemical Sciences, Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, USA
    Eur J Med Chem 45:1379-86. 2010
    ....
  12. ncbi request reprint Substituted 4-anilino-7-phenyl-3-quinolinecarbonitriles as Src kinase inhibitors
    Dan Berger
    Chemical Sciences, Wyeth Research, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 12:2989-92. 2002
    ..The best compounds are low nanomolar inhibitors of Src kinase, and have potent activity against Src-transformed fibroblast cells...
  13. doi request reprint Benzo[c][2,7]naphthyridines as inhibitors of PDK-1
    Kyung Hee Kim
    Wyeth Research, Chemical Sciences, 401 N Middletown Road, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 19:5225-8. 2009
    ..The synthesis and SAR of this series of compounds are presented as well as the X-ray crystal structure of one of these analogs in a complex with PDK-1...
  14. ncbi request reprint 8-Anilinoimidazo[4,5-g]quinoline-7-carbonitriles as Src kinase inhibitors
    Dan Berger
    Chemical Sciences, Wyeth Ayerst Research, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 12:2761-5. 2002
    ..Several aniline substituents were surveyed, as well as water-solubilizing groups at the C-2 and N-3 positions. Potent Src inhibitors were identified, with N-3 providing the best position for an additional water-solubilizing group...
  15. ncbi request reprint 4-Anilino-3-cyanobenzo[g]quinolines as kinase inhibitors
    Nan Zhang
    Chemical Sciences, Wyeth Ayerst Research, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 12:423-5. 2002
    ..For Src kinase inhibition, the best activity is obtained when both the 7- and 8-positions are substituted with alkoxy groups. Several of these kinase inhibitors show potent growth inhibitory activity in tumor cells...
  16. doi request reprint Identification, characterization and initial hit-to-lead optimization of a series of 4-arylamino-3-pyridinecarbonitrile as protein kinase C theta (PKCtheta) inhibitors
    Derek C Cole
    Chemical and Screening Sciences, Wyeth Research, Pearl River, New York 10965, USA
    J Med Chem 51:5958-63. 2008
    ..Compound 4p also inhibited IL-2 production in antiCD3/anti-CD28 activated T cells enriched from splenocytes...
  17. pmc Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib
    Eunice L Kwak
    Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
    Proc Natl Acad Sci U S A 102:7665-70. 2005
    ..Our findings suggest that one of these, HKI-272, may prove highly effective in the treatment of EGFR-mutant NSCLCs, including tumors that have become resistant to gefitinib or erlotinib...