Neelu Kaila

Summary

Affiliation: Wyeth Research
Country: USA

Publications

  1. ncbi Quinic acid derivatives as sialyl Lewis(x)-mimicking selectin inhibitors: design, synthesis, and crystal structure in complex with E-selectin
    Neelu Kaila
    Chemical and Screening Sciences and Cardiovascular and Metabolic Disease Research, Wyeth, Cambridge, Massachusetts 02140, USA
    J Med Chem 48:4346-57. 2005
  2. ncbi Identification of a novel class of selective Tpl2 kinase inhibitors: 4-Alkylamino-[1,7]naphthyridine-3-carbonitriles
    Neelu Kaila
    Chemical and Screening Sciences, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA
    Bioorg Med Chem 15:6425-42. 2007
  3. ncbi Design and synthesis of sialyl Lewis(x) mimics as E- and P-selectin inhibitors
    Neelu Kaila
    Department of Chemical Sciences and Biological Chemistry, Wyeth, 200 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA
    Med Res Rev 22:566-601. 2002
  4. ncbi 2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[H]quinoline-4-carboxylic acid (PSI-697): identification of a clinical candidate from the quinoline salicylic acid series of P-selectin antagonists
    Neelu Kaila
    Chemical and Screening Sciences, Cardiovascular and Metabolic Disease, Drug Safety and Metabolism, Wyeth Research, Cambridge, Massachusetts 02140, USA
    J Med Chem 50:40-64. 2007
  5. ncbi Synthesis and biological evaluation of quinoline salicylic acids as P-selectin antagonists
    Neelu Kaila
    Chemical and Screening Sciences, Cardiovascular and Metabolic Disease, Drug Safety and Metabolism, Inflammation, Wyeth Research, Cambridge, Massachusetts 02140, USA
    J Med Chem 50:21-39. 2007
  6. ncbi Inhibitors of tumor progression loci-2 (Tpl2) kinase and tumor necrosis factor alpha (TNF-alpha) production: selectivity and in vivo antiinflammatory activity of novel 8-substituted-4-anilino-6-aminoquinoline-3-carbonitriles
    Neal Green
    Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA
    J Med Chem 50:4728-45. 2007
  7. ncbi Discovery of 2-[1-(4-chlorophenyl)cyclopropyl]-3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylic acid (PSI-421), a P-selectin inhibitor with improved pharmacokinetic properties and oral efficacy in models of vascular injury
    Adrian Huang
    Pfizer Global Research and Development, 200 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA
    J Med Chem 53:6003-17. 2010
  8. ncbi Inhibition of Tpl2 kinase and TNFalpha production with quinoline-3-carbonitriles for the treatment of rheumatoid arthritis
    Yonghan Hu
    Department of Chemical and Screening Sciences, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA
    Bioorg Med Chem Lett 16:6067-72. 2006
  9. ncbi Selective inhibitors of tumor progression loci-2 (Tpl2) kinase with potent inhibition of TNF-alpha production in human whole blood
    Junjun Wu
    Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA
    Bioorg Med Chem Lett 19:3485-8. 2009
  10. ncbi Inhibition of Tpl2 kinase and TNF-alpha production with 1,7-naphthyridine-3-carbonitriles: synthesis and structure-activity relationships
    Lori Krim Gavrin
    Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA
    Bioorg Med Chem Lett 15:5288-92. 2005

Detail Information

Publications18

  1. ncbi Quinic acid derivatives as sialyl Lewis(x)-mimicking selectin inhibitors: design, synthesis, and crystal structure in complex with E-selectin
    Neelu Kaila
    Chemical and Screening Sciences and Cardiovascular and Metabolic Disease Research, Wyeth, Cambridge, Massachusetts 02140, USA
    J Med Chem 48:4346-57. 2005
    ..Selected compounds showed decrease in leukocyte rolling in the IVM mouse model. Compound 2 inhibited neutrophil influx in the murine TIP model and demonstrated good plasma exposure...
  2. ncbi Identification of a novel class of selective Tpl2 kinase inhibitors: 4-Alkylamino-[1,7]naphthyridine-3-carbonitriles
    Neelu Kaila
    Chemical and Screening Sciences, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA
    Bioorg Med Chem 15:6425-42. 2007
    ..Lead compound 4-cycloheptylamino-6-[(pyridin-3-ylmethyl)-amino]-[1,7]naphthyridine-3-carbonitrile (30) was efficacious in a rat model of LPS-induced TNF-alpha production...
  3. ncbi Design and synthesis of sialyl Lewis(x) mimics as E- and P-selectin inhibitors
    Neelu Kaila
    Department of Chemical Sciences and Biological Chemistry, Wyeth, 200 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA
    Med Res Rev 22:566-601. 2002
    ....
  4. ncbi 2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[H]quinoline-4-carboxylic acid (PSI-697): identification of a clinical candidate from the quinoline salicylic acid series of P-selectin antagonists
    Neelu Kaila
    Chemical and Screening Sciences, Cardiovascular and Metabolic Disease, Drug Safety and Metabolism, Wyeth Research, Cambridge, Massachusetts 02140, USA
    J Med Chem 50:40-64. 2007
    ..The lead 31 (PSI-697), is currently in clinical development for the treatment of atherothrombotic vascular events...
  5. ncbi Synthesis and biological evaluation of quinoline salicylic acids as P-selectin antagonists
    Neelu Kaila
    Chemical and Screening Sciences, Cardiovascular and Metabolic Disease, Drug Safety and Metabolism, Inflammation, Wyeth Research, Cambridge, Massachusetts 02140, USA
    J Med Chem 50:21-39. 2007
    ..Lead compound 36 was efficacious in the rat AIA model of rheumatoid arthritis...
  6. ncbi Inhibitors of tumor progression loci-2 (Tpl2) kinase and tumor necrosis factor alpha (TNF-alpha) production: selectivity and in vivo antiinflammatory activity of novel 8-substituted-4-anilino-6-aminoquinoline-3-carbonitriles
    Neal Green
    Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA
    J Med Chem 50:4728-45. 2007
    ....
  7. ncbi Discovery of 2-[1-(4-chlorophenyl)cyclopropyl]-3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylic acid (PSI-421), a P-selectin inhibitor with improved pharmacokinetic properties and oral efficacy in models of vascular injury
    Adrian Huang
    Pfizer Global Research and Development, 200 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA
    J Med Chem 53:6003-17. 2010
    ..This compound has shown oral efficacy in animal models of arterial and venous injury and was selected as a preclinical development compound for potential treatment of such diseases as atherosclerosis and deep vein thrombosis...
  8. ncbi Inhibition of Tpl2 kinase and TNFalpha production with quinoline-3-carbonitriles for the treatment of rheumatoid arthritis
    Yonghan Hu
    Department of Chemical and Screening Sciences, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA
    Bioorg Med Chem Lett 16:6067-72. 2006
    ..Selected inhibitors with moderate activity in human whole blood assay effectively inhibited LPS/D-Gal induced TNFalpha release when administered intraperitoneally in mice...
  9. ncbi Selective inhibitors of tumor progression loci-2 (Tpl2) kinase with potent inhibition of TNF-alpha production in human whole blood
    Junjun Wu
    Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA
    Bioorg Med Chem Lett 19:3485-8. 2009
    ..In a LPS-stimulated rat inflammation model, compound 34 showed good efficacy in inhibiting TNF-alpha production...
  10. ncbi Inhibition of Tpl2 kinase and TNF-alpha production with 1,7-naphthyridine-3-carbonitriles: synthesis and structure-activity relationships
    Lori Krim Gavrin
    Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA
    Bioorg Med Chem Lett 15:5288-92. 2005
    ..The early exploratory work described here may lead to the discovery of compounds with significant therapeutic potential for treating rheumatoid arthritis and other inflammatory diseases...
  11. ncbi Beta-C-mannosides as selectin inhibitors
    Neelu Kaila
    Department of Chemical Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA
    J Med Chem 45:1563-6. 2002
    ..Biological evaluation of these compounds was done using two ELISA-based assays and transferred NOE (trNOE) experiments. Some of the compounds showed better activity than sLe(x) in the P-selectin assay...
  12. ncbi Characterization of the novel P-selectin inhibitor PSI-697 [2-(4-chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[h] quinoline-4-carboxylic acid] in vitro and in rodent models of vascular inflammation and thrombosis
    Patricia W Bedard
    Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA
    J Pharmacol Exp Ther 324:497-506. 2008
    ....
  13. ncbi Bromodecarboxylation of quinoline salicylic acids: increasing the diversity of accessible substituted quinolines
    Kristin Janz
    Wyeth Research, Department of Chemical Sciences, 200 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA
    J Org Chem 74:8874-7. 2009
    ..A wide variety of functional groups was tolerated. Several one-pot transformations were also carried out, allowing the preparation of diverse 4-substituted quinolines...
  14. ncbi Selectin inhibitors: a patent review
    Patricia W Bedard
    Pfizer, Biotherapeutics, Biocorrections Research Unit, 200 CambridgePark Drive, Cambridge, MA 02140, USA
    Expert Opin Ther Pat 20:781-93. 2010
    ..Thus, selectins remain attractive targets for amelioration of disease...
  15. ncbi Treatment with an oral small molecule inhibitor of P selectin (PSI-697) decreases vein wall injury in a rat stenosis model of venous thrombosis
    Daniel D Myers
    Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan Medical Center, Ann Arbor, 48109 0654, USA
    J Vasc Surg 44:625-32. 2006
    ....
  16. ncbi Prophylactic P-selectin inhibition with PSI-421 promotes resolution of venous thrombosis without anticoagulation
    Thomas R Meier
    Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    Thromb Haemost 99:343-51. 2008
    ..This study is the first to demonstrate a reduction in MPTFA associated with vein reopening and reduced vein inflammation due to oral P-selectin inhibition in a baboon model of DVT...
  17. ncbi Resolution of venous thrombosis using a novel oral small-molecule inhibitor of P-selectin (PSI-697) without anticoagulation
    Daniel D Myers
    Jobst Vascular Research Laboratories, Section of Vascular Surgery, 2Unit for Laboratory Animal Medicine and 3Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan 48109 0654, USA
    Thromb Haemost 97:400-7. 2007
    ..01). This study is the first to demonstrate the effectiveness of oral P-selectin inhibition to modify venous thrombogenesis, increase vein lumen opening, and decrease inflammation in a large animal model...
  18. ncbi Decreased venous thrombosis with an oral inhibitor of P selectin
    Daniel D Myers
    Section of Vascular Surgery, Jobst Vascular Research Laboratories, Ann Arbor, Mich, USA
    J Vasc Surg 42:329-36. 2005
    ..This study evaluated the effects on thrombosis and circulating microparticle populations in this murine venous thrombosis model...