Zhili Xin

Summary

Affiliation: Biogen Idec
Country: USA

Publications

  1. doi request reprint Discovery of 4-aminomethylphenylacetic acids as γ-secretase modulators via a scaffold design approach
    Zhili Xin
    Department of Medicinal Chemistry, Biogen Idec Inc, 14 Cambridge Center, Cambridge, MA 02142, USA
    Bioorg Med Chem Lett 21:7277-80. 2011
  2. doi request reprint Discovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors
    Zhili Xin
    Abbott Laboratories, Global Pharmaceutical Research and Development, 100 Abbott Road, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 18:4298-302. 2008
  3. ncbi request reprint Selective protein tyrosine phosphatase 1B inhibitors: targeting the second phosphotyrosine binding site with non-carboxylic acid-containing ligands
    Gang Liu
    Metabolic Disease Research and Advanced Technology, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6098, USA
    J Med Chem 46:3437-40. 2003
  4. ncbi request reprint Aminopyridine carboxamides as c-Jun N-terminal kinase inhibitors: targeting the gatekeeper residue and beyond
    Gang Liu
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6101, USA
    Bioorg Med Chem Lett 16:5723-30. 2006
  5. ncbi request reprint Fragment screening and assembly: a highly efficient approach to a selective and cell active protein tyrosine phosphatase 1B inhibitor
    Gang Liu
    Metabolic Disease Research and Advanced Technology, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6098, USA
    J Med Chem 46:4232-5. 2003
  6. ncbi request reprint Structure-activity relationship studies on tetralin carboxamide growth hormone secretagogue receptor antagonists
    Hongyu Zhao
    Metabolic Disease Research, Global Pharmaceutical Research and Development, R4MC, AP 10, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6098, USA
    Bioorg Med Chem Lett 15:1825-8. 2005
  7. ncbi request reprint Discovery and pharmacological evaluation of growth hormone secretagogue receptor antagonists
    Zhili Xin
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6098, USA
    J Med Chem 49:4459-69. 2006
  8. ncbi request reprint Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors
    Hongyu Zhao
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6098, USA
    Bioorg Med Chem Lett 14:5543-6. 2004
  9. ncbi request reprint Potent, selective inhibitors of protein tyrosine phosphatase 1B
    Zhili Xin
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6098, USA
    Bioorg Med Chem Lett 13:1887-90. 2003
  10. ncbi request reprint 2,4-diaminopyrimidine derivatives as potent growth hormone secretagogue receptor antagonists
    Michael D Serby
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6098, USA
    J Med Chem 49:2568-78. 2006

Detail Information

Publications26

  1. doi request reprint Discovery of 4-aminomethylphenylacetic acids as γ-secretase modulators via a scaffold design approach
    Zhili Xin
    Department of Medicinal Chemistry, Biogen Idec Inc, 14 Cambridge Center, Cambridge, MA 02142, USA
    Bioorg Med Chem Lett 21:7277-80. 2011
    ..Further SAR studies provided analog 6q that exhibited a good pharmacological profile. Oral administration of 6q significantly reduced brain Aβ42 levels in mice and rats...
  2. doi request reprint Discovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors
    Zhili Xin
    Abbott Laboratories, Global Pharmaceutical Research and Development, 100 Abbott Road, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 18:4298-302. 2008
    ..4-(2-Chlorophenoxy)-N-[3-(methyl carbamoyl)phenyl]piperidine-1-carboxamide 4c exhibited robust in vivo activity with dose-dependent desaturation index lowering effects...
  3. ncbi request reprint Selective protein tyrosine phosphatase 1B inhibitors: targeting the second phosphotyrosine binding site with non-carboxylic acid-containing ligands
    Gang Liu
    Metabolic Disease Research and Advanced Technology, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6098, USA
    J Med Chem 46:3437-40. 2003
    ....
  4. ncbi request reprint Aminopyridine carboxamides as c-Jun N-terminal kinase inhibitors: targeting the gatekeeper residue and beyond
    Gang Liu
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6101, USA
    Bioorg Med Chem Lett 16:5723-30. 2006
    ..The syntheses of analogues and the impact of structural modification on in vitro potency and cellular activity are described...
  5. ncbi request reprint Fragment screening and assembly: a highly efficient approach to a selective and cell active protein tyrosine phosphatase 1B inhibitor
    Gang Liu
    Metabolic Disease Research and Advanced Technology, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6098, USA
    J Med Chem 46:4232-5. 2003
    ....
  6. ncbi request reprint Structure-activity relationship studies on tetralin carboxamide growth hormone secretagogue receptor antagonists
    Hongyu Zhao
    Metabolic Disease Research, Global Pharmaceutical Research and Development, R4MC, AP 10, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6098, USA
    Bioorg Med Chem Lett 15:1825-8. 2005
    ..It was found that certain 2-alkoxycarbonylamino substituted tetralin carboxamides are potent, selective, and orally bioavailable GHS-R antagonists...
  7. ncbi request reprint Discovery and pharmacological evaluation of growth hormone secretagogue receptor antagonists
    Zhili Xin
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6098, USA
    J Med Chem 49:4459-69. 2006
    ..These observations demonstrated for the first time that peripheral GHS-R blockage with small molecule GHS-R antagonists might not be sufficient for suppressing appetite and inducing body weight reduction...
  8. ncbi request reprint Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors
    Hongyu Zhao
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6098, USA
    Bioorg Med Chem Lett 14:5543-6. 2004
    ..Inhibitor 7 demonstrated good cellular activity against PTP1B in COS 7 cells...
  9. ncbi request reprint Potent, selective inhibitors of protein tyrosine phosphatase 1B
    Zhili Xin
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6098, USA
    Bioorg Med Chem Lett 13:1887-90. 2003
    ....
  10. ncbi request reprint 2,4-diaminopyrimidine derivatives as potent growth hormone secretagogue receptor antagonists
    Michael D Serby
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6098, USA
    J Med Chem 49:2568-78. 2006
    ..A structure-activity relationship study led to the discovery of 8a, which was effective in decreasing food intake and body weight in several acute rat studies...
  11. ncbi request reprint Discovery of potent, highly selective, and orally bioavailable pyridine carboxamide c-Jun NH2-terminal kinase inhibitors
    Hongyu Zhao
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6098, USA
    J Med Chem 49:4455-8. 2006
    ..In this report, we disclose a series of potent and highly selective JNK inhibitors with good pharmacokinetic profiles...
  12. ncbi request reprint Identification of a monoacid-based, cell permeable, selective inhibitor of protein tyrosine phosphatase 1B
    Zhili Xin
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6098, USA
    Bioorg Med Chem Lett 13:3947-50. 2003
    ....
  13. ncbi request reprint Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity
    Bruce G Szczepankiewicz
    Metabolic Disease Research, Global Pharmaceutical Research and Discovery Organization, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6098, USA
    J Med Chem 49:3563-80. 2006
    ..The new compounds were over 1,000-fold selective for JNK-1 and -2 over other MAP kinases including ERK2, p38alpha, and p38delta and showed little inhibitory activity against a panel of 74 kinases...
  14. ncbi request reprint Synthesis and structure-activity relationships of isoxazole carboxamides as growth hormone secretagogue receptor antagonists
    Zhili Xin
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6098, USA
    Bioorg Med Chem Lett 15:1201-4. 2005
    ..A series of isoxazole carboxamide derivatives has been developed as potent ghrelin receptor antagonists. The synthesis and structure-activity relationship (SAR) are described...
  15. ncbi request reprint Optimization of 2,4-diaminopyrimidines as GHS-R antagonists: side chain exploration
    Bo Liu
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6098, USA
    Bioorg Med Chem Lett 16:1864-8. 2006
    ..Diaminopyrimidines with 6-norbornenyl (4n) and 6-tetrahydrofuranyl (4p) substitutents were found to exhibit potent GHS-R antagonism and good selectivity (approximately 1000-fold) against dihydrofolate reductase...
  16. ncbi request reprint Discovery of potent, selective, orally bioavailable stearoyl-CoA desaturase 1 inhibitors
    Gang Liu
    Metabolic Disease Research, Drug Metabolism, Advanced Technology, Exploratory Pharmacokinetics, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064 6101, USA
    J Med Chem 50:3086-100. 2007
    ..The representative lead inhibitor 28c also demonstrates excellent cellular activity in blocking the conversion of saturated long-chain fatty acid-CoAs (LCFA-CoAs) to monounsaturated LCFA-CoAs in HepG2 cells...
  17. ncbi request reprint Discovery of tetralin carboxamide growth hormone secretagogue receptor antagonists via scaffold manipulation
    Hongyu Zhao
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6098, USA
    J Med Chem 47:6655-7. 2004
    ..Union of rational design and high throughput synthesis provided a quick access to high quality chemical leads...
  18. ncbi request reprint Synthesis and SAR of 1,9-dihydro-9-hydroxypyrazolo[3,4-b]quinolin-4-ones as novel, selective c-Jun N-terminal kinase inhibitors
    Mei Liu
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6098, USA
    Bioorg Med Chem Lett 16:2590-4. 2006
    ..The structure-activity relationships (SAR) and kinase selectivity profile of the inhibitors are also discussed. Compound 16 was identified as a potent JNK inhibitor with good cellular potency...
  19. ncbi request reprint Structure-activity relationships for a novel series of thiazolyl phenyl ether derivatives exhibiting potent and selective acetyl-CoA carboxylase 2 inhibitory activity
    Richard F Clark
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 16:6078-81. 2006
    ..Preliminary efforts to optimize the series through modification of the distal aryl ether moiety of the lead scaffold resulted in the identification of compounds exhibiting low-nanomolar potency and isozyme-selective ACC2 activity...
  20. ncbi request reprint Discovery and structure-activity relationship of oxalylarylaminobenzoic acids as inhibitors of protein tyrosine phosphatase 1B
    Gang Liu
    Metabolic Disease Research and Advanced Technology, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064 6098, USA
    J Med Chem 46:2093-103. 2003
    ..Interestingly, oral biovailability has been observed in rats for some compounds. Furthermore, we demonstrated in vivo plasma glucose lowering effects with compound 12d in ob/ob mice...
  21. ncbi request reprint Hemodynamic effects of potent and selective JNK inhibitors in anesthetized rats: implication for targeting protein kinases in metabolic diseases
    Gang Liu
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6101, USA
    Bioorg Med Chem Lett 17:495-500. 2007
    ..The effects of these agents on mean arterial pressure, heart rate, cardiac contractility, and peripheral vascular resistance are described, and the implication for targeting protein kinases in metabolic diseases is discussed...
  22. ncbi request reprint Novel isoxazole carboxamides as growth hormone secretagogue receptor (GHS-R) antagonists
    Bo Liu
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6098, USA
    Bioorg Med Chem Lett 14:5223-6. 2004
    ..A potent analogue (32) with high aqueous solubility and good GPCR selectivity was also identified as a potential pharmacological tool for in vivo studies...
  23. doi request reprint Acceleration of Petasis reactions of salicylaldehyde derivatives with molecular sieves
    Xianglin Shi
    Biogen Idec, 14 Cambridge Center, Cambridge, Massachusetts 02142, USA
    J Org Chem 77:1154-60. 2012
    ..The conditions were applied to the synthesis of the core structure of BIIB042, a γ-secretase modulator, without stereochemical erosion of a stereogenic center in the salicylaldehyde intermediate...
  24. ncbi request reprint Synthesis and structure-activity relationships of N-{3-[2-(4-alkoxyphenoxy)thiazol-5-yl]-1- methylprop-2-ynyl}carboxy derivatives as selective acetyl-CoA carboxylase 2 inhibitors
    Yu Gui Gu
    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, Illinois 60064, USA
    J Med Chem 49:3770-3. 2006
    ..S)-Enantiomer 9p exhibited high ACC2 activity and lowered muscle malonyl-CoA dose-dependently in acute rodent studies, whereas (R)-enantiomer 9o was weak and had no effect on the malonyl-CoA level...
  25. doi request reprint Discovery and characterization of non-ATP site inhibitors of the mitogen activated protein (MAP) kinases
    Kenneth M Comess
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, United States
    ACS Chem Biol 6:234-44. 2011
    ..Together, the data suggest that these new ligand series bind to a novel, allosteric, and physiologically relevant site and therefore represent a unique approach to identify kinase inhibitors...
  26. ncbi request reprint Discovery of a potent, selective protein tyrosine phosphatase 1B inhibitor using a linked-fragment strategy
    Bruce G Szczepankiewicz
    Metabolic Disease Research, Global Pharmaceutical Research and Development Organization, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA
    J Am Chem Soc 125:4087-96. 2003
    ..The modular approach to drug design described in this work should be applicable for the design of potent and selective inhibitors of other therapeutically relevant protein tyrosine phosphatases...