Andrew V Stachulski

Summary

Affiliation: University of Liverpool
Country: UK

Publications

  1. ncbi request reprint The chemistry and biological activity of acyl glucuronides
    Andrew V Stachulski
    Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK
    Curr Opin Drug Discov Devel 10:58-66. 2007
  2. ncbi request reprint Effective synthesis of 1beta-acyl glucuronides by selective acylation
    Jennifer A Perrie
    The Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, UK
    Org Lett 7:2591-4. 2005
  3. ncbi request reprint Convenient syntheses of halo-dibenz[b,f]azepines and carbamazepine analogues via N-arylindoles
    Emma Claire Elliott
    Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
    Org Biomol Chem 11:8426-34. 2013
  4. doi request reprint The generation, detection, and effects of reactive drug metabolites
    Andrew V Stachulski
    Department of Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool, L69 7ZD, UK
    Med Res Rev 33:985-1080. 2013
  5. doi request reprint Glucuronides from metabolites to medicines: a survey of the in vivo generation, chemical synthesis and properties of glucuronides
    Andrew V Stachulski
    Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD
    Nat Prod Rep 30:806-48. 2013
  6. ncbi request reprint Acyl glucuronides: biological activity, chemical reactivity, and chemical synthesis
    Andrew V Stachulski
    Department of Chemistry, The Robert Robinson Laboratories, University of Liverpool, Liverpool L69 7ZD, UK
    J Med Chem 49:6931-45. 2006
  7. ncbi request reprint Identification of isoflavone derivatives as effective anticryptosporidial agents in vitro and in vivo
    Andrew V Stachulski
    Romark Centre for Drug Discovery, Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
    J Med Chem 49:1450-4. 2006
  8. doi request reprint Thiazolides as novel antiviral agents. 2. Inhibition of hepatitis C virus replication
    Andrew V Stachulski
    Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
    J Med Chem 54:8670-80. 2011
  9. doi request reprint Synthesis of a series of phenylacetic acid 1-β-O-acyl glucosides and comparison of their acyl migration and hydrolysis kinetics with the corresponding acyl glucuronides
    Lisa Iddon
    Department of Chemistry, The Robert Robinson Laboratories, University of Liverpool, Liverpool, UK L69 7ZD
    Org Biomol Chem 9:926-34. 2011
  10. doi request reprint Synthesis, in vitro and in vivo antimalarial assessment of sulfide, sulfone and vinyl amide-substituted 1,2,4-trioxanes prepared via thiol-olefin co-oxygenation (TOCO) of allylic alcohols
    Richard Amewu
    Department of Chemistry, University of Liverpool, P O Box 147, Liverpool, UK L69 3BX
    Org Biomol Chem 8:2068-77. 2010

Collaborators

Detail Information

Publications31

  1. ncbi request reprint The chemistry and biological activity of acyl glucuronides
    Andrew V Stachulski
    Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK
    Curr Opin Drug Discov Devel 10:58-66. 2007
    ..The chemical and biological reactivity of AGs are then discussed, and recent case studies of carboxylic acid therapeutics spanning a range of therapeutic areas are tabulated...
  2. ncbi request reprint Effective synthesis of 1beta-acyl glucuronides by selective acylation
    Jennifer A Perrie
    The Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, UK
    Org Lett 7:2591-4. 2005
    ..The method is effective for a range of aryl and alkyl carboxylic acids, including important drugs...
  3. ncbi request reprint Convenient syntheses of halo-dibenz[b,f]azepines and carbamazepine analogues via N-arylindoles
    Emma Claire Elliott
    Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
    Org Biomol Chem 11:8426-34. 2013
    ..The 5-(carboxamido) side chain of carbamazepine may be added in various ways, affording overall a convenient access to drug molecules. ..
  4. doi request reprint The generation, detection, and effects of reactive drug metabolites
    Andrew V Stachulski
    Department of Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool, L69 7ZD, UK
    Med Res Rev 33:985-1080. 2013
    ..Finally, we discuss the impact of such data on the drug discovery process, both through early detection of reactive metabolites and informed synthetic design, which eliminates unfavorable functionality from drug candidates. ..
  5. doi request reprint Glucuronides from metabolites to medicines: a survey of the in vivo generation, chemical synthesis and properties of glucuronides
    Andrew V Stachulski
    Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD
    Nat Prod Rep 30:806-48. 2013
    ..We summarise the current understanding, together with other known examples of interaction between glucuronides and macromolecules...
  6. ncbi request reprint Acyl glucuronides: biological activity, chemical reactivity, and chemical synthesis
    Andrew V Stachulski
    Department of Chemistry, The Robert Robinson Laboratories, University of Liverpool, Liverpool L69 7ZD, UK
    J Med Chem 49:6931-45. 2006
  7. ncbi request reprint Identification of isoflavone derivatives as effective anticryptosporidial agents in vitro and in vivo
    Andrew V Stachulski
    Romark Centre for Drug Discovery, Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
    J Med Chem 49:1450-4. 2006
    ..Excellent in vitro activity against Cryptosporidium parvum was observed for both classes of isoflavones in cell cultures, and the lead compound 19, RM6427, shows high in vivo efficacy against an experimental infection...
  8. doi request reprint Thiazolides as novel antiviral agents. 2. Inhibition of hepatitis C virus replication
    Andrew V Stachulski
    Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
    J Med Chem 54:8670-80. 2011
    ..We conclude by updating the mode of action of the thiazolides and explain the candidate selection that has led to compound 4 entering preclinical development...
  9. doi request reprint Synthesis of a series of phenylacetic acid 1-β-O-acyl glucosides and comparison of their acyl migration and hydrolysis kinetics with the corresponding acyl glucuronides
    Lisa Iddon
    Department of Chemistry, The Robert Robinson Laboratories, University of Liverpool, Liverpool, UK L69 7ZD
    Org Biomol Chem 9:926-34. 2011
    ....
  10. doi request reprint Synthesis, in vitro and in vivo antimalarial assessment of sulfide, sulfone and vinyl amide-substituted 1,2,4-trioxanes prepared via thiol-olefin co-oxygenation (TOCO) of allylic alcohols
    Richard Amewu
    Department of Chemistry, University of Liverpool, P O Box 147, Liverpool, UK L69 3BX
    Org Biomol Chem 8:2068-77. 2010
    ..Selected analogues express potent in vitro nM antimalarial activity, low cytotoxicity and oral activity in the Plasmodium berghei mouse model of malaria...
  11. pmc Direct evidence for the formation of diastereoisomeric benzylpenicilloyl haptens from benzylpenicillin and benzylpenicillenic acid in patients
    Xiaoli Meng
    Medical Research Council Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom
    J Pharmacol Exp Ther 338:841-9. 2011
    ..Furthermore, PA was found to be more potent than BP with respect to stimulation of T cells from patients with penicillin hypersensitivity, illustrating the functional relevance of diastereoisomeric hapten formation...
  12. doi request reprint Convenient syntheses of benzo-fluorinated dibenz[b,f]azepines: rearrangements of isatins, acridines, and indoles
    Emma Claire Elliott
    Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
    Org Lett 13:5592-5. 2011
    ..A range of mono- and difluorinated analogues is accessible, and the syntheses can deliver gram quantities of the final products, which are precursors of fluoro analogues of the important anticonvulsant carbamazepine...
  13. ncbi request reprint Design and synthesis of orally active dispiro 1,2,4,5-tetraoxanes; synthetic antimalarials with superior activity to artemisinin
    Richard Amewu
    Department of Chemistry, University of Liverpool, PO Box 147, Liverpool, UK L69 3BX
    Org Biomol Chem 4:4431-6. 2006
    ..Several analogues display an unprecedented level of oral antimalarial activity for this class of endoperoxide drug...
  14. doi request reprint Haloarene derivatives of carbamazepine with reduced bioactivation liabilities: 2-monohalo and 2,8-dihalo derivatives
    Emma Claire Elliott
    Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, U K
    J Med Chem 55:9773-84. 2012
    ..Complete inhibition of aromatic hydroxylation required at least monochlorination or difluorination of 1. In human liver microsomes, difluoro analogue 5b underwent 10,11-epoxidation but gave no arene oxidation...
  15. doi request reprint Modular synthesis and in vitro and in vivo antimalarial assessment of C-10 pyrrole mannich base derivatives of artemisinin
    Bénédicte Pacorel
    Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
    J Med Chem 53:633-40. 2010
    ....
  16. doi request reprint Synthesis, transacylation kinetics and computational chemistry of a set of arylacetic acid 1beta-O-acyl glucuronides
    Neil G Berry
    Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool, UK L69 7ZD
    Org Biomol Chem 7:2525-33. 2009
    ....
  17. ncbi request reprint Synthesis of 1,2,4-trioxepanes via application of thiol-olefin co-oxygenation methodology
    Richard Amewu
    Department of Chemistry, University of Liverpool, PO Box 147, Liverpool L69 3BX, UK
    Bioorg Med Chem Lett 16:6124-30. 2006
    ..FMO calculations clearly show that the sigma* orbital of the peroxide moiety of 1,2,4-trioxane derivatives 4a and 14b are lower in energy and more accessible to attack by Fe(II) compared to their trioxepane analogues 8b and 9b...
  18. ncbi request reprint The acyl nitroso Diels-Alder (ANDA) reaction of sorbate derivatives: an X-ray and 15N NMR study with an application to amino-acid synthesis
    Lee Bollans
    Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK
    Org Biomol Chem 7:4531-8. 2009
    ..We present single-crystal X-ray structural proof for key adducts in both series and present in detail a novel HMBC/HSQC ((1)H-(15)N) criterion for ready distinction of regioisomers arising from such ANDA reactions...
  19. ncbi request reprint Cyclization of the acyl glucuronide metabolite of a neutral endopeptidase inhibitor to an electrophilic glutarimide: synthesis, reactivity, and mechanistic analysis
    Xiaoli Meng
    The Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool, United Kingdom
    J Med Chem 50:6165-76. 2007
    ..76). N-propyl 3 was refractory to acyl migration and cyclization. This suggested a synthetic strategy for preparing analogues of 2 that form chemically stable acyl glucuronides...
  20. ncbi request reprint Investigation of the immunogenicity of diclofenac and diclofenac metabolites
    Dean J Naisbitt
    Department of Pharmacology, The Sherrington Building, Ashton Street, The University of Liverpool, Liverpool, UK
    Toxicol Lett 168:45-50. 2007
    ..These data show that formation of 5-hydroxy DCF and subsequent autoxidation provides an antigenic determinant for immune cell activation in the mouse...
  21. pmc Thiazolides as novel antiviral agents. 1. Inhibition of hepatitis B virus replication
    Andrew V Stachulski
    Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
    J Med Chem 54:4119-32. 2011
    ..The QSAR study shows a good correlation of observed EC(90) for intracellular virions with thiazolide structural parameters. Finally we discuss the mechanism of action of thiazolides in relation to the present results...
  22. ncbi request reprint Mass spectrometric characterization of circulating covalent protein adducts derived from a drug acyl glucuronide metabolite: multiple albumin adductions in diclofenac patients
    Thomas G Hammond
    Medical Research Council Centre for Drug Safety Science, Institute of Translational Medicine, T G H, X M, R E J, J L M, A S C, S L R, C J E, B K P, D P W and Department of Chemistry A V S, University of Liverpool, Liverpool, United Kingdom Nottingham Digestive Diseases Centre, NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham G P A and Department of Rheumatology, Nottingham University Hospitals NHS Trust I P, Nottingham, United Kingdom and AstraZeneca U K Ltd S N L B and Safety Assessment, AstraZeneca U K Ltd J G K, Alderley Park, Macclesfield, Cheshire, United Kingdom
    J Pharmacol Exp Ther 350:387-402. 2014
    ....
  23. ncbi request reprint Chemistry and reactivity of acyl glucuronides
    Andrew V Stachulski
    Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
    Curr Drug Metab 12:215-21. 2011
    ..This pathway may lead to different protein reactivity than shown for AGs themselves, including interference with the glutathione pathway as shown for NSAID-like carboxylic acids...
  24. ncbi request reprint Activation of T cells by carbamazepine and carbamazepine metabolites
    Ying Wu
    Department of Pharmacology, University of Liverpool, Ashton Street, Liverpool L69 3GE, UK
    J Allergy Clin Immunol 118:233-41. 2006
    ..T-cell-mediated hypersensitivity is a rare but serious manifestation of drug therapy...
  25. ncbi request reprint Glycosidation with a disarmed glycosyl iodide: promotion and scope
    Jennifer A Perrie
    The Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool L 69 7 ZD, UK
    Org Lett 5:4545-8. 2003
    ..Various "nonheavy" metal salts also effectively catalyzed the model reaction but led to significant amounts of alpha-product with less reactive secondary alcohols...
  26. ncbi request reprint NMR spectroscopic studies on the in vitro acyl glucuronide migration kinetics of Ibuprofen ((+/-)-(R,S)-2-(4-isobutylphenyl) propanoic acid), its metabolites, and analogues
    Caroline H Johnson
    Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics SORA, Faculty of Medicine, Imperial College London, South Kensington, London SW7 2AZ, U K
    Anal Chem 79:8720-7. 2007
    ..The implications of these findings are discussed in terms of structure-activity relationships...
  27. doi request reprint Kinetic and J-resolved statistical total correlation NMR spectroscopy approaches to structural information recovery in complex reacting mixtures: application to acyl glucuronide intramolecular transacylation reactions
    Caroline H Johnson
    Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Sir Alexander Fleming Building, Imperial College London, South Kensington, London SW7 2AZ, UK
    Anal Chem 80:4886-95. 2008
    ..JRES-STOCSY is also of potential use as a method for recovering spectroscopic information in highly overlapped NMR signals and spin systems in other types of complex mixture analysis...
  28. ncbi request reprint Glucuronidation of steroidal alcohols using iodosugar and imidate donors
    John R Harding
    AstraZeneca UK Ltd, Drug Metabolism and Pharmacokinetics Department, Mereside, Cheshire, UK
    Org Biomol Chem 3:1501-7. 2005
    ..derivatives 2 and 3), Lewis acid catalyst and order of addition. The results are contrasted with those obtained using our recently described glycosyl iodide donor 4, catalysed either by N-iodosuccinimide (NIS) or various metal salts...
  29. ncbi request reprint Syntheses and characterization of the acyl glucuronide and hydroxy metabolites of diclofenac
    Jane R Kenny
    Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 3GE, United Kingdom
    J Med Chem 47:2816-25. 2004
    ..A previously undescribed glutathione adduct of 3 was obtained by enzymatic synthesis. Compound 4 formed an imine-linked protein conjugate as evinced by sodium cyanoborohydride trapping...
  30. ncbi request reprint An unsaturated peptidomimetic assembly derived from a carbohydrate
    Ying Kit Chung
    Dyson Perrins Laboratory, University of Oxford, OX1 3QY, UK
    J Pept Sci 10:1-7. 2004
    ..The 'dimer' product of coupling these two components with TBTU can be similarly elaborated at either end to give a 'trimer' and a further cycle of selective reduction and coupling gave a 'tetramer', 17, a pseudo-octapeptide...
  31. ncbi request reprint Structure-activity relationships of some opiate glycosides
    Andrew V Stachulski
    Ultrafine UFC Ltd, Synergy House, Guildhall Close, Manchester Science Park, Manchester M15 6SY, UK
    Bioorg Med Chem Lett 13:1207-14. 2003
    ..Saturation of the 7,8-double bond led to increased agonism compared to the parent compound in all three examples studied...