Brian D Palmer

Summary

Affiliation: University of Auckland
Country: New Zealand

Publications

  1. ncbi request reprint 4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione inhibitors of the checkpoint kinase Wee1. Structure-activity relationships for chromophore modification and phenyl ring substitution
    Brian D Palmer
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1020, New Zealand
    J Med Chem 49:4896-911. 2006
  2. ncbi request reprint Structure-activity relationships for 2-anilino-6-phenylpyrido[2,3-d]pyrimidin-7(8H)-ones as inhibitors of the cellular checkpoint kinase Wee1
    Brian D Palmer
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    Bioorg Med Chem Lett 15:1931-5. 2005
  3. doi request reprint Structure-activity relationships for amide-, carbamate-, and urea-linked analogues of the tuberculosis drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824)
    Adrian Blaser
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    J Med Chem 55:312-26. 2012
  4. doi request reprint Synthesis and structure-activity studies of biphenyl analogues of the tuberculosis drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824)
    Brian D Palmer
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    J Med Chem 53:282-94. 2010
  5. doi request reprint Synthesis and structure-activity relationships of varied ether linker analogues of the antitubercular drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5h-imidazo[2,1-b][1,3]oxazine (PA-824)
    Andrew M Thompson
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    J Med Chem 54:6563-85. 2011
  6. doi request reprint Synthesis and structure-activity relationships of soluble 8-substituted 4-(2-chlorophenyl)-9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of the Wee1 and Chk1 checkpoint kinases
    Jeff B Smaill
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    Bioorg Med Chem Lett 18:929-33. 2008
  7. doi request reprint Release of nitrite from the antitubercular nitroimidazole drug PA-824 and analogues upon one-electron reduction in protic, non-aqueous solvent
    Andrej Maroz
    Department of Chemistry, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand
    Org Biomol Chem 8:413-8. 2010
  8. doi request reprint Synthesis and structure-activity relationships of antitubercular 2-nitroimidazooxazines bearing heterocyclic side chains
    Hamish S Sutherland
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    J Med Chem 53:855-66. 2010
  9. ncbi request reprint Synthesis and structure-activity relationships of N-6 substituted analogues of 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of Wee1 and Chk1 checkpoint kinases
    Jeff B Smaill
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1020, New Zealand
    Eur J Med Chem 43:1276-96. 2008
  10. pmc Labeling of oxidizable proteins with a photoactivatable analog of the antitumor agent DMXAA: evidence for redox signaling in its mode of action
    Romy Brauer
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
    Neoplasia 12:755-65. 2010

Collaborators

Detail Information

Publications23

  1. ncbi request reprint 4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione inhibitors of the checkpoint kinase Wee1. Structure-activity relationships for chromophore modification and phenyl ring substitution
    Brian D Palmer
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1020, New Zealand
    J Med Chem 49:4896-911. 2006
    ..These studies provide a basis for the design of active analogues of the pyrrolocarbazole lead with improved physical properties...
  2. ncbi request reprint Structure-activity relationships for 2-anilino-6-phenylpyrido[2,3-d]pyrimidin-7(8H)-ones as inhibitors of the cellular checkpoint kinase Wee1
    Brian D Palmer
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    Bioorg Med Chem Lett 15:1931-5. 2005
    ..Solubilizing substituents off the 2-anilino ring in many cases increased Wee1 activity, thus lowering this preference to about 10-fold. 5-Alkyl substituted analogs were generally Wee1 selective, but at the expense of absolute potency...
  3. doi request reprint Structure-activity relationships for amide-, carbamate-, and urea-linked analogues of the tuberculosis drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824)
    Adrian Blaser
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    J Med Chem 55:312-26. 2012
    ....
  4. doi request reprint Synthesis and structure-activity studies of biphenyl analogues of the tuberculosis drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824)
    Brian D Palmer
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    J Med Chem 53:282-94. 2010
    ..In vivo activity correlated well with the stability of compounds to microsomal metabolism. Three compounds bearing combinations of lipophilic, electron-withdrawing groups achieved >200-fold higher efficacies than the parent drug...
  5. doi request reprint Synthesis and structure-activity relationships of varied ether linker analogues of the antitubercular drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5h-imidazo[2,1-b][1,3]oxazine (PA-824)
    Andrew M Thompson
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    J Med Chem 54:6563-85. 2011
    ..One propynyloxy-linked compound displayed an 89-fold higher efficacy than the parent drug in the acute model, and it was slightly superior to antitubercular drug OPC-67683 in a chronic infection model...
  6. doi request reprint Synthesis and structure-activity relationships of soluble 8-substituted 4-(2-chlorophenyl)-9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of the Wee1 and Chk1 checkpoint kinases
    Jeff B Smaill
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    Bioorg Med Chem Lett 18:929-33. 2008
    ..Co-crystal structure studies confirm that the primary binding to the Wee1 enzyme is as described previously, with the C-8 side chains residing in an area of bulk tolerance...
  7. doi request reprint Release of nitrite from the antitubercular nitroimidazole drug PA-824 and analogues upon one-electron reduction in protic, non-aqueous solvent
    Andrej Maroz
    Department of Chemistry, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand
    Org Biomol Chem 8:413-8. 2010
    ..The described radiolytic quantification of nitrite release may have utility as a preliminary screening test for nitroaromatic candidate drugs against the disease...
  8. doi request reprint Synthesis and structure-activity relationships of antitubercular 2-nitroimidazooxazines bearing heterocyclic side chains
    Hamish S Sutherland
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    J Med Chem 53:855-66. 2010
    ..tb than predicted by their lipophilicities. Two pyrazole analogues were >10-fold more efficacious than the parent drug in a mouse model of acute M. tb infection, and one displayed a 2-fold higher solubility...
  9. ncbi request reprint Synthesis and structure-activity relationships of N-6 substituted analogues of 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of Wee1 and Chk1 checkpoint kinases
    Jeff B Smaill
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1020, New Zealand
    Eur J Med Chem 43:1276-96. 2008
    ..HT-29 cells treated with doxorubicin and then target compounds demonstrate an active Cdc2/cyclin B complex, inhibition of the doxorubicin-induced phosphorylation of tyrosine 15 of Cdc2 and abrogation of the G2 checkpoint...
  10. pmc Labeling of oxidizable proteins with a photoactivatable analog of the antitumor agent DMXAA: evidence for redox signaling in its mode of action
    Romy Brauer
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
    Neoplasia 12:755-65. 2010
    ..The results from these lines of study all suggest that redox signaling plays a central role in cytokine induction by DMXAA...
  11. doi request reprint Synthesis, reduction potentials, and antitubercular activity of ring A/B analogues of the bioreductive drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824)
    Andrew M Thompson
    Auckland Cancer Society Research Centre, School of Medical Sciences and Department of Chemistry, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    J Med Chem 52:637-45. 2009
    ....
  12. ncbi request reprint Effect of 3-fluorothalidomide and 3-methylthalidomide enantiomers on tumor necrosis factor production and antitumor responses to the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA)
    Francisco Chung
    Auckland Cancer Society Research Center, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
    Oncol Res 14:75-82. 2003
    ..We conclude that there is no advantage in using the nonracemizable thalidomide analogues to improve the antitumor activity of DMXAA...
  13. doi request reprint The nitroimidazooxazines (PA-824 and analogs): structure-activity relationship and mechanistic studies
    William A Denny
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    Future Med Chem 2:1295-304. 2010
    ..Bioreductive drugs such as PA-824 hold the promise of shorter treatment regimens...
  14. doi request reprint Intermediates in the reduction of the antituberculosis drug PA-824, (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine, in aqueous solution
    Robert F Anderson
    Department of Chemistry, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    Org Biomol Chem 6:1973-80. 2008
    ..The unique properties of the intermediates formed on the reduction of PA-824 need to be considered as playing a possible role in its bactericidal action...
  15. ncbi request reprint Synthesis and biological activity of azido analogues of 5,6-dimethylxanthenone-4-acetic acid for use in photoaffinity labeling
    Brian D Palmer
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
    J Med Chem 50:3757-64. 2007
    ..The azido compounds 2 and 3 exhibit all the requirements for use in photoaffinity labeling of potential receptor(s) for 1...
  16. ncbi request reprint Metabolism of thalidomide in liver microsomes of mice, rabbits, and humans
    Jun Lu
    The Auckland Cancer Society Research Center, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    J Pharmacol Exp Ther 310:571-7. 2004
    ..The very low rate of in vitro and in vivo hydroxylation in humans strongly suggests that thalidomide hydroxylation is not a requirement for clinical anticancer activity...
  17. ncbi request reprint Effect of nitroreduction on the alkylating reactivity and cytotoxicity of the 2,4-dinitrobenzamide-5-aziridine CB 1954 and the corresponding nitrogen mustard SN 23862: distinct mechanisms of bioreductive activation
    Nuala A Helsby
    Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    Chem Res Toxicol 16:469-78. 2003
    ..The single-step bioactivation of 6, to amino or hydroxylamine metabolites with similar potency to 4, is a potential advantage in the use of dinitrobenzamide mustards as prodrugs for activation by nitroreductases...
  18. ncbi request reprint Uptake of the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and activation of NF-kappaB in human tumor cell lines
    See Tarn Woon
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand
    Oncol Res 13:95-101. 2002
    ..The observed activation of NF-kappaB in some lines suggests that the effects of DMXAA on tumor cells, as well as host cells, must be considered in understanding its antitumoraction...
  19. ncbi request reprint Thalidomide pharmacokinetics and metabolite formation in mice, rabbits, and multiple myeloma patients
    Francisco Chung
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
    Clin Cancer Res 10:5949-56. 2004
    ..Thalidomide has a variety of biological effects that vary considerably according to the species tested. We sought to establish whether differences in pharmacokinetics could form a basis for the species-specific effects of thalidomide...
  20. doi request reprint Formation of an N-formylkynurenine-derived fluorophore and its use for measuring indoleamine 2,3-dioxygenase 1 activity
    Petr Tomek
    Auckland Cancer Society Research Centre and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand
    Anal Bioanal Chem 405:2515-24. 2013
    ....
  21. ncbi request reprint Aziridinyldinitrobenzamides: synthesis and structure-activity relationships for activation by E. coli nitroreductase
    Nuala A Helsby
    Auckland Cancer Society Research Centre, School of Medical Sciences, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    J Med Chem 47:3295-307. 2004
    ..The results suggest there may be advantages with carefully selected analogues of CB 1954; the weaker bystander effect of its diol derivative may be an advantage in the selective cell ablation of NTR-tagged cells in normal tissues...
  22. ncbi request reprint Thalidomide metabolites in mice and patients with multiple myeloma
    Jun Lu
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand
    Clin Cancer Res 9:1680-8. 2003
    ..This research examines the profile of metabolites of thalidomide that are formed in refractory multiple myeloma patients undergoing thalidomide therapy in comparison with those that are detected in healthy mice...
  23. ncbi request reprint Potentiation of the antitumour effect of cyclophosphamide in mice by thalidomide
    Qi Ding
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
    Cancer Chemother Pharmacol 50:186-92. 2002
    ..We wished to determine whether thalidomide potentiated the effect of cyclophosphamide, a commonly used cytotoxic drug, in a murine tumour model...