Journal of Medicinal Chemistry
Brief Article
reactions were initiated by the addition of CuOOH (125 μM). After
30 min, the reactions were stopped by snap freezing. Control
incubations included (i) 15, CYP2W1 but no CuOOH, and (ii) 15,
CuOOH but no CYP2W1.
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ASSOCIATED CONTENT
* Supporting Information
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S
Experimental details of synthetic methods used to prepare
target compounds and metabolism data associated with
evaluation of bioprecursor 29. This material is available free
AUTHOR INFORMATION
Corresponding Author
*Phone: +44 (0)1274 236482. Fax: +44 (0)1274 233234. E-
■
Present Address
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∥For N.I.: Clinical Trials Service Unit (CTSU), University of
Oxford, UK.
Author Contributions
#H.M.S. and S.T. contributed equally to this work.
Notes
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Smith, E.; Anderson, R. F.; Denny, W. A.; Wilson, W. R.; Pruijn, F. B.
Hypoxia-activated prodrugs: substituent effects on the properties of
nitro seco-1,2,9,9a-tetrahydrocyclopropa[c]-benz[e]indol-4-one (nitro-
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We thank the EPSRC NMSSC for HRMS data. This work was
supported by the EPSRC (HMS) and YCR (grant B207 to
K.P., Programme Grant to L.H.P.) and The Swedish Cancer
Society (MIS). Recombinant CYP2W1 was a kind gift from Dr.
Masaya Tachibana (Karolinska Institute).
ABBREVIATIONS USED
■
CBI, chloromethylbenzoindoline; CHO, Chinese hamster
ovary; CPI, chloromethylpyrroloindoline; CYP, cytochrome
P450; EDCI, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide;
HEK, human embryonic kidney; TTMSS, tris(trimethylsilyl)-
silane
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