Alkylating Reagents Containing Phosphoric Ester Groups for Prodrug Design

Phosphoric esters are widely used in the field of prodrugs to modulate lipophilicity/water-solubility and to improve bioavailability compared to the parent drugs.¹⁾ Dibenzyl chloromethyl phosphate (1) and di-tert-butyl chloromethyl phosphate (2) enable facile introduction of phosphoric ester groups to various nucleophiles. Moreover, 1 and 2 have protective groups with different deprotection conditions, which can be used depending on the desired synthetic route.^2,3)

Related Products

D5828

Dibenzyl Chloromethyl Phosphate

D5835

Di-tert-butyl Chloromethyl Phosphate (*This product is discontinued.)

References

• 1) Prodrugs: design and clinical applications
  • J. Rautio, H. Kumpulainen, T. Heimbach, R. Oliyai, D. Oh, T. Järvinen, J. Savolainen, Nat. Rev. Drug Discov. 2008, 7, 255.
• 2) Fluorescence Probe for Lysophospholipase C/NPP6 Activity and a Potent NPP6 Inhibitor
  • M. Kawaguchi, T. Okabe, S. Okudaira, K. Hanaoka, Y. Fujikawa, T. Terai, T. Komatsu, H. Kojima, J. Aoki, T. Nagano, J. Am. Chem. Soc. 2011, 133, 12021.
• 3) Synthesis and evaluation of prodrugs of corticotropin-releasing factor-1(CRF₁) receptor antagonist BMS-665053 leading to improved oral bioavailability
  • R. A. Hartz, V. M. Vrudhula, V. T. Ahuja, J. E. Grace, N. J. Lodge, J. J. Bronson, J. E. Macor, Bioorg. Med. Chem. Lett. 2017, 27, 1360.

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