A new spacer group derived from arylmalonaldehydes for glucuronylated prodrugs

Bioorg Med Chem Lett. 1998 Sep 22;8(18):2545-8. doi: 10.1016/s0960-894x(98)00454-5.

Abstract

A new glucuronylated prodrug of doxorubicin, potentially useful for ADEPT or PMT cancer chemotherapy, has been prepared from 4-methyl phenyl malonaldehyde. The enol ether spacer, linked via a carbamate to the 3'-amino group of doxorubicin is rapidly cleaved after beta-glucuronidase (E coli) catalyzed hydrolysis at pH 7.2 and 37 degrees C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / chemical synthesis*
  • Antibiotics, Antineoplastic / chemistry
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / chemistry
  • Glucuronates / chemistry*
  • Glucuronidase / metabolism
  • Models, Chemical
  • Molecular Structure
  • Prodrugs / chemical synthesis*
  • Prodrugs / chemistry

Substances

  • Antibiotics, Antineoplastic
  • Glucuronates
  • N-(4-glucuronyl-3-nitrobenzyloxycarbonyl)doxorubicin
  • Prodrugs
  • Doxorubicin
  • Glucuronidase