A new spacer group derived from arylmalonaldehydes for glucuronylated prodrugs.
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.
Papot
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Laboratoire de Chimie 12, Université de Poitiers et CNRS, Poitiers, France.
Combaud
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Gesson
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JP
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000737:chemistry; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry; D005965:Glucuronates / Q000737:chemistry*; D005966:Glucuronidase / Q000378:metabolism; D008956:Models, Chemical; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry
D000903:Antibiotics, Antineoplastic; D005965:Glucuronates; C114198:N-(4-glucuronyl-3-nitrobenzyloxycarbonyl)doxorubicin; D011355:Prodrugs; D004317:Doxorubicin; D005966:Glucuronidase