The 5-nitrofuran-2-ylmethylidene group as a potential bioreductively activated prodrug system for diol-containing drugs.
Acid-catalysed condensation of 5-nitrofuran-2-carboxaldehyde with 1-phenylethane-1,2-diol and with 2,2-dimethyl-1-phenylproane-1,3-diol in boiling benzene gave the expected cyclic nitrofuranyl acetals. Biomimetic reduction of these acetals with sodium borohydride in the presence of palladium triggered release of the parent diols. Thus these nitrofuran acetals may have potential for applications as prodrugs for selective release of diol-containing drugs in hypoxic solid tumours.
Department of Pharmacy & Pharmacology, University of Bath, UK.
N P
NP
Mahmud
S W
SW
Garrett
M D
MD
Threadgill
D000080:Acetals / Q000737:chemistry*; D000970:Antineoplastic Agents; D001554:Benzene / Q000737:chemistry; D001894:Borohydrides / Q000737:chemistry; D015687:Cell Hypoxia; D003500:Cyclization; D004146:Dioxanes / Q000138:chemical synthesis* / Q000737:chemistry; D004148:Dioxolanes / Q000138:chemical synthesis* / Q000737:chemistry; D005026:Ethylene Glycols / Q000737:chemistry; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D009581:Nitrofurans / Q000138:chemical synthesis* / Q000737:chemistry*; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry; D011355:Prodrugs / Q000737:chemistry
C114800:2-(5-nitrofuran-2-yl)-4-phenyl-1,3-dioxolane; C114801:5,5-dimethyl-2-(5-nitrofuran-2-yl)-4-phenyl-1,3-dioxane; D000080:Acetals; D000970:Antineoplastic Agents; D001894:Borohydrides; D004146:Dioxanes; D004148:Dioxolanes; D005026:Ethylene Glycols; D009581:Nitrofurans; D011355:Prodrugs; C031474:styrene glycol; D010165:Palladium; C025364:sodium borohydride; D001554:Benzene