Latent alkyl isocyanates as inhibitors of aldehyde dehydrogenase in vivo.
1994
On the basis of our previous observation that N 1 -alkyl substituted chlorpropamide derivatives when administered to rats nonenzymatically eliminated n-propyl isocyanate, a known inhibitor of aldehyde dehydrogenase (AlDH), we have synthesized other latentiated n-propyl isocyanates as in vivo inhibitors of AlDH. n-Allylchlorpropamide 3 was, as expected, a potent inhibitor of hepatic AlDH in rats, as indicated by the 4-fold increase in the levels of ethanol-derived blood acetaldehyde relative to that elicited by chlorpropamide itself. Closely following in activity in decreasing order were N 3 -(n-propylcarbamoyl)uracil (7), N-(n-propylcarbamoyl)saccharin (6), and the S-(n-propylcarbamoyl) derivative (9) of benzyl mercaptan
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