IRREVERSIBLE ENZYME INHIBITORS .125. ACTIVE-SITE-DIRECTED IRREVERSIBLE INHIBITORS OF XANTHINE OXIDASE DERIVED FROM ARYLPURINES AND PYRAZOLO[3,4-D]PYRIMIDINES BEARING A TERMINAL SULFONYL FLUORIDE

4-Hydroxy-6-phenylpyrazolo[3,4-d]pyrimidines with m-fluorosulfonylbenzamido (14(or -p-fluorosulfonylbenzamido (16) groups on the meta position are active-site-direeted irreversible inhibitors of xanthine oxidase; in contrast, the m-fluorosulfonylbenzamido substituent on the para position (17) does not give an irreversible inhibitor. Replacement of the 4-hydroxy group of 14 or 16 by amino (11, 12) gives no loss of reversible inhibition, but irreversible inhibition is eradicated. Similarly, these fluorosulfonylbenzamido groups on the meta or para position of 8-phenyladenine (8-10) afford better reversible inhibitors, but irreversible inhibition is again lost. The seven types of active-site-directed irreversible inhibitors of xanthine oxidase found to date are compared in efficiency. © 1968, American Chemical Society. All rights reserved.