TRREVERRIBLE
Alnrch 1969
EKZYME INHIBTTORS. CXLVTT
acid chloride’ in DJIF. The phenylureas (25) were made by condensation of 23 with the appropriate 0phenyl S-(fluorosulfonylphenyl)carbamate,8 0-(p-niTABLEI I K H I B I T I OOF N ~XANTHINE OXIDASE^
BY
215
trophenyl) carbamate, or m-fluorosulfonylphenyl isocyanate in DMSO or DAIF. The requisite amines (23) were made from 17 (Scheme I). Reaction of 17 with hexamethylenetetramine followed by acid hydrolysis by the Delepirie synthesis gave 18 which was converted to 19 with acetic anhydride. Catalytic reduction to 20 followed by condensation with 2amino-A-rhloro-.i-phenyla~o-&pyrimidinol~~’~ afforded SCHEME I
NH, I
NO, I
~(CHANHCOR R 160,’ p M I O(CHz)nR 2 Ce&SOzF-m 0.53 17, R = Br 6 2 CsH4SOzF-p 0.69 7 2 C6H3-4-hte-3-SoZF 18, R = NHZ 0.49 19, R = NHAc 8 2 NHCsH4SOzF-m 0.18 9 2 PL’HC~H~SOZF-p 0.33 10 2 NHC6H3-2-Cl-5-SOzF 0.092 11 2 N HCeH3-4-Me3-SO2F 0.12 12 2 NHC6H3-2-hIeO-5-S02F 0.067 13 3 CsH4SOtF-m 0.63 14 3 CsH4SOzF-p 1.0 15 3 NHCsH4S02F-m 0.40 16 3 NHCsHBOzF-p 0.67 a The technical assistance of Julie Leseman and Maureen Baker with these assays is acknowledged. Xanthine oxidase was a commercial preparation from bovine milk that was assayed with 8.1 pfif hypoxanthine and 0 2 in 0.05 M Tris buffer (pH 7.4) containing 10Fo DMSO as previously described.bb Assays for irreversible inhibition were performed by either the uric acid assay or the 2,6-dichlorophenolindophenol assay or both2; the indophenol assay was utilized when 1 5 0 was
