Analogues of azepinomycin as inhibitors of guanase.
Synthesis and biochemical screening against guanase of analogues of the naturally occurring guanase inhibitor azepinomycin (2) are reported. Compound 6-amino-5,6,7,8,-tetrahydro-4H-imidazo[4,5-e][1,4]diazepine-5,8-dione (3) was synthesized in six steps commencing with 1-benzyl-5-nitroimidazole-4-carboxylic acid (5). Compound 3 and its synthetic precursor 3-benzyl-6-(N-benzyloxycarbonyl)amino-5,6,7,8-tetrahydro-4H-imidazo[4,5- e] [1,4]diazepine-5,8-dione (12) were screened against rabbit liver guanase. Both were found to be moderate inhibitors of the enzyme with K's in the range of 10(-4) M.
Rajappan
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Department of Chemistry and Biochemistry, University of Maryland, Baltimore 21250, USA.
Hosmane
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D000818:Animals; D001381:Azepines / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006148:Guanine Deaminase / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008956:Models, Chemical; D011817:Rabbits; D013329:Structure-Activity Relationship
D001381:Azepines; D004791:Enzyme Inhibitors; C054358:azepinomycin; D006148:Guanine Deaminase