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If the design principle was successful, the nitrile nitrogen atom would be able to engage the tyrosine hydroxy substituents directly by H-bonding and the energetics of the drug-target association would benefit from the entropic advantage of displacing the H2O molecule, as depicted in Fig. A cinnoline-3-carbonitrile has found application in the design of inhibitors of scytalone dehydratase, an enzyme in the plant fungal pathogen Magnaporthe grisea that catalyzes two steps in the melanin biosynthesis pathway . The amide carbonyl moiety engaged in a dual H-bonding interaction with the side chain guanidine terminus of Arg207, which is known to engage the amide carbonyl and CO2H terminus element of pantothenic acid monophosphate (Fig. 41) [202, 203, 205]. 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