Eki785

CH3 O

o

The last four compounds can be considered as active site-directed irreversible inhibitors, since they contain a 4-anilinoquinazoline structural fragment that can be recognized by the ATP site and also an electrophilic a,p-unsaturated carbonyl moiety, responsible for covalent binding to the enzyme. The conserved cysteine residue Cys-773 within the ATP binding pocket seems to be responsible for the nucleophilic attack to this Michael substrate18 (Fig. 9.9).

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