As both carbamoylation and decarbamoylation are dependent on both steric and electronic factors, two other interesting analogues were prepared: with methoxy (21) and dimethylamino (22) substituents on the carbamate nitrogen (Table ). The electron-withdrawing character of these substituents should increase both de-and carbamoylation rates. Indeed, when we tried to ascertain the rate constants through k obs measurements, fast reactivation precluded the separation of the carbamoylation and decarbamoylation phases. Therefore, these two compounds are better described as slow substrates. To better understand the steric factors that affect the covalent mechanism of binding, we also tested the fragment-sized synthesis intermediates 6a, 7a, 12a and 14a (Table , Figure ). The fragments displayed non-negligible reversible binding affinities, as seen in 12a and 14a. This latter is especially interesting as it lacks the pseudo-irreversible inhibition character of the fullsized inhibitor 14, which shows that the rest of the molecule that directs the warhead into an appropriate position using reversible interactions can be an equally important factor that governs the activity of covalent inhibitors. hAChE RA at 100 µM after 30 min preincubation