Synthesis and biological activity of O-carbamoylated 1,1,1,3,3,3-hexafluoroisopropanols as new specific inhibitors of carboxylesterase

A series of O-carbamoylated 1,1,1,3,3,3-hexafluoroisopropanols of general formula RNHC(O)OCH(CF3)2, where R = CH3, n-C3H7, tert-C4H9, cyclo-C6H11, C6H5–CH2, C6H5, 4-Cl-C6H4, 3-Cl-C6H4, 3,4-Cl2-C6H3, and naphthylen-2-yl were synthesized. The reaction kinetics of the synthesized carbamates with human erythrocyte acetylcholinesterase (EC 3.1.1.7), horse serum butyrylcholinesterase (EC 3.1.1.8), and porcine liver carboxylesterase (EC 3.1.1.1) were studied. It was shown that the synthesized carbamates did not inhibit acetylcholinesterase, inhibited weakly butyrylcholinesterase, and inhibited selectively the activity of carboxylesterase. A new selective irreversible inhibitor of carboxylesterase, 2,2,2-trifluoro-1-trifluoromethylethyl cyclohexylcarbamate, which had low acute toxicity, was obtained.