Синтез и биологическая активность карбамоилированных 1,1,1,3,3,3-гексафторизопропанолов - новых специфических ингибиторов карбоксилэстеразы

A series of O-phosphorylated 1,1,1,3,3,3-hexafluoroisopropanols of the general formula RNHC(O)OCH(CF3)2 (R=СН3, n-С3Н7, tert -С4Н9, cyclo-C6H11, С6H5, С6H5-CH2, 3-Cl-C6H4, 4-Cl-C6H4, 3,4-Cl2-C6H3, naphthalen-2-yl) have been synthesized. The kinetics of interaction of the synthesized carbamates with three serine esterases - human erythrocyte acetylcholinesterase (EC 3.1.1.7), horse serum butyrylcholinesterase (EC 3.1.1.8), and porcine liver carboxyl esterase (EC 3.1.1.1) - has been studied. It is established that the synthesized сarbamates do not inhibit acetylcholinesterase, weakly inhibit butyrylcholinesterase, and produce selective inhibition of the activity of carboxyl esterase. A new selective irreversible inhibitor of carboxyl esterase, 2,2,2-trifluoromethylethyl ester of cyclohexylcarbamic acid, has been obtained, which is characterized by low acute toxicity.