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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.

81 The use of anticholinesterase compounds in medi cine, veterinary practice and agricultural chemistry is based on their common mechanism of action, which is determined by the inhibition of acetylcholinesterase (EC 3.1.1.7, AChE) [1]. Many cholinesterase inhibi tors, in addition to AChE, interact with other serine esterases, that can lead to both toxic and therapeutic effects [2]. Toxic and therapeutic effects resulting from the inhibition by organophosphorus compounds (OPCs) of four serine esterases—acetylcholinest erase, neuropathy target esterase (EC 3.1.1.5, NTE), butyrylcholinesterase (EC 3.1.1.7, BChE), and car boxylesterase (EC 3.1.1.1, CaE)—are shown in Scheme 1, where the effects that determine the toxic action of OPCs are shown in italic.

The antihypoxic and anticonvulsant activity of eight new amidophosphoryl derivatives of crown ethers was investigated. It was found that some of them exhibit pronounced antihypoxic activity. The results of an x-ray structural and IR spectroscopic study of dibenzo-N-phenylphosphonyl-14-crown-5 (a=9.818,b=16.062,c=15.925 A; γ=124.90°;V=2072 A3;M=417.2;d=1.33 g/cm3 forZ=4, 1955 independent reflections [I>3σ(I)] in a DAR-UM inCuKα radiation,P21/b space group,R=5.2%) and dibenzo-N-adamantylphosphonyl-14-crown-5 compounds (a=11.077,b=15.936,c=16.771 A; γ=56.05°;V=2456 A3;M=486.3;d=1.31 g/cm3 forZ=4, 2164 independent reflections [I>3σ(I)] in a DAR-UM inCuKα radiation,P21/b space group,R=5.1%) are reported. Some details of the structure of the dibenzo-N-phenylphosphonyl-14-crown-5-complex with calcium thiocyanate and water are discussed; a polyhedron with a coordination number of six was found for the first time for calcium complexes with macrocyclic ligands. The combined examination of the results of the biological, x-ray structural, and IR spectroscopic study of macrocyclic, 14-member ligands suggested that the nature of the substituents at phosphorus affect the conformational state of the macrocycle, which remains unchanged in complexation in the investigated conditions.