1476
KONDRATYUK et al.
Diethyl 2-aryl-5-piperidino-1,3-oxazol-4-ylphos-
taken as 100%. Measurements processing and plotting
were performed using an Origin 7.0 and 8.0 software
(OriginLab). An experimental error did not exceed
10% relative to the measured value.
phonates XIa, XIb were obtained by the method
described in [5].
Monoethyl esters of 2-aryl-5-piperidino-1,3-oxa-
zol-4-ylphosphonic acid (XIIa, XIIb). To a solution
of 0.01 mol of compound XI in 10 ml of ethanol at 20–
25°C was added a solution of 0.06 mol of NaOH in
20 ml of ethanol. The mixture was kept for 5 h. The
solvent was removed in a vacuum. The residue was
dissolved in 10 ml of water and cautiously acidified
with dilute (1:5) hydrochloric acid at 5–10°C. The
precipitate was filtered off, and the product was
purified by the recrystalization from a suitable solvent.
REFERENCES
1. Protopopova, G.V., Dzyuban, A.D., Nesterenko, N.I.,
Reidalova, L.I., Drach, B.S., Sviridov, E.P., and Shatur-
skii, Ya.P., Author’s Certificate no. 488527, 1974,
С. А., 1979, vol. 91, 205664v.
2. Brovarets, V.S., Sharykina, N.I., Kudryavtseva, I.G.,
Ovrutskii, V.M., Stepko, O.P., and Drach, B.S., Ukraine
Patent no. 17144А, 1997.
3. Lobanov, O.P. and Drach, B.S., Zh. Obshch. Khim.,
1982, vol. 52, no. 5, p. 1122.
The treatment of compounds XII with thionyl
chloride in benzene under cooling led to the tarring of
the reaction mixture, and the target products could not
be identified.
4. Drach, B.S., Sviridov, E.P., Kisilenko, A.A., and
Kirsanov, A.V., Zh. Org. Khim., 1973, vol. 9, no. 9,
p. 1818.
5. Drach, B.S., Sviridov, E.P., and Shaturskii, Ya.P Zh.
Obshch. Khim., 1974, vol. 44, no. 8, p. 1712.
6. Drach, B.S. and Mis’kevich, G.N., Zh. Org. Khim.,
1978, vol. 13, no. 7, p. 1398.
Furin activity determination. An aliquot of furin
corresponding to the cleavage of 250–300 pmol/h of 7-
amino-4-methylcoumarin from the substrate was
incubated with Boc-Arg-Val-Arg-Arg-AMC (final
concentration 100 mmol l–1) in a buffer at pH 7.2
(100 mmol of Hepes, 1 mmol of CaCl2, 0.5% Triton
X-100, and 1 mmol of β-mercaptoethanol) for 1 h at
37°C in 150 ml of sample. Amount of the released
7-amino-4-methylcoumarin was measured on a Signe-
4M (Latvia) spectrofluorimeter (excitation 380 nm,
emission 460 nm).
7. Mirskova, A.N., Zorina, E.F., and Atavin, A.S., Zh.
Org. Khim., 1972, vol. 8, no. 6, p. 1150.
8. Drach, B.S. and Sviridov, E.P., Zh. Org. Khim., 1973,
vol. 9, no. 4, p. 680.
9. Röhr, G., Schnell, M., and Köcritz, A., Synthesis, 1992,
no. 10, p. 1031.
10. Weygand, F., Steglich W., Lengyel, J., Fraunberger, F.,
Maier-Hofer, A., and Oettmeir, W., Chem. Ber., 1966,
vol. 99, p. 1944.
11. Novikova, Z.S., Skorobogatov, S.Ya., and Lutsen-
The study of the ability of the compounds to inhibit
furin was performed in the same buffer at pH 7.2. An
aliquot of the enzyme was kept with 10 ml of the test
compound in DMSO solution (initial concentration
2.10 mol l–1) for 30 min at 20–25°C. The substrate was
then added to a final concentration of 100 μmol l–1, and
the mixture was kept for 1 h (final concentration of the
tested compounds in the incubation medium 667 μmol l–1).
The substrate cleavage was stopped by adding
fluorogenic EDTA solution. The amount of released
AMC was determined as described above. The inhibit-
tion efficiency was calculated by the formula (F0 – F)/
F0, where F is the fluorescence in the presence of the
sample, F0 is the fluorescence in the absence of the test
compound. At the same time furin activity determined
in the buffer in the absence of the test compounds was
ko, I.F., Zh. Obsch. Khim., 1976, vol. 46, no. 10, p. 2213.
12. Böhme, H. and Meyer-Dulheuer, K.-H., Lieb. Ann.,
1965, vol. 688, p. 76.
13. Shevchenko, M.V. and Kukhar’, V.P., Zh. Obshch.
Khim., 1984, vol. 54, no. 7, p. 1499.
14. Anderson, G.W., Jack Blodinger, R.W., Young, R.W.,
and Welcher, A.D., J. Am. Chem. Soc., 1952, no. 21,
p. 5304.
15. Nakayama, K., Biochem J., 1997, vol. 327, no. 3,
p. 625.
16. Bergeron, F., Leduc, R., and Day, R., J. Mol. Endocrin.,
2000, vol. 24, no. 1, p. 1.
17. Thomas, G., Nat. Rev. Mol. Cell. Biol., 2002, vol. 3,
no. 10, p. 753.
18. Kibirev, V.K., Osadchuk, T.V., and Radavskii, Yu.L.,
Ukr. Biokhim. Zh., 2007, vol. 79, no. 6, p. 5.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 7 2011
Kondratyuk
