Äîêóìåíò âçÿò èç êýøà ïîèñêîâîé ìàøèíû. Àäðåñ îðèãèíàëüíîãî äîêóìåíòà : http://www.chem.msu.ru/rus/vmgu/131/45.pdf Äàòà èçìåíåíèÿ: Sat Dec 1 18:59:25 2012 Äàòà èíäåêñèðîâàíèÿ: Sun Apr 10 04:59:26 2016 Êîäèðîâêà: Ïîèñêîâûå ñëîâà: n-c

â °

`å

. . -. . 2. . 2013. . 54. 1

45

547.518


.. , .. , .. , .. , .. , . *, .. **, .. *, .. ** ( ; e-mail: olgaz@org.chem.msu.ru)
2--6-[(1H--1-)] 2--7-(1H--1-)-7-- 549. 5-(2-) .

: , , , , .

«» [1, 2] (. 1, 1 1) A549 (EC50=5­6 M) [2]. (. 2, 3), . , [3], , , (. 2). , -

. 2. ( )

. 3. 2 2 ( ).

. 1. 1 1 ( )

, [4­7]. 2, (. 3). 2 2 [8] ( 1) 3 3 ( -

* , , , ; ** .


46

. . -. . 2. . 2013. . 54. 1

DMAP [2]). 4a 4 ( 1). 13 4 ~128 .. ~179 .. , 4a () ( 1). 1 5 6.74 .., 13 ­ 149.92 .. 5. : (CH2Cl2, .) . , N- 3 ( SOCl2 Et3N), 3 DCC/DMAP, 2--N--1,2 (EEDQ). (c 2)

6 97% ( . ). 5 6 549 3-(4,5 -2)-2,5--2 H - () [9]. 5 6 (EC50>10 µM) 1 1. 2 2 . Silufol-UV254. Acros (40­60 ). 1H 13C CDCl3 «Bruker Avance 400» «Varian» 400 100 . (..) 7.28 77.0 .. CHN «Vario micro cube». - KBr «IR-200» («ThermoNicolet»). 5-(2-) (4a). 3a (0,111 ; 0,38 ), (0,060 ;
1

2


. . -. . 2. . 2013. . 54. 1

47

0,43 ) (PhO)2P(O)N3 (0,098 , 0,45 ) 1043, 1101, 1215, 1255, 1290, 1319, 1340, 1452, 1477, 10 8 80°. 152, 1543, 1610, 1726 (C=O), 2856, 2910, 2927, 3059, , 3109. . (%): (70,44), (: ­ H (7,68), N (10,19). C24H31N3O3. (%): (40­70°), 1:15). 0,108 (70,39), H (7,63), N (10,26). 4 ( 97%) 2--7-(1H--1-)-7-1 , Rf 0,68. : 1.41­1.48 (6). 3 (0,021 ; 0,071 (2H), 1.56­1.59 (2, HAd), 1.67 (4H), 1.75­1.79 ), (0,010 ; 0,085 ) EEDQ (4H, HAd), 1.85­1.87 (4H, HAd), 1.99­2.02 (4H, HAd), (0,021 ; 0,085 ) 5 CH2Cl2 2.37 (2, J=7.2 , H2CO2), 3.32 (2, J = 6.7 , 4 . H2NCO), 4.93 (1H, H2-Ad). 13: 24.50, , (: 26.10, 26.98, 27.23, 30.79, 31.79, 31.97, 34.61, 36.32, ­ (40­70°), 1:4, 37.37, 42.79 (CH2NCO), 76.90 (2-Ad), 128.27 (NCO), ­ , 1:20). 0,027 172.82 (C=O). (-1): 1256, 1421,1452, 6 ( 97%) . 1: 1.48­1.61 (4H), 1.70­ 1720 (C=O), 2277 (NCO), 2929, 3054. 6-(2-) - 1.81 (6H), 1.83 (4H), 1.89­1.95 (2H), 1.95­2.04 (4) 4 (4H, HAd), 2.40 (2H, J = 7,4 , H2CO2), 3.03 (2H, J 3 (0,150 ; 0,49 ), - = 7,3 , H2CON), 4.94 (1H, H2-Ad), 7.37­7.46 (2H, (0,074 , 0,56 ) (PhO)2P(O)N3 (0,115 ; H5,6-Ar), 7.81 (1H, J = 7.4, 1.1 , H4-Ar), 8.25 (1H, J 0,53 ). 0,142 4 (- = 7.1 , H7-Ar), 8,41 (1H, H2-Ar). . 95%) , (%): (73,12), H (7,64), N (7,18). C24H30N2O3. Rf 0.70. 1: 1.34­1.42 (2H); 1.53­1.57 (%): (73,07), H (7,66), N (7,10). (2, HAd); 1.59­1.69 (6H); 1.72­1.77 (4H, HAd), MTT- 1.82­1.85 (4H, HAd); 1.97­2.01 (4H, HAd); 2.33 (2, 549 J = 7.2 , H2CO2); 3.28 (2, J = 6.7 , H2NCO); 2-Ad -1 4.91 (1H, H ). ( ): 1264, 1420, 1448, 96 ( 3000­ 6000 200 µ DMEM 1723 (C=O), 2270 (NCO), 2900­3050 (. ). 2- -6-[(1 H - -1- 10% )] (5). - ). 24 4a (0,100 ; 0,34 ) (0,057 ; 5 6 0,48 ) 5 - 0,005­10,000 µM 3 . - 0,001­0,300 µM , (8 ). (: ­ (40­70°), MTT 5 / - 1:7). 0,12 4 ( 86%) 0,22 . 2 . 1 : 1.43­1.50 (2H), 1.52­1.55 (2, HAd), 1.69­1.75 20 µ (8H, H2+HAd), 1.80­1.83 (4H, HAd), 1.96­1.99 MTT , (4H, HAd), 2.38 (2, J=7.1 , H2CO2), 3.53 (2, 0,45 /. J = 6.9, 5.8 , H2NHCO), 4.91 (1H, H2-Ad), 6.74 100 µ . (1H, NH), 7.33­7.42 (2H, H5,6-Ar), 7.78 (1H, (, 10% J = 8.0 , H4-Ar), 7.96 (1H, J = 8.0 , H7-Ar), 8.51 0,6% ). (1H, H2-Ar). 13: 24.13, 25.97, 26.71, 26.6, 28.67, 31.53, 31.66, 34.30, 36.05, 37.09, 42.48 (CH2N- . CO), 76.54 (2-Ad), 113.43, 120.22, 123.80, 124.83, 590 131.36 (C7a-Ar), 140.49 (C2-Ar), 143.57 (C3a-Ar), 149.92 690 «EL808 Ultra Microplate Reader» (N-C=O), 173.20 (C=O). (-1): 966, 985, («Bio-Tek Instruments», ). (3.4-Fokoop-Rus/1015567) ( 12-03-00720_ 11-03-12088_-).


48 1. Zefirova O.N., Nurieva E.V., Lemcke H., Ivanov A.A., Shishov D.V., Weiss D.G., Kuznetsov S.A., Zefirov N.S. // Bioorg. Med. Chem. Lett. 2008. 18. P. 5091. 2. Zefirova O.N., Nurieva E.V., Shishov D.V., Baskin I.I., Fuchs F., Lemcke H., Weiss D.G., SchrÆder F., Zefirov N.S., Kuznetsov S.A. // Bioorg. Med. Chem. 2011. 19. P. 5529. 3. Nguyen T.L., McGrath C., Hermone A.R., Burnett J.C., Zaharevitz D.W., Day B.W., Wipf P., Hamel E., Gussio R. // J. Med. Chem. 2005. 48. P. 6107. 4. . . , . . , . . , . ., . ., . . // . 2003. 73. C. 1367. (. Pilyugin V.S., Mikhailyuk A.N.,

. . -. . 2. . 2013. . 54. 1

5. 6. 7. 8.

Kosareva V.M., Valitov R.B., Kiseleva G.V., Kuznetsova S.L. // Russ. J. Gen. Chem. 2003. 73. P. 1293). Hernandez-Luis F., Hernandez-Campos ., Yepez-Mulia L., Cedillo R., Castillo R. // Bioorg. Med. Chem. Lett. 2001. 11. P. 1359. Chassaing C., Berger M., Heckeroth A., Ilg T., Jaeger M., Kern C., Schmid, K., Uphoff M. // J. Med. Chem. 2008. 51. P. 1111. Ross S. T., Kruse L. I., Kingsbury W. D., Erhard K. F., Harrsch P. B. // Eur. J. Med. Chem. 1989. 24. P. 363. Cremlyn R. J. W. // Aust. J. Chem. 1973. 26. P. 1591.
13.09.12

9. Mosmann T. // J. Immunol. Methods. 1983. 65. P. 55.

SYNTHESIS AND BIOTESTS OF BENZIMIDAZOLE CONJUGATE WITH ADAMANTANE
E.V. Nurieva, A.A. Beloglazkyna, D.V. Shishov, V.V. Gogol, Y.S. Glazkova, B. Wobith, N.S. Zefirov, S.A. Kuznetsov, O.N. Zefirova (Division of rganic hemistry)
The synthesis of 2-adamantyl-6-[(1 H - b e n z i m i d a z o l e - 1 - y l c a r b o n y l ) a m i n o ] h e x a n o a t e a n d 2-adamantyl-7-(benzimidazole-1-yl)-7-oxo-heptanoate and the results of their testing for cytotoxicity against human lung carcinoma cells A549 are presented in the paper. The impossibility of 5-(2-adamantyloxycarbonyl)pentylisocyanate addition to nocodazole under various conditions is demonstrated.

Key words: benzimidazole, colchicine, nocodazole, tubulin, cytotoxicity.
: ­ . . , . . (E.Selunina@org.chem.msu.ru); ­ (anastas-beloglaz@mail.ru); ­ (shishov_d@mail.ru); ­ (Vl. gogol@gmail.com); ­ (janglaz@bk.ru); ­ , , (birgit.wobith@uni-rostock.de); ­ . , , . . , . (zefirov@org.chem.msu.ru); ­ , , , . . (sergei.kuznetsov@uni-rostock.de); ­ , . . . , . . (olgaz@org.chem.msu.ru).