N.P. Rai et al. / European Journal of Medicinal Chemistry 45 (2010) 2677e2682
2681
(m, 4H), 7.55e7.57 (m, 1H), 7.80e7.83 (m, 2H), 7.90e7.95 (m, 1H),
8.08e8.09 (m, 1H); 13C NMR (CDCl3):
62.04, 114.90, 117.18, 117.40,
methanones (3aei) are recorded inTable 2. The values reported in the
table are the average of three experiments.
d
121.95, 122.13, 123.39, 123.43, 127.48, 127.56, 128.04, 128.47,
129.78, 130.05, 131.42, 131.65, 133.97, 153.62, 158.73, 161.26, 166.80,
174.24, 194.05; LC-MS: m/z ¼ 443.0 (Mþ); Anal. calcd for
C22H13N2O3Cl2F: C, 59.61; H, 2.96; N, 6.32. Found C, 59.39; H, 3.10;
N, 6.23.
6.2. Determination of minimum inhibitory concentration
The determination of minimum inhibitory concentration [28,29]
was done with same isolates of organisms and the MIC was defined
as the lowest concentration of the antibiotic or test sample allowing no
visible growth. The results of {5-chloro-2-[(3-substitutedphenyl-1,2,4-
oxadiazol-5-yl)-methoxy]-phenyl}-(phenyl)-methanones (3aei) are
recorded in Table 2.
5.3.7. {5-Chloro-2-[(3-(4-isopropylphenyl)-1,2,4-oxadiazol-5-yl)-
methoxy]-phenyl}-(phenyl)-methanone (3g)
IR (cmꢀ1): 3062 (ArCeH), 2960 (CeH), 1651 (C]O), 1593, 1479,
1449 (C]C), 1261 (CeOeC), 758 (CeCl); 1H NMR (CDCl3)
d ppm:
1.26e1.30 (d, 6H, 2ꢃ CH3), 2.95e2.97 (q, J ¼ 6.84 Mz, 1H), 5.25 (s,
2H, OCH2), 7.04e7.07 (m, 1H), 7.33e7.35 (d, J ¼ 8.16 Hz, 2H),
7.41e7.47 (m, 4H), 7.53e7.56 (m, 1H), 7.81e7.84 (m, 2H), 7.94e7.97
Acknowledgements
The authors are grateful to Dr. Goutham Das, President, Syngene
International Ltd., Biocon group of companies, Bangalore for giving
permission to carry out a part of the research work at their labo-
ratory and Dr. Gert Kruger, Professor, School of Chemistry, Univer-
sity of KwaZulu-Natal, Durban, South Africa for his encouragement,
support and correction of the final manuscript.
(m, 2H); 13C NMR (CDCl3):
d 23.76, 34.20, 61.96, 114.78, 123.63,
127.04, 127.54, 127.83, 128.45, 129.75, 129.79, 131.32, 131.61, 133.49,
137.00, 152.75, 153.70, 168.42, 173.62, 194.19; LC-MS: m/z ¼ 433.2
(Mþ); Anal. calcd for C25H21N2O3Cl: C, 69.36; H, 4.89; N, 6.47.
Found: C, 69.25; H, 4.95; N, 6.33.
5.3.8. {5-Chloro-2-[(3-(4-fluoro-3-methylphenyl)-1,2,4-oxadiazol-
5-yl)-methoxy]-phenyl}-(phenyl)-methanone (3h)
Appendix. Supplementary material
IR (cmꢀ1): 3050 (ArCeH), 2932 (CeH), 1655 (C]O), 1616, 1483,
Supplementary material associated with this article can be
1450 (C]C), 1259 (CeOeC), 750 (CeCl); 1H NMR (CDCl3)
d ppm:
2.33 (s, 3H, CH3), 5.25 (s, 2H, OCH2), 7.04e7.13 (m, 2H), 7.41e7.46
(m, 4H), 7.53e7.56 (m, 1H), 7.80e7.89 (m, 4H); 13C NMR (CDCl3):
References
d
14.51, 62.01, 114.86, 115.59, 115.82, 121.94, 121.97, 125.76, 125.94,
126.91, 127.00, 127.89, 128.45, 129.77, 130.81, 130.87, 131.34, 131.63,
133.49,136.99,153.70, 162.03, 164.53, 167.76,173.82, 194.10; LC-MS:
m/z ¼ 423.0 (Mþ); Anal. calcd for C23H16N2O3ClF: C, 65.33; H, 3.81;
N, 6.63. Found C, 65.21; H, 3.94; N, 6.55.
[1] K. Luthman, S. Borg, U. Hacksell, Synthesis and use of pseudopeptides derived
from 1, 2,4-oxadiazole, 1, 3,4-oxadiazole and 1, 2,4-triazole-based dipeptido-
mimetics. Methods Mol. Med 23 (1999) 1e23.
[2] B.S. Orlek, F.E. Blaney, F. Brown, M.S.G. Clark, M.S. Hadley, J. Hatcher, G.J. Riley,
H.E. Rosenberg, H.J. Wadsworth, P. Wyman, J. Med. Chem. 34 (1991)
2726e2735.
[3] C.B. Vu, E.G. Corpuz, T.J. Merry, S.G. Pradeepan, C. Bartlett, R.S. Bohacek, M.
C. Botfield, C.J. Eyermann, B.A. Lynch, I.A. MacNeil, M.K. Ram, M.R. Van
Schravendijk, S. Violette, T.K. Sawyer, J. Med. Chem. 42 (1999) 4088e4098.
[4] D.N. Nicolaides, K.C. Fylaktakidou, K.E. Litinas, D. Hadjipavlou-Litina, Eur. J.
Med. Chem. 33 (1998) 715e724.
5.3.9. {5-Chloro-2-[(3-(4-fluoro-3-methoxyphenyl)-1,2,4-
oxadiazol-5-yl)-methoxy]-phenyl}-(phenyl)-methanone (3i)
IR (cmꢀ1): 3075 (ArCeH), 2970 (CeH), 1647 (C]O), 1612, 1495,
1444 (C]C), 1259 (CeOeC), 740 (CeCl); 1H NMR (CDCl3)
d ppm:
[5] J.W. Clitherow, P. Beswick, W.J. Irving, D.I.C. Scopes, J.C. Barnes, J. Clapham,
3.95 (s, OCH3), 5.25 (s, OCH2), 7.04e7.07 (d, J ¼ 8.61 Hz, 1H),
J.D. Brown, D.J. Evans, A.G. Hayes, Bioorg. Med. Chem. Lett.
6 (1996)
7.13e7.19 (m, 1H), 7.41e7.46 (m, 4H), 7.53e7.64 (m, 3H), 7.79e7.82
833e838.
(m, 2H); 13C NMR (CDCl3):
d 56.24, 62.00, 112.13, 112.17, 114.89,
[6] A. Chimirri, S. Grasso, A.M. Montforte, A. Rao, M. Zappala, Farmaco 51 (1996)
125e129.
[7] J. Matsumoto, T. Takahashi, M. Agata, H. Toyofuku, N. Sasada, Jpn. J. Pharmacol.
65 (1994) 51e57.
[8] H.J. Lankau, K. Unverferth, C. Grunwald, H. Hartenhauer, K. Heinecke, K. Bernoster,
R. Dost, U. Egerland, C. Rundfeldt, Eur. J. Med. Chem. 42 (2007) 873e879.
[9] T. Sakamoto, M.D. Cullen, T.L. Hartman, K.M. Watson, R.W. Buckheit,
C. Pannecouque, E. De Clercq, M. Cushman, J. Med. Chem. 50 (2007) 3314e3321.
[10] L.B. Clapp, Adv. Heterocycl. Chem. 20 (1976) 65e116.
[11] P.G. Wyatt, R.C. Bethell, N. Cammack, D. Charon, N. Dodic, B. Dumaitre, D.
N. Evans, D.V.S. Green, P.L. Hopewell, D.C. Humber, R.B. Lamont, D.C. Orr, S.
J. Plested, D.M. Ryan, S.L. Sollis, R. Storer, G.G. Weingarten, J. Med. Chem. 38
(1995) 1657e1665.
116.34, 116.59, 120.55, 120.65, 122.46, 122.51, 127.86, 128.37, 129.67,
131.33, 131.56, 133.41, 136.92, 147.95, 148.10, 152.66, 153.62, 156.00,
167.65, 167.67, 173.87, 193.98; LC-MS: m/z ¼ 439.0 (Mþ); Anal. calcd
for C23H16N2O4ClF: C, 62.95; H, 3.67; N, 6.38. Found: C, 62.81; H,
3.76; N, 6.21.
6. Antibacterial activity
6.1. Antibacterial activity (determination of zone of inhibition)
[12] L. Revesz, E. Blum, F.E. Di Padova, T. Buhl, R. Feifel, H. Gram, P. Hiestand,
U. Manning, G. Rucklin, Bioorg. Med. Chem. Lett. 14 (2004) 3601e3605.
[13] A. Palomer, J. Pascual, M. Cabre, L. Borras, G. Gonzalez, M. Aparici,
A. Carabaza, F. Cabre, M.L. Garcia, D. Mauleon, Bioorg. Med. Chem. Lett. 12
(2002) 533e537.
The antibacterial activity [26,27] of the test samples (3aei) was
determined by agar cup plate method using four organisms such as B.
subtilis(NCIM,2063;ATCC6633), S.aureus(NCIM,2079;ATCC6538P),
E. coli(NCIM,2065;ATCC 8739)andK. pneumoniae(NCIM,2957;ATCC
11298) (organisms are recultured) and a standard drug, Ampicillin.
This method was based on diffusion of antibacterial component from
reservoirboretothe surroundinginoculatednutrientagarmedium so
that the growth of microorganisms was inhibited as circular zone
[14] R. Vidya, M.-J. Eggen, G.I. Georg, R.H. Himes, Bioorg. Med. Chem. Lett. 13 (2003)
757e760.
[15] F. Karrer, H. Meier, A. Pasual, J. Fluorine Chem. 103 (2000) 81e84.
[16] S.Y. Sheu, H.J. Tsai, H.C. Chiang, Anticancer Res. 19 (1999) 1131e1135.
[17] R. Martin, Org. Prep. Proced. Int. 24 (1992) 369e435.
[18] D.T. Burns, N. Tungkananuruk, S. Thuwasin, Anal. Chim. Acta 419 (2000) 41e44.
[19] A.M. Kadry, C.S. Okereke, M.S. Abdel-Rahman, M.A. Friedman, R.A. Davis, J.
Appl. Toxicol. 15 (1995) 97e102.
around the bore. The concentration of test compounds was 100 mg/
[20] L.S. White, J. Membr. Sci. 205 (2002) 191e202.
[21] H.Q. Ahmad, Heterocycles 26 (1987) 163e173.
mL. It was prepared in 20% water in dimethyl sulfoxide (DMSO). The
test samples and standard drugs were placed in a bore made in pet-
ridishes which contained different organisms and incubated at 37 ꢂC
for 24 h. The zone of inhibition around the bore was measured after
24 h. The antibacterial activity data of {5-chloro-2-[(3-substitut-
edphenyl-1,2,4-oxadiazol-5-yl)-methoxy]-phenyl}-(phenyl)-
[22] D.M. Cottrell, J. Capers, M.M. Salem, K. DeLuca-Fradley, S.L. Croft, K.
A. Werbovetz, Bioorg. Med. Chem. 12 (2004) 2815e2824.
[23] E. Elzein, P. Ibrahim, D.O. Koltun, K. Rehder, K.D. Shenk, T.A. Marquart, B. Jiang,
X. Li, R. Natero, Y. Li, M. Nguyen, S. Kerwar, N. Chu, D. Soohoo, J. Hao, V.
Y. Maydanik, D.A. Lustig, D. Zeng, K. Leung, J.A. Zablocki, Bioorg. Med. Chem.
Lett. 14 (2004) 6017e6021.