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P. Shukla et al. / Bioorg. Med. Chem. Lett. 21 (2011) 3475–3478
2-[4-{3-(4-Chloro-phenyl)-acryloyl}-phenoxy]-2-methyl- propionic acid ethyl
ester (4b): Yield: 77%; mp: 112–114 °C; MS (ESI): 373 (M+1), IR (KBr): 3424,
3021, 2359, 1604; 1H NMR (300 MHz, CDCl3): d 7.97 (d, J = 8.85 Hz, 2H, 20,60-H),
7.74 (d, J = 15.63 Hz, 1H, b-H), 7.56 (d, J = 8.49 Hz, 2H, 2,6-H), 7.49 (d,
the solvent was removed from filtrate and the products 4 and 8
were purified by column chromatography.14
J = 15.63 Hz, 1H,
a-H), 7.38 (d, J = 8.46 Hz, 2H, 3,5-H), 6.88 (d, J = 8.85 Hz, 2H,
Acknowledgments
30,50-H), 4.23 (q, 2H, OCH2), 1.67 (s, 6H, C-CH3), 1.23 (t, 3H, CH3).
2-[4-{3-(4-Nitro-phenyl)-acryloyl}-phenoxy]-2-methyl-propionic acid ethyl
ester (4c): Yield: 92%; mp: 126–128 °C; MS (ESI): 384 (M+1); IR (KBr): 3020,
2358, 1732, 1601; 1H NMR (300 MHz, CDCl3): d 8.28 (d, J = 8.82 Hz, 2H, 3,5-H),
7.99 (d, J = 8.91 Hz, 2H, 20,60-H), 7.80 (d, J = 15.66 Hz, 1H, b-H), 7.78 (d,
Authors are thankful to the Director CDRI for financial support,
Laboratory Animal Division for the animals and Sophisticated
Analytical Instrumentation Facility (SAIF) group for spectral data.
P.S. and S.P.S. are grateful to UGC and CSIR, New Delhi for awarding
Senior Research fellowship.
J = 8.7 Hz, 2H, 2,6-H), 7.63 (d, J = 15.69 Hz, 1H,
a-H), 6.90 (d, J = 8.85 Hz, 2H,
30,50-H), 4.25 (q, 2H, OCH2), 1.68 (s, 6H, C-CH3), 1.23 (t, 3H, CH3).
2-[4-{3-(4-Methyl-phenyl)-acryloyl}-phenoxy]-2-methyl- propionic acid ethyl
ester (4d): Yield: 81%; mp: 83–85 °C; MS (ESI): 353 (M+1); IR (KBr): 3021,
1
2360, 1600; H NMR(300 MHz, CDCl3): d 7.90 (d, J = 8.85 Hz, 2H, 20,60-H), 7.71
References and notes
(d, J = 15.63 Hz, 1H, b-H), 7.47 (d, J = 7.10 Hz, 2H, 2,6-H), 7.42 (d, J = 15.69 Hz,
1H, a
-H), 7.14 (d, J = 7.98 Hz, 2H, 3,5-H), 6.81 (d, J = 8.85 Hz, 2H, 30,50-H), 4.17
1. Mohiuddin, S. M.; Pepine, C. J.; Kelly, M. T.; Buttler, S. M.; Setze, C. M.; Sleep, D.
J.; Stolzenbach, J. C. Am. Heart J. 2009, 157, 195.
2. (a) Sharrett, A. R.; Ballantyne, C. M.; Coady, S. A.; Heiss, G.; Sorlie, P. D.;
Catellier, D.; Patsch, W. Circulation 2001, 104, 1108; (b) Sarwar, N.; Danesh, J.;
Eiriksdottir, G.; Sigurdsson, G.; Wareham, N.; Bingham, S.; Boekholdt, S. M.;
Khaw, K. T.; Gudnason, V. Circulation 2007, 115, 450.
(q, 2H, OCH2), 2.32 (s, 3H, CH3), 1.60 (s, 6H, C-CH3), 1.15 (t, 3H, CH3).
2-[4-{3-(2-Chloro-phenyl)-acryloyl}-phenoxy]-2-methyl-propionic acid ethyl
ester (4e): Yield: 56%; MS (ESI): 373 (M+1); IR (neat): 3021, 2361, 1653; 1H
NMR(300 MHz, CDCl3): d 8.08 (d, J = 15.72 Hz, 1H, b-H), 7.90 (d, J = 8.82 Hz, 2H
20,60-H), 7.65 (d, J = 6.33 Hz, 1H, 6-H), 7.41 (d, J = 15.66 Hz, 1H,
a-H), 7.36 (m,
1H, 4-H), 7.34–7.28 (m, 2H, 3, 5–H), 6.81 (d, J = 8.85, 2H, 30,50-H), 4.15 (q, 2H,
3. Abello, F.; Baracco, V.; Guardamagna, O. Nutr. Metab. Cardiovasc. Dis. 2008, 18,
35.
OCH2), 1.58 (s, 6H, C-CH3), 1.15 (t, 3H, CH3).
2-[4-{3-Benzo(1,3)dioxol-5-yl-acryloyl}-phenoxy]-2-methyl-propionic
acid
4. Leiter, L. A. Diabetes Res. Clin. Pract. 2005(68), S3 (Suppl. 2).
5. (a) Krukemyer, J. J.; Talbert, R. L. Pharmacotherapy 1987, 7, 198; (b) Hebert, P.
R.; Gaziano, J. M.; Chan, K. S.; Hennekens, C. H. J. Am. Med. Assoc. (JAMA) 1997,
278, 313.
ethyl ester (4f): Yield: 78%; mp: 98–100 °C; MS (ESI): 383 (M+1); IR (KBr):
3021, 2360, 1598; 1H NMR (300 MHz, CDCl3): d 7.89 (d, J = 8.79 Hz, 2H, 20,60-H),
7.65 (d, J = 15.36 Hz, 1H, b-H), 7.29 (d, J = 15.51 Hz, 1H, a-H), 7.20 (s, 1H, 2-H),
7.09 (m, 2H, 30, 50-H), 6.82–6.76 (m, 2H, 5,6-H), 5.96 (s, 2H, OCH2O), 4.17 (q, 2H,
OCH2), 1.60 (s, 6H, C-CH3), 1.18 (t, 3H, CH3).
6. (a) Watts, G. F.; Dimmitt, S. B. Curr. Opin. Lipidol. 1999, 10, 561; (b) Ozasa, H.;
Miyazawa, S.; Furuta, S.; Osumi, T.; Hashimoto, T. J. Biochem. 1985, 97, 1273.
7. (a) Jacob, S. S.; Jacob, S.; Williams, C.; Deeg, M. A. Diabetes Care 2005, 28, 1258;
(b) Rallidis, L. S.; Apostolou, T. S. Hellenic J. Cardiol. 2002, 43, 219.
8. Vaya, J.; Belinky, P. A.; Aviram, M. Free Radic. Biol. Med. 1997, 23, 302.
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Bioorg. Med. Chem. 2004, 12, 883; (b) Shukla, P.; Singh, A. B.; Srivastava, A. K.;
Pratap, R. Bioorg. Med. Chem. Lett. 2007, 17, 799; (c) Pratap, R.; Satyanarayana,
M.; Nath, C.; Raghubir, R.; Puri, A.; Chander, R.; Tiwari, P.; Tripathi, B. K.;
Srivastava, A. K. U.S. Patent 7,807,712 B2, 2010.
10. Zhong, B.; Li, W.; He, X.; Li, M.; Liu, H.; Chen, L. Chinese Patent, Publication no.
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Sandler, S. Eur. J. Endocrinol. 2002, 147, 543.
2-[4-{3-(2-Methoxy-phenyl)-acryloyl}-phenoxy]-2- methyl-propionic acid
ethyl ester (4g): Yield: 70%; MS (ESI): 369 (M+1); IR (neat): 3022, 2362,
1600; 1H NMR(300 MHz, CDCl3): d 7.75 (d, J = 15.66 Hz, 1H, b-H), 7.63–7.57 (m,
3H, 6, 20,60-H), 7.46 (d, J = 14.88 Hz, 1H,
a-H), 7.06–7.03 (m, 1H, 4-H), 7.37–7.30
(m, 2H, 3, 5–H), 6.92 (d, J = 8.67, 2H, 30,50-H), 4.24 (q, 2H, OCH2), 3.84 (s, 3H,
OCH3), 1.58 (s, 6H, C-CH3), 1.22 (t, 3H, CH3).
2-[4-{3-(4-Fluoro-phenyl)-acryloyl}-phenoxy]-2-methyl-propionic acid ethyl
ester (4h): Yield: 73%; mp: 110–112 °C; MS (ESI): 357 (M+1), IR (KBr): 3422,
3020, 2360, 1600; 1H NMR(300 MHz, CDCl3): d 7.98 (d, J = 8.82 Hz, 2H, 20,60-H),
7.77 (d, J = 15.66 Hz, 1H, b-H), 7.64 (d, J = 8.49 Hz, 2H, 2,6-H), 7.46 (d,
J = 15.60 Hz, 1H,
a-H), 7.09 (d, J = 9.00 Hz, 2H, 3,5-H), 6.90 (d, J = 8.82 Hz, 2H,
30,50-H), 4.23 (q, 2H, OCH2), 1.68 (s, 6H, C-CH3), 1.26 (t, 3H, CH3).
2-Methyl-2-[3-(3-oxo-3-phenyl-propenyl)-phenoxy]-propionic acid ethyl
ester (8a): Yield: 77%; MS (ESI): 339 (M+1); IR (KBr): 3420, 3021, 2362,
1
1602; H NMR (300 MHz, CDCl3): d 8.03 (d, J = 7.35 Hz, 2H, 20,60-H), 7.76 (d,
J = 15.69 Hz, 1H, b-H), 7.50 (d, J = 15.99 Hz, 1H,
a
-H), 7.61–7.50 (m, 3H, 30, 40,
50-H), 7.31–7.20 (m, 2H, 5, 6-H), 7.17 (s, 1H, 2-H), 6.90 (m, 1H, 4-H), 4.27 (q, 2H,
-OCH2), 1.65 (s, 6H, C-CH3), 1.25 (t, 3H, CH3).
14. Spectral data of the compounds: 2-[4-{3-(3, 5-Dichloro-phenyl)-acryloyl}-
phenoxy]-2-methyl-propionic acid ethyl ester (4a): Yield: 64%; mp: 94–
96 °C; MS (ESI): 407, 409 (M+, M+2), IR (KBr): 3021, 2359, 1606; 1H NMR
(200 MHz,CDCl3): d 7.97 (d, J = 8.84 Hz, 2H, 20,60-H), 7.72 (s, 1H, 4H), 7.68 (d,
2-Methyl-2-[4-(3-oxo-3-phenyl-propenyl)-phenoxy]-propionic acid ethyl
ester (8b): Yield: 45%; MS (ESI): 339 (M+1); IR (KBr): 3418, 3025, 2363,
1
1601; H NMR (300 MHz, CDCl3): d 7.94 (d, J = 7.20 Hz, 2H, 20,60-H), 7.71 (d,
J = 15.60 Hz, 1H, b-H), 7.53–7.31 (m, 6H, 30,40,50, 2, 6,
a-H), 6.87 (d, J = 8.70 Hz,
J = 15.74 Hz, 1H, b-H), 7.49 (d, J = 15.72 Hz, 1H,
a-H), 7.47 (d, J = 2.68 Hz, 2H,
2H, 3, 5-H), 4.25 (q, 2H, OCH2), 1.68 (s, 6H, C-CH3), 1.23 (t, 3H, CH3).
2,6-H), 6.89 (d, J = 8.86 Hz, 2H, 30,50-H), 4.24 (q, 2H, OCH2), 1.67 (s, 6H, C-CH3),
1.23 (t, 3H, CH3).