J. Almaliti et al. / Bioorg. Med. Chem. Lett. 23 (2013) 1232–1237
1237
properties of these compounds. Na+/K+-ATPase has a significant
role in cerebral ischemia pathophysiology. Therefore, compounds
with Na+/K+-ATPase enhancing activity will be useful as agents in
the treatment of neurologic disorders such as stroke and cerebral
ischemia. Further studies are in progress to validate their efficacy
as potential lead molecules for developing therapeutic agents for
neurodegenerative diseases.
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This work was supported partly by a Grant from the National
Institutes of Health (R00AT004197) to Z.A.S. The authors thank
Dr. Kristin Kirschbaum and Nicholas Amato for X-ray crystallogra-
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Supplementary data
Supplementary data associated with this article can be found, in
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36. Compound characterization data:
Compound 12: Yellow oil, mp 70–73 °C. 1H NMR (400 MHz, CDCl3) 1.19–1.25
(m, 1H), 1.4–1.57 (m, 2H), 1.65–1.68 (m, 1H), 1.43 (s, 3H), 1.91–1.94 (m, 1H),
2.09–2.14 (m, 1H), 2.21–2.24 (m, 1H), 6.18 (s, 1H), 6.60 (m, 1H), 7.48 (m, 1H),
7.80 (s, 1H). 13C NMR (CDCl3, 100 MHz): 20.17, 21.38, 21.63, 24.97, 36.76,
45.73, 55.18, 110.03, 120.17, 125.82, 142.67, 143.89, 173.96, 208.96 ppm.
HRMS: (ESI) calcd for C14H16O2 [M+Na]+ 239.1048; found 239.1056.
Compound 13: White crystals, mp 74–80 °C. 1H NMR (400 MHz, CDCl3) 1.25–
1.31(m, 1H),1.32 (s, 1H), 1.44–1.49 (m, 1H), 1.65–1.77 (m, 5H), 1.96–2.02 (m,
1H), 2.59 (s, 1H), 6.19 (s, 1H), 6.62 (d, J = 1.2 Hz, 1H), 7.51 (m, 1H), 7.85 (s, 1H).
13C NMR (CDCl3, 100 MHz): d 19.56, 20.83, 26.18, 32.83, 33.93, 50.20, 80.98,
109.95, 120.30, 123.25, 142.85, 144.10, 172.75, 210.19 ppm. HRMS: (ESI) calcd
for C14H16O2 [M+Na]+ 255.0998; found 255.0992.
References and notes
1. Meyers, P. M.; Schumacher, H. C.; Connolly, E. S., Jr.; Heyer, E. J.; Gray, W. A.;
Higashida, R. T. Circulation 2011, 123, 2591.
2. Roger, V. L.; Go, A. S.; Lloyd-Jones, D. M.; Adams, R. J.; Berry, J. D.; Brown, T. M.;
Carnethon, M. R.; Dai, S.; de Simone, G.; Ford, E. S.; Fox, C. S.; Fullerton, H. J.;
Gillespie, C.; Greenlund, K. J.; Hailpern, S. M.; Heit, J. A.; Ho, P. M.; Howard, V. J.;
Kissela, B. M.; Kittner, S. J.; Lackland, D. T.; Lichtman, J. H.; Lisabeth, L. D.;
Makuc, D. M.; Marcus, G. M.; Marelli, A.; Matchar, D. B.; McDermott, M. M.;
Meigs, J. B.; Moy, C. S.; Mozaffarian, D.; Mussolino, M. E.; Nichol, G.; Paynter, N.
P.; Rosamond, W. D.; Sorlie, P. D.; Stafford, R. S.; Turan, T. N.; Turner, M. B.;
Wong, N. D.; Wylie-Rosett, J. Circulation 2011, 123, e18.
Compound 14: White crystals, mp 110–112 °C. 1H NMR (400 MHz, CDCl3) 1.35
(s, 3H), 1.48–1.49 (m, 2H), 1.71–1.72 (m, 3H), 1.88–2.02 (m, 3H), 3.40 (br, 1H),
6.05 (s, 1H), 6.51–6.52 (m, 1H), 7.46 (s, 1H), 7.61 (s, 1H). 13C NMR (CDCl3,
100 MHz): 20.02, 20.59, 22.72, 34.98, 36.89, 42.91, 104.80, 110.44, 115.93,
122.33, 141.46, 143.68, 157.49, 164.28 ppm. HRMS: (ESI) calcd for C14H16O2
[M+Na]+ 271.0946; found 271.0936.
3. Fisher, M.; Brott, T. G. Stroke 2003, 34, 359.
4. Malik Zafar, A.; Singh, M.; Sharma, P. L. J. Ethnopharmacol. 2011, 133, 729.
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Bioorg. Med. Chem. 2010, 18, 3133.
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Bioorg. Med. Chem. Lett. 2009, 19, 6009.
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Compound 15: White solid, mp 70–73 °C. 1H NMR (400 MHz, CDCl3) 0.96–1.04
(m, 1H), 1.13 (s, 3H), 1.22–1.25 (m, 2H), 1.42–1.47 (m, 1H), 1.59–1.67 (m, 2H),
1.98–2.04 (m, 1H), 2.38–2.46 (m, 1H), 2.74–2.81 (m, 1H), 3.46–3.51 (t,
J = 9.6 Hz, 1H), 6.29 (s, 1H), 7.26 (s, 1H), 7.39 (m, 1H). 13C NMR (CDCl3,
100 MHz): 16.51, 20.81, 23.74, 28.73, 31.39, 38.55, 38.88, 45.01, 80.37, 111.12,
122.63, 140.24, 143.03, 215.70 ppm. HRMS: (ESI) calcd for C14H16O2 [M+Na]+
257.1154; found 257.1154.
Compound 16: White crystals, mp 76–81 °C. 1H NMR (400 MHz, CDCl3) 1.24–
1.35 (m,1H),1.36 (s, 3H) 1.42–1.49 (m, 1H), 1.59–1.83 (m, 5H), 2.07–1.13
(m,1H), 2.55 (s,1H), 6.36 (s,1H), 6.56 (m, 1H), 6.90 (d, J = 3.66 Hz, 1H), 7.59 (d,
J = 1.83 Hz, 1H). 13C NMR (CDCl3, 100 MHz): d 19.28, 20.51, 25.73, 32.80, 33.73,
49.22, 80.73, 112.81, 115.51, 121.06, 145.57, 149.33, 167.45, 209.85 ppm.
HRMS: (ESI) calcd for C14H16O2 [M+Na]+ 255.0998; found 255.0997.
Compound 17: White solid, mp 68–72 °C. 1H NMR (400 MHz, CDCl3) 1.01–1.09
(m, 2H), 1.23 (s, 3H), 1.44–1.45 (m, 2H), 1.57–1.67 (m, 3H), 1.99–2.03 (m, 1H),
2.66–2.83 (m, 2H), 3.61–3.66 (t, J = 8.0 MHz, 1H), 6.11 (d, J = 1.2 Hz, 1H), 6.33–
6.34 (m, 1H), 7.37 (s,1H). 13C NMR (CDCl3, 100 MHz): d 16.68, 20.79, 23.67,
28.61, 31.50, 37.05, 41.59, 45.83, 80.35, 107.24, 110.30, 141.80, 153.96,
215.14 ppm. HRMS: (ESI) calcd for
257.1147.
C
14H16O2 [M+Na]+ 257.1154; found
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