Journal of Medicinal Chemistry
Article
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Inhibitor 13c. H NMR (300 MHz, D2O) δ 7.77 (d, J = 5.6 Hz,
HRMS: calcd for C13H17N2O7P2 m/z 375.0506 (M + H+)+; found
m/z 375.0492.
Inhibitor 13k. H NMR (300 MHz, D2O) δ 7.76 (d, J = 5.7 Hz,
1H), 7.62 (dd, J = 8.4, 1.8 Hz, 1H), 7.28−7.39 (m, 3H), 6.71 (s, 1H),
6.66 (d, J = 5.6 Hz, 1H), 3.79 (t, J = 21.3 Hz, 1H).
13C NMR (75 MHz, D2O) δ 161.79, 152.30, 149.69, 141.02, 131.50,
129.44, 112.32, 107.76, 54.71 (CH, J = 114.0 Hz).
31P NMR (81 MHz, D2O) δ 16.52.
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1H), 7.60 (d, J = 8.7 Hz, 2H), 6.95 (d, J = 8.7 Hz, 2H), 6.81 (s, 1H),
6.74 (d, J = 5.7 Hz, 1H), 3.88 (t, J = 19.5 Hz, 1H), 1.19 (d, J = 6.0 Hz,
6H).
HRMS: calcd for C12H15N2O6P2 m/z 345.0400 (M + H+)+; found
m/z 345.0393.
13C NMR (75 Hz, D2O) δ 158.03, 157.81, 149.86, 144.92, 130.73,
128.40, 116.57, 110.23, 105.61, 71.55, 51.67 (CH, t, J = 126.11 Hz),
20.95.
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Inhibitor 13d. H NMR (300 MHz, D2O) δ 8.20 (s, 1H), 7.79−
31P NMR (81 MHz, D2O) δ 15.26.
7.91 (m, 5H), 7.45−7.47 (m, 2H), 6.95 (s, 1H), 6.87 (d, J = 5.7 Hz,
1H), 3.92 (t, J = 19.3 Hz, 1H).
HRMS: calcd for C15H21N2O7P2 m/z 403.0819 (M + H+)+; found
m/z 403.0812.
13C NMR (75 MHz, D2O) δ 158.93, 149.86, 146.64, 135.68, 133.08,
133.05, 128.55, 128.36, 127.55, 126.87, 126.72, 126.14, 124.75, 110.36,
105.79, 51.99 (CH, t, J = 125.0 Hz).
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Inhibitor 13l. H NMR (500 MHz, D2O) δ 7.78 (d, J = 5.5 Hz,
1H), 7.61 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 6.84 (s, 1H),
6.77 (d, J = 5.5 Hz, 1H), 3.92 (t, J = 18.0 Hz, 1H), 2.33−2.37 (m, 2H),
1.95−2.03 (m, 2H), 1.69−1.72 (m, 1H), 1.55−1.61 (m, 1H).
13C NMR (125 Hz, D2O) δ 157.96, 157.57, 149.95, 144.76, 130.67,
128.44, 115.51, 110.35, 105.72, 72.10, 51.59 (CH, t, J = 123.8 Hz),
29.86, 12.45.
31P NMR (81 MHz, D2O) δ 15.56.
HRMS: calcd for C16H15N2O6P2 m/z 393.0411 (M − H+)−; found
m/z 393.0416.
Inhibitor 13e. 1H NMR (500 MHz, D2O) δ 8.73 (s, 1H), 8.43 (d, J
= 5.1 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.88 (d, J = 5.5 Hz, 1H), 7.42
(dd, J = 8.0, 5.0 Hz, 1H), 6.85 (s, 1H), 6.77 (d, J = 5.1 Hz, 1H), 3.94
(t, J = 18.6 Hz, 1H).
31P NMR (81 MHz, D2O) δ 15.19.
HRMS: calcd for C16H19N2O7P2 m/z 413.0673 (M − H+)−; found
m/z 413.0667.
13C NMR (125 MHz, D2O) δ 158.71, 148.69, 146.84, 135.84,
134.52, 128.11, 124.30, 110.34, 106.07, 51.37 (CH, t, J = 130.0 Hz).
31P NMR (81 MHz, D2O) δ 15.48.
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Inhibitor 13m. H NMR (300 MHz, D2O) δ 7.75 (d, J = 5.7 Hz,
1H), 7.17−7.21 (m, 4H), 6.51 (s, 1H), 6.45 (d, J = 5.7 Hz, 1H), 3.87
HRMS: calcd for C11H12N3O6P2 m/z 344.0207 (M − H+)−; found
m/z 344.0215.
(CH, t, J = 19.2 Hz, 1H), 2.13 (s, 3H).
13C NMR (75 MHz, D2O) δ 157.75, 151.92, 144.55, 139.41, 135.40,
130.42, 128.89, 128.38, 125.95, 113,26, 109.26, 51.38 (CH, t, J = 124.5
Hz), 19.22.
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Inhibitor 13f. H NMR (300 MHz, D2O) δ 8.06 (s, 1H), 8.01 (s,
1H), 7.74 (d, J = 5.7 Hz, 1H), 7.46−7.55 (m, 2H), 6.74 (s, 1H), 6.71
(d, J = 5.7 Hz, 1H), 3.77 (t, J = 18.0 Hz, 1H).
13C NMR (75 MHz, D2O) δ 161.79, 153.25, 149.91, 149.53, 137.23,
131.63, 126.14, 125.94, 121.64, 116.34, 112.45, 107.47, 54.63 (CH, t, J
= 171.0 Hz).
31P NMR (81 MHz, D2O) δ 15.35.
HRMS: calcd for C13H15N2O6P2 m/z 357.0411 (M − H+)−; found
m/z 357.0420.
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Inhibitor 13n. H NMR (300 MHz, D2O) δ 7.77 (d, J = 5.9 Hz,
31P NM (81 MHz, D2O) δ 16.70.
1H), 7.47 (s, 1H), 7.41 (d, J = 7.6 Hz, 1H), 7.26 (dd, J = 7.6, 7.6 Hz,
1H), 7.17 (d, J = 7.6 Hz, 1H), 6.84 (s, 1H), 6.76 (d, J = 5.9 Hz, 1H),
3.90 (t, J = 18.9 Hz, 1H), 2.24 (s, 3H).
HRMS: calcd for C13H15N4O6P2 m/z 385.0461 (M + H+)+; found
m/z 385.0457.
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Inhibitor 13g. H NMR (300 MHz, D2O) δ 8.01 (s, 1H), 7.70−
13C NMR (75 Hz, D2O) δ 157.98, 150.74, 144.87, 139.22, 137.88,
129.93, 128.99, 127.47, 123.94, 110.84, 106.43, 51.39 (CH, t, J = 120.0
Hz), 20.31.
7.77 (m, 2H), 7.43 (d, J = 8.7 Hz, 1H), 6.85 (s, 1H), 6.76 (d, J = 5.1
Hz, 1H), 3.82 (t, J = 19.2 Hz, 1H).
13C NMR (75 MHz, D2O) δ 162.45, 157.70, 151.23, 146.57, 144.32,
132.98, 122.62, 116.42, 114.61, 110.89, 106.62, 51.96 (CH, t, J =
121.50 Hz).
31P NMR (81 MHz, D2O) δ 15.22.
HRMS: calcd for C13H15N2O6P2 m/z 357.0411 (M − H+)−; found
m/z 347.0418.
31P NMR (81 MHz, D2O) δ 15.14.
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Inhibitor 13o. H NMR (300 MHz, D2O) δ 7.80 (d, J = 5.7 Hz,
HRMS: calcd for C12H12N5O6P2 m/z 384.0268 (M − H+)−; found
m/z 384.0270.
1H), 7.57 (d, J = 8.1 Hz, 2H), 7.24 (d, J = 8.1 Hz, 2H), 6.84 (s, 1H),
6.77 (d, J = 5.7 Hz, 1H), 3.92 (t, J = 19.5 Hz, 1H), 2.25 (s, 3H).
13C NMR (75 Hz, D2O) δ 158.29, 150.24, 145.50, 134.99, 129.62,
126.83, 110.46, 105.27, 51.50 (CH, t, J = 227.5 Hz), 20.18.
31P NMR (81 MHz, D2O) δ 15.39; HRMS:calcd for C13H15N2O6P2
m/z 357.0411 (M − H+)−; found m/z 357.0402.
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Inhibitor 13h. H NMR (300 MHz, D2O) δ 7.71 (d, J = 5.7 Hz,
1H), 7.25−7.32 (m, 2H), 6.92−7.01 (m, 2H), 6.92 (s, 1H), 6.61 (d, J
= 5.7 Hz, 1H), 3.86 (t, J = 18.0 Hz, 1H), 3.66 (s, 3H).
13C NMR (75 MHz, D2O) δ 161.49, 157.40, 155.73, 148.82, 143.70,
130.40, 130.14, 127.67, 121.34, 113.40, 111.99, 55.48, 51.51 (CH, t, J
= 134.03 Hz).
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Inhibitor 13p. H NMR (500 MHz, D2O) δ 7.81 (d, J = 5.2 Hz,
31P NMR (81 MHz, D2O) δ 15.19.
1H), 7.61 (d, J = 8.3 Hz, 2H), 7.34 (d, J = 8.3 Hz, 2H), 6.87 (s, 1H),
6.80 (d, J = 5.2 Hz, 1H), 3.95 (t, J = 19.5 Hz, 1H), 2.86 (septet, J = 7.0
Hz, 1H), 1.13 (d, J = 6.9 Hz, 6H).
HRMS: calcd for C13H15N2O7P2 m/z 373.0360 (M − H+)−; found
m/z 373.0367.
13C NMR (125 Hz, D2O) δ 158.21, 150.91, 150.26, 145.31, 135.45,
127.14, 127.02, 110.59, 105.86, 51.46 (CH, t, J = 131.4 Hz), 33.31,
23.04.
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Inhibitor 13i. H NMR (300 MHz, D2O) δ 7.77 (d, J = 5.7 Hz,
1H), 7.29 (dd, J = 7.6, 7.6 Hz, 1H), 7.20 (d, J = 7.6 Hz, 1H), 7.15 (d, J
= 1.5 Hz, 1H), 6.90 (dd, J = 7.6, 1.5 Hz, 1H), 6.81 (s, 1H), 6.73 (d, J =
5.7 Hz, 1H), 3.91 (t, J = 19.2 Hz, 1H), 3.71 (s, 3H).
13C NMR (75 MHz, D2O) δ 159.19, 158.02, 150.22, 145.17, 139.68,
130.21, 119.80, 114.91, 112.27, 110.83, 106.49, 55.32, 51.35 (CH, t, J
= 122.3 Hz).
31P NMR (81 MHz, D2O) δ 15.32.
HRMS: calcd for C15H19N2O6P2 m/z 385.0724 (M − H+)−; found
m/z 385.0736.
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Inhibitor 13r. H NMR (300 MHz, D2O) δ 8.14 (s, 2H), 7.96 (s,
31P NMR (81 MHz, D2O) δ 15.28.
1H), 7.84 (d, J = 5.6 Hz, 1H), 6.81 (s, 1H), 6.74 (d, J = 5.6 Hz, 1H),
3.88 (t. J = 21.9 Hz, 1H).
HRMS: calcd for C13H15N2O7P2 m/z 373.0360 (M − H+)−; found
m/z 373.0364.
13C NMR (75 MHz, D2O) δ 147.06, 144.05 (C, q, J = 548.8 Hz),
131.16 (C, q, J = 33.0 Hz), 128.76, 127.57−127.70 (CH, m), 125.14,
122.55−122.65 (CH, m), 121.53, 110.31, 105.01, 51.38 (CH, t, J =
120.8 Hz).
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Inhibitor 13j. H NMR (300 MHz, D2O) δ 7.71 (d, J = 6.2 Hz,
1H), 7.55−7.59 (m, 2H), 6.89−6.94 (m, 2H), 6.82 (s, 1H), 6.74 (d, J
= 6.2 Hz, 1H), 3.85 (t, J = 18.9 Hz, 1H), 3.68 (s, 3H).
13C NMR (75 MHz, D2O) δ 159.90, 130.19, 128.35, 114.36, 110.35,
105.96, 55.27, 51.76 (CH, t, J = 121.3 Hz).
31P NMR (81 MHz, D2O) δ 15.46.
HRMS: calcd for C14H11F6N2O6P2 m/z 479.0002 (M − H+)−;
found m/z 479.0020.
31P NMR (81 MHz, D2O) δ 14.91.
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dx.doi.org/10.1021/jm201657x | J. Med. Chem. 2012, 55, 3201−3215