NMR characteristics of motesanib and its metabolites M3, M4, M5, M1, and Ma
Metabolitea | |||||||||||||||||||
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| Motesanib | M3 | M4 | M5 | M1 | Ma | ||||||||||||||
| Position | 1H (ppm) (mult, J in Hz) | 13C (ppm) | 1H (ppm) (mult, J in Hz) | 13C (ppm) | 1H (ppm) (mult, J in Hz) | 1H (ppm) (mult, J in Hz) | 1H (ppm) (mult, J in Hz) | 13C (ppm) | 1H (ppm) (mult, J in Hz) | 13C (ppm) | |||||||||
| 1 | 8.45 (d, 6) | 146.5 | 8.28 (d, 6.7)b | 138.0 | 8.46 (d, 6) | 8.46 (m) | 8.45 (d, 6) | 148.1 | 8.44 (br) | 148.0 | |||||||||
| 2 | 7.43 (d, 6) | 123.0 | 7.56 (d, 6.7)b | 124.8 | 7.44 (d, 6) | 7.45 (m) | 7.43 (d, 6) | 122.1 | 7.44 (d, 6.1) | 122.3 | |||||||||
| 3 | 4.78 (s) | 43.1 | 4.78 (s) | 42.2 | 4.8 (s) | 4.82 (s) | 4.79 (s) | 42.7 | 4.78 (s) | 42.8 | |||||||||
| 4 | 8.12 (dd, 4.7, 1.7) | 150.4 | 8.14 (dd, 4.7, 1.7) | 150.3 | 8.16 (dd, 4.7, 1.7) | 8.16 (dd, 4.7, 1.7) | 8.11 (dd, 4.7, 1.7) | 150.4 | 8.11 (d, 4.2) | 150.5 | |||||||||
| 5 | 6.7 (dd, 7.7, 4.7) | 111.5 | 6.72 (dd, 7.7, 4.7) | 111.4 | 6.73 (dd, 7.7, 4.7) | 6.74 (dd, 7.7, 4.7) | 6.7 (dd, 7.7, 4.7) | 111.3 | 6.69 (dd, 7.8, 5.1) | 111.4 | |||||||||
| 6 | 8.04 (dd, 7.7, 1.7) | 136.7 | 8.04 (dd, 7.7, 1.7) | 136.5 | 8.08 (dd, 7.7, 1.7) | 8.12 (dd, 7.7, 1.7) | 8.06 (dd, 7.7, 1.7) | 136.7 | 8.07 (dd, 7.8,1.6) | 136.4 | |||||||||
| 7 | 7.08 (d, 1.7) | 104.8 | 7.08 (d, 1.7) | 103.5 | 7.51 (m)c | 7.04 (d, 1.7) | 6.89 (d, 1.7) | 101.4 | 7.42 (br) | 116.4 | |||||||||
| 8 | 6.94 (dd, 8.1, 1.7) | 113.4 | 6.94 (dd, 8.1, 1.7) | 112.0 | 7.25 (m)c | 6.9 (dd, 8.1, 1.7) | 7.06 (dd, 8.1, 1.7) | 111.6 | 8.07 (br) | 108.2 | |||||||||
| 9 | 7.02 (d, 8.1) | 121.6 | 7.03 (d, 8.1) | 121.3 | 7.25 (m)c | 7 (d, 8.1) | 6.99 (d, 8.1) | 121.3 | 7.19 (d, 8.2) | 121.8 | |||||||||
| 10 | 1.31 (s) | 26.4 | 1.32 (s) | 26.4 | 1.38 (s) | {1.32, 1.24}d | 1.38 (s) | 25.5 | 1.36 | 27.2 | |||||||||
| 10′ | 1.29 (s) | 27.8 | |||||||||||||||||
| 11 | 3.29 (s) | 60.8 | 3.3 (s) | 61.2 | NA | 4.52 (s) | 3.44, 3.59e | 59.9 | 3.82, 3.92e | 62.0 | |||||||||
| 12 | 4.82 (d, 8.9) | 85.3 | 5.57 (d, 7.1) | 95.2 | |||||||||||||||
| 13 | 3.6 (t, 8.5) | 70.6 | 3.52 (br) | 71.8 | |||||||||||||||
| 14 | 3.53 (t, 8.5) | 77.9 | 3.52 (br) | 76.3 | |||||||||||||||
| 15 | 3.49 (t, 8.5) | 72.3 | 3.48 (br) | 72.1 | |||||||||||||||
| 16 | 3.73 (t, 8.5) | 77.0 | 3.82 (br) | 75.3 | |||||||||||||||
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| 151.3 | |||||||||
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Notations: Br, broad peak; d, doublet; dd, doublet of a doublet; Hz, Hertz; J, scalar coupling; m, multiplet; mult, multiplicity; NA, not available; ppm, parts per million; s, singlet.
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↵ a All spectra were acquired in MeOD-d4 and internally referenced to solvent (CD2HOD) resonance at δH 3.32/δC 47.8 ppm. All signal integrals in 1D 1H NMR spectra were consistent with the spectral assignments.
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↵ b Pseudo doublet, strongly coupled AA′BB′.
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↵ c Strongly coupled ABX spin system.
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↵ d The 2 methyls are diastereotopic.
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↵ e AB multiplet.