Proton-NMR of metabolites of omapatrilat isolated from human urine
| Metabolite | 1H NMR Reported in (δ) ppm4-a4-b |
|---|---|
| M1 | 7.25–7.40 (m, 5H, C-1 to C-5), 3.82–3.95 (bm, 1H, C-8), 3.20 (d, 2H, C-7), 2.62 (s, 3H, C-10) |
| M2 | 7.20–7.30 (m, 5H, C-1 to C-5), 3.55 (t, 1H, C-8), 3.22–3.28 (m, 2H, C-7), 2.55 (s, 3H, C-10) |
| M4 | 7.25–7.31 (m, 5H, C-1 to C-5), 5.52 (t, 1H, C-1′), 3.90 (t, 1H, C-5′), 3.62 (t, 1H, C-8), 3.50–3.54 (m, 1H, C-4′), 3.44–3.48 (m, 1H, C-3′), 3.36–3.40 (m, 1H, C-2′), 3.23–3.34 and 2.97–3.01 (2 m, 2H, C-7), 2.17 (3H, C-10) |
| M5 and M64-c | 7.81 and 7.42 (2 d, 1H, proton on N-12 of diastereomers), 7.23–7.35 (m, 5H, C-1 to C-5), 5.43–5.46 (m, 1H, C-17), 4.99–5.05 (m, 2H, C-23 and C-13), 4.28–4.45 and 3.78–3.86 (2 m, 1H, C-8 proton of diastereomers), 3.23–3.27 (m, 2H, C-15), 2.91–2.95, 3.00–3.10, and 3.12–3.21 (3 m, 2H, C-7 protons of diastereomers), 2.57 and 2.63 (2 s, 3H, C-10 protons of diastereomers), 1.37–2.19 (8H, methylenes of C-14 and C-20 to C-22)4-d |
| M8 | 7.60 (d, 1H, N-12), 7.23–7.31 (m, 5H, C-1 to C-5), 5.47–5.54 (m, 2H, C-17 and C-1′), 5.11–5.13 (m, 1H, C-23), 4.99–5.01 (m, 1H, C-13), 3.86 (t, 1H, C-5′), 3.58 (t, 1H, C-8), 3.39–3.43 (m, 2H, C-4′ and C-3′), 3.34–3.38 (m, 1H, C-2′), 3.17–3.25 (m, 2H, C-15), 3.08–3.12 and 2.94–2.98 (2 m, 2H, C-7), 2.10 (s, 3H, C-10), 1.32–2.20 (8H, methylenes of C-14 and C-20 to C-22)4-d |
| M9 | 7.54 (d, 1H, N-12), 7.23–7.31 (m, 5H, C1–5), 5.47–5.49 (m, 1H, C-17), 5.02–5.05 (m, 1H, C-23), 4.98–5.02 (m, 1H, C-13), 3.55 (t, 1H, C-8), 3.18–3.22 (m, 2H, C-15), 2.92–2.98 (m, 2H, C-7), 2.10 (s, 3H, C-10), 1.60–2.30 (8H, methylenes of C-14 and C-20 to C-22)4-d |
↵4-a Proton NMR of M1, M4, mixture of M5 and M6, M8, and M9 were done in acetonitrile-d3, whereas1H NMR of M2 was done in deuterium oxide.
↵4-b The numbers and alphabets in parentheses after the ppm value denote the following: 1) The first alphabet indicates the splitting pattern, for example, m = multiplets, bm = broad multiplet, d = doublet, s = singlet, t = triplet. 2) The second number and alphabet indicate the number of protons in that peak, for example, 3H means three protons. 3) The third letter indicates the atom to which the proton is attached. The number corresponds to numbering of the atoms in Fig. 5 of metabolite M8. The glucuronide carbons are numbered from C-1′ to C-5′.
↵4-c The 1H NMR of metabolite mixture M5 and M6 had other peaks, four multiplets between 3.30 to 3.65 ppm and one multiplet at 5.45 to 5.50 ppm, which correspond to the protons of a glucuronide. Because mass spectrum showed that M5 and M6 were not glucuronides, the extra peaks probably came from an endogenous glucuronide impurity in M5 and M6.
↵4-d The methylene protons from 1.90 to 2.10 ppm on C-14 and C-20 to C-22 were inferred from the COSY spectrum because in 1H NMR these peaks were buried under the solvent peaks.