On the other hand, the Pvalue for 3m corresponds to those of standard drugs with high CNS permeability (Table 6). Table 6 Prediction of the BBB penetration of drugs expressed as the apparent permeability coefficient (P SEM (10?6 cm s?1) /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ CNS (+/?) a /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ N b /th /thead 3e 13.51 1.54CNS ?3 3n 14.61 1.88CNS ?3 3c 12.28 2.33CNS ?3 3m 18.48 2.37CNS +4THA22.29 2.01CNS +4Donepezil24.19 2.83CNS +4Rivastigmine28.63 4.64CNS +5Propranolol23.06 2.06CNS +5Antipyrine17.19 1.82CNS +3Furosemide13.89 0.92CNS ?3Obidoxime14.35 0.52CNS ?4 Open in a separate window a CNS+ and CNS? represent the final predictions of the compound capability to cross or not to cross the BBB, respectively. 1.68C1.59 (m, 2H), 1.50 (m, = 15.0, 5.3, 4.4 Hz, 3H), 1.13C1.00 (m, 3H). 13C-NMR (126 MHz, dmso) 141.09, 138.37, 130.15, 128.09, 127.00, 120.94, 57.68, 54.59, 29.72, 24.68, 23.99. HRMS (ESI+): [M + H]+: calculated for C19H22N+ (= 7.6, 1.0 Hz, 2H), 7.94 (dd, = 7.6, 1.0 Hz, 2H), 7.53 (td, = 7.6, 1.0 Hz, 2H), 7.41 (td, = 7.6, 1.0 Hz, 2H), 5.63 (s, 1H), 2.25C2.15 (m, 1H), 0.85C0.76 (m, 2H), 0.55C0.46 (m, 2H). 13C-NMR (126 MHz, dmso) 141.38, 138.07, 130.14, 127.95, 127.08, 120.82, 60.17, 26.24, 3.50. HRMS (ESI+): [M + H]+: calculated for C16H16N+ (= 7.6, 1.0 Hz, 2H), 7.92 (dd, = 7.6, 1.0 Hz, 2H), 7.52 (td, = 7.6, 1.0 Hz, 2H), 7.40 (td, = 7.6, 1.0 Hz, 2H), 5.57 (s, 1H), 3.12 (p, = 9.1, 8.6 Hz, 1H), 2.22C2.10 (m, 2H), 1.62C1.41 (m, 4H). 13C-NMR (126 MHz, dmso) 141.23, 137.87, 130.16, 127.97, 126.96, 120.84, 58.50, 47.72, 27.67, 15.64. HRMS (ESI+): [M + Alpha-Naphthoflavone H]+: calculated for C17H18N+ (= 7.6, 1.0 Hz, 2H), 7.94 (dd, = 7.6, 1.0 Hz, 2H), 7.55 (td, = 7.6, 1.0 Hz, 2H), 7.42 (td, = 7.6, 1.0 Hz, 2H), 5.72 (s, 1H), 3.23 (d, = 11.7 Hz, 2H), 2.79 (q, = 11.7 Hz, 2H), 2.07 (q, = 12.6, 11.7 Hz, 2H), 1.67 (d, = 12.6 Alpha-Naphthoflavone Hz, 3H), 1.34C1.20 (m, 1H). 13C-NMR (126 MHz, dmso) 141.83, 135.94, 130.66, 128.29, 128.17, 120.91, 67.23, 49.46, 22.29, 21.67. HRMS (ESI+): [M + H]+: calculated for C18H20N+ (= 7.6, 1.0 Hz, 2H), 7.93 (dd, = 7.6, 1.0 Hz, 2H), 7.53 (td, = 7.6, 1.0 Hz, 2H), 7.42 (td, = 7.6, 1.0 Hz, 2H), 5.59 (s, 1H), 3.47 (t, = 5.2 Hz, 2H), 3.19 (s, 3H), 2.47C2.40 (m, 2H). 13C-NMR (126 MHz, dmso) 141.42, 137.56, 130.27, 128.26, 126.69, 120.93, 67.03, 59.32, 58.16, 40.87. HRMS (ESI+): [M + H]+: calculated for C16H18NO+ (= 9.3 Hz, 2H), 8.12 Alpha-Naphthoflavone (dd, = 7.6, 1.0 Hz, 2H), 7.94 (dd, = 7.6, 1.0 Hz, 2H), 7.53 (td, = 7.6, 1.0 Hz, 2H), 7.42 (td, = 7.6, 1.0 Hz, 2H), 5.61 (d, = 3.5 Hz, 1H), 2.51C2.48 (m, 2H), 1.14 (t, = 7.2 Hz, 3H). 13C-NMR (126 MHz, dmso) 141.29, 137.89, 130.19, 128.18, 126.72, 120.91, 59.17, 37.35, 11.53. HRMS (ESI+): [M + H]+: calculated for C15H16N+ (= 7.6, 1.0 Hz, 2H), 7.98 (dd, = 7.6, 1.0 Hz, 2H), 7.57 (td, = 7.6, 1.0 Hz, 2H), 7.44 (td, = 7.6, 1.0 Hz, 2H), 5.85 (s, 1H), 3.12C3.02 (m, 1H), 3.02C2.94 (m, 1H), 1.30 (t, = 7.2 Hz, 6H). 13C-NMR (126 MHz, dmso) 141.62, 136.45, 130.54, 128.37, 127.49, 121.07, 63.15, 46.29, 10.32. HRMS (ESI+): [M + H]+: calculated for C17H20N+ (= 7.6, 1.0 Hz, 2H), 7.59 (dd, = 7.6, 1.0 Hz, 2H), 7.42 (td, = 7.6, 1.0 Hz, 2H), 7.34 (td, = 7.6, 1.0 Hz, 2H), 5.03 (s, 1H), 3.31C2.71 (m, 8H), 2.68 (s, 3H). 13C-NMR (126 MHz, dmso) 143.00, 140.64, 128.64, 127.51, 125.88, 120.36, 68.65, 53.41, 45.50, 42.34. HRMS (ESI+): [M + H]+: calculated for C18H21N2+ (= 7.6, 1.0 Hz, 2H), 7.59 (dd, = 7.6, 1.0 Hz, Alpha-Naphthoflavone 2H), 7.42 (td, = 7.6, 1.0 Hz, 2H), 7.33 (td, = 7.6, 1.0 Hz, 2H), 5.03 (s, 1H), 3.02 (q, = 7.3 Hz, 2H), 2.99C2.61 (m, 8H), 1.19 (t, = 7.3 Hz, 3H). 13C-NMR (126 MHz, dmso) 143.05, 140.63, 128.62, 127.49, 125.90, 120.34, 68.67, 51.28, 50.79, 45.45, 9.01. HRMS (ESI+): [M + H]+: calculated for C19H24N2+ (m/z): 279.18612; found: 279.18555. LC-MS purity 99%. 2.2.12. 4-(9= 7.6, 1.0 Hz, 2H), 7.96 (dd, = 7.6, 1.0 Hz, 2H), 7.58 (td, = 7.6, 1.0 Hz, 2H), 7.45 (td, = 7.6, 1.0 Hz, 2H), Hepacam2 5.81 (s, 1H), 4.18C3.93 (m, 2H), 3.94C3.75 (m, 2H), Alpha-Naphthoflavone 3.31C3.09 (m, 2H), 3.09C2.87 (m, 2H). 13C-NMR (126 MHz, DMSO) 142.19, 131.09, 128.60, 128.46, 121.30, 67.38, 63.41, 48.58. HRMS (ESI+): [M + H]+: calculated for C17H18NO+ (= 7.6, 1.0 Hz, 2H), 7.93 (dd, = 7.6, 1.0 Hz, 2H), 7.52 (td, = 7.6, 1.0 Hz, 2H), 7.42 (td, = 7.6, 1.0.
Categories:mGlu Group III Receptors