Proline derivatives and their application in the preparation of drugs for treating cardiovascular and cerebrovascular diseases
A technology for cardiovascular and cerebrovascular diseases and derivatives, applied in the field of medicine, can solve the problems of low bioavailability, short half-life of stachydrine, poor anti-ischemic stroke activity, etc., and achieve the effect of inhibiting cytotoxicity
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Examples
Embodiment 1
[0048] Embodiment 1: the synthetic route of N-methyl-L-proline b is as follows:
[0049]
[0050] Dissolve L-proline (4.0 g, 34.8 mmol) in methanol (40 mL), add 40% aqueous formaldehyde solution (2.8 mL, 38.2 mmol) and 10% palladium on carbon (1 g) in turn, add hydrogenation, at room temperature The reaction was carried out for 24 hours. After the reaction was completed, it was filtered, and the mother liquor was concentrated to dryness to obtain 4 g of white solid with a yield of 89%, which was N-methyl-L-proline (compound b). ESI-MS: (m / z, %)=130 [M+H] + .
Embodiment 2
[0051] Embodiment 2: The synthetic route of compound B-4 is as follows:
[0052]
[0053] The N-methyl-L-proline b (1.29 g, 10 mmol) was added to dichloromethane (20 mL), followed by DCC (2.47 g, 12 mmol) and glycine (0.75 g, 10 mmol), and reacted at room temperature for 24 hours, filtered, and concentrated the mother liquor to obtain 1 g of white solid with a yield of 54%, which was compound B-4. 1 H NMR (500MHz, CD 3 OD)δ=4.14(t,J=8.3,1H),4.00(s,2H),3.71(ddd,J=11.4,7.7,4.1,1H),3.22(d,J=11.1,1H),2.95( d, J=10.5, 3H), 2.58 (dd, J=12.2, 7.5, 1H), 2.24-2.02 (m, 3H).
Embodiment 3
[0054] Embodiment 3: the synthetic route of compound B-5 is as follows:
[0055]
[0056] The B-4 (1.86 g, 10 mmol) was added to dichloromethane (20 mL), followed by DCC (2.47 g, 12 mmol) and Y5 (3.1 g, 10 mmol), reacted at room temperature for 24 hours, filtered, and the mother liquor was concentrated to obtain no residue. The color oily substance was 1.4 g, the yield was 30%, which was compound B-5. ESI-MS: (m / z, %)=480 [M+H] + . 1 H NMR (500MHz, D 2 O)δ=7.43(s, 2H), 4.49(d, J=7.8Hz, 2H), 4.42(t, J=6.5Hz, 2H), 4.31(t, J=8.5Hz, 1H), 3.92(s) ,6H),3.85-3.80(m,1H),3.31-3.25(m,3H),2.99(s,3H),2.68-2.61(m,1H),2.32-2.04(m,3H),1.94-1.84 (m, 2H), 1.80–1.73 (m, 2H).
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Description
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Application Information
- IPC
- C07D207/16; A61P9/10; A61P25/00; A61P9/00
- CPC
- C07D207/16; A61P9/10; A61P25/00; A61P9/00; A61K31/401
- Inventors
- 李文保; 李峰