Ozagrel

Ozagrel(OKY-046) is an antiplatelet agent working as a thromboxane A2 synthesis inhibitor.Target: Thromboxane A2 SynthaseOzagrel was selected as the best compound of highly selective inhibitors of TXA2 synthase. The inhibition of TXA2 synthase by ozagrel was more effective on human and rabbit enzymes than those of other species. Ozagrel increased 6-keto-PGF1 alpha, one of stable metabolites of PGI2, in various isolated cells and tissues perhaps via accumulated PG endoperoxides resulted b

Take 282g hydrochloric acid ozagrel monohydrate, add water 1270ml, heated to 60 , dissolved completely, add 1mol / L sodium hydroxide solution 1000ml, cooled to 20 , put it aside for 2 hours, filter, filter cake washed dry Was added to a mixed solution of 300 ml of methanol / 900 ml of purified water, heated to complete dissolution, cooled to 5 ° C, incubated for 4 h, filtered and dried at 50 ° C to obtain 194.3 g of ozagrel.Ozagrel HPLC purity is shown in Fig.Take 282g hydrochloric acid ozagrel monohydrate, add water 1270ml, heated to 60 , dissolved completely, add 1mol / L sodium hydroxide solution 1000ml, cooled to 20 , put it aside for 2 hours, filter, filter cake washed dry Was added to a mixed solution of 300 ml of methanol / 900 ml of purified water, heated to complete dissolution, cooled to 5 ° C, incubated for 4 h, filtered and dried at 50 ° C to obtain 194.3 g of ozagrel.Ozagrel HPLC purity is shown in Fig.A mixture of CuCl2*2H2O (0.017 g, 0.1 mmol), HIMPAA(0.0456 g, 0.2 mmol), NaOH (0.30 mL, 0.65 mol/L), and distilled water (10 mL) was sealed in a Teflon-lined stainless reactor (25 mL) and heated at 120 C for 72 h, and then cooled the autoclave to room temperature. The crystals were recovered, then filtered and washed with distilled water. The blue crystals of 2 were obtained suitable for X-ray diffraction analysis with yield 50 % basedon Cu(II). Elemental Anal. Calcd. (%) for C26H23ClCuN4O4 (554.49): C, 56.22; H, 4.36; N, 10.09. Found(%): C, 55.52; H, 4.45; N, 9.93. IR (KBr, cm-1): 3233.19, 1696.97, 1677.74, 1630.73, 1544.86, 1427.27, 1317.94, 1287.14, 1222.92, 1076.17, 970.53, 948.52, 936.42, 922.90, 954.19, 838.05, 806.23, 800.25, 780.84, 744.42, 740.05, 719.50, 709.34.A mixture of AgNO3 (0.017 g, 0.1 mmol), HIMPAA(0.0228 g, 0.1 mmol), NaOH (0.15 mL, 0.65 mol/L), and distilled water (10 mL) was sealed in a Teflon-linedstainless reactor (25 mL) and heated at 120 C for 72 h, and then cooled the autoclave to room temperature. Thecrystals were recovered, then filtered and washed withdistilled water. The colorless crystals of 1 were obtainedsuitable for X-ray diffraction analysis with yield 40 %based on Ag(I). Elemental Anal. Calcd. (%) for C26H23AgN4O4 (562.08): C, 55.43; H, 4.12; N, 9.95. Found (%):C, 54.56; H, 3.23; N, 9.79. IR (KBr, cm-1): 3139.25, 3118.60, 1693.71, 1510.46, 1437.28, 1416.62, 1362.59, 1294.08, 1244.70, 1204.32, 1116.87, 1087.67, 1029.65, 975.05, 941.23, 877.33, 852.74, 765.13, 725.20, 713.46.At 10-15 C, 60.00g (0.263 mol) meglumine was added to 95% ethanol. Stirring and heating at reflux. Add 57.17g (0.250 mol) (79 g, 0.35 mol), 500 ml of dichloromethane, 5 ml of DMF, With stirring at room temperature, Oxalyl chloride (220 g, 1.75 mol) was added, First 0.5h stirring at room temperature, And then warmed to 45 ~ 50 stirring reaction 2.5h, TLC identification of the end of the reaction [TLC (petroleum ether - ethyl acetate = 10: 2)], the reaction was completed, concentrated to dryness under reduced pressure, the residue was added to 100ml of dichloromethane and then concentrated under reduced pressure to dryness under reduced pressure, So repeated three times, 78.6 g of a pale yellow solid (Intermediate 3), Yield 91%.Take 282g hydrochloric acid

Strong thromboxane synthase inhibitor. By inhibiting thromboxane synthase, it reduces thromboxane A, (TXA2), and promotes the production of prostacyclin (PGl2) to fight platelet aggregation and cerebral vasospasm, and other arachidene such as cyclooxygenase Acid metabolic enzymes have little effect. Clinically used for the treatment of cerebral spasm after subarachnoid hemorrhage and cerebral ischemia accompanied by cerebral spasm, and the improvement of dyskinesia associated with acute stage of cerebral thrombosis.