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[摘要]：Metabolism of 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2-one (anagrelide), a drug for treating essential thrombocythemia, gives 6,7-dichloro-3-hydroxy-1,5-dihydroimidazo[2,1-b]quinazolin-2-one (3-hydroxyanagrelide) and 2-amino-5,6-dichloro-3,4-dihydroquinazoline. To enable the properties of 3-hydroxyanagrelide to be fully evaluated, the racemic compound has been synthesized. In pH 7.4 aqueous buffer 3-hydroxyanagrelide readily equilibrates with an isomer, 6,7-dichloro-1-hydroxy-3,5-dihydroimidazo[1,2-alpha]-quinazolin-2-one,and is also hydrolyzed to 2-amino-5,6-dichloro-3,4-dihydroquinazoline. 3-Hydroxyanagrelide (half-life 40 hours) was the dominant species at equilibrium and it was concluded that the equilibration and decomposition are sufficiently slow that published assays of 3-hydroxyanagrelide are reliable. |
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