- Synthesis and stability of 3-hydroxyanagrelide, a biologically potent metabolite of anagrelide
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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-a]- 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.
- Scott, Richard B.,Downey, Kristin M.,Healy, Keith P.,Henderson, Alistair P.,Robinson, Claire L.,Clegg, William,Harrington, Ross W.,Franklin, Richard,Golding, Bernard T.
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p. 1637 - 1646
(2013/08/23)
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- Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: Structure-activity relationship elucidation
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The optimisation of affinity and selectivity in a novel series of dual 5-HT5A/5-HT7 receptor ligands is described. Brain penetrant 2-aminodihydroquinazolines with low nanomolar affinities were identified.
- Peters, Jens-Uwe,Luebbers, Thomas,Alanine, Alexander,Kolczewski, Sabine,Blasco, Francesca,Steward, Lucinda
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p. 256 - 261
(2008/12/23)
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- 2-amino-5,6-dichloro-3,4-dihydroquinazoline, its method of making and using and pharmaceutical compositions thereof
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The compound 2-amino-5,6-dichloro-3,4-dihydroquinazoline has been found to have enhanced platelet count reducing properties. Also provided are methods for synthetically making the compound and a method of reducing the platelet count in a patient by administering to the patient a platelet reducing effective amount of the compound preferably together with a pharmaceutically acceptable carrier. A pharmaceutical composition is also provided which contains the above compound as the active ingredient together with pharmaceutically acceptable excipients.
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