68475-42-3 Usage
Description
Anagrelide is a synthetic imidazoquinazoline compound that functions as a potent phosphodiesterase 3 (PDE 3) inhibitor. It is primarily used for the treatment of primary thrombocythemia, a rare blood disorder characterized by an abnormally high number of platelets in the blood. Anagrelide works by reducing the production of platelets in the bone marrow, thereby normalizing platelet count and alleviating symptoms associated with the condition.
Uses
Used in Hematology:
Anagrelide is used as a therapeutic agent for the treatment of primary thrombocythemia, a rare blood disorder characterized by an abnormally high number of platelets in the blood. It helps to reduce the production of platelets in the bone marrow, normalizing platelet count and alleviating symptoms associated with the condition.
Used in Oncology:
Anagrelide is used as an inhibitor of cancer cell invasion. Its potent PDE 3 inhibitory activity helps to suppress the invasiveness of cancer cells, potentially reducing the spread of cancer and improving patient outcomes.
Originator
Agrylin,Shire Pharmaceuticals
Clinical Use
Platelet-reducing agent
Enzyme inhibitor
This potent platelet aggregation inhibitor (FW = 256.09 g/mol; CAS 68475-42-3), also known as 6,7-dichloro-1,5-dihydroimidazo[2,1- b]quinazolin-2(3H)-one, BL-4162A, and Agrylin?, blocks the action of a variety of aggregating agents added platelet rich plasma, EC50 < 1 μg/mL, or 4 nM. Primary Mode of Action: Although the exact mechanism of its selective inhibition of megakaryocyte (MK) production of platelets remains uncertain, anagrelide is known to be a potent inhibitor of phosphodiesterase-II (IC50 = 36 nM) and lipoprotein-associated phospholipase A2 (or Lp-PLA2), the latter also known as platelet-activating factor acetylhydrolase (or PAF-AH). PDE-II hydrolyzes both cGMP and cAMP. Binding of cGMP to its regulatory GAF-B domain favors cAMP hydrolysis to 5’-AMP, thereby reducing cGMP hydrolysis to 5’-GMP. This property, which facilitates cross-regulation of the cAMP and cGMP pathways, suggests that a potent PDE-II inhibitor should potentiate the effects of cAMP and/or cGMP, the concentrations of which should increase in anagrelide-sensitive cells. Lp-PLA2 plays pivotal role in platelet maturation by specifically hydrolyzing Platelet-Activating Factor (PAF = acetyl-glyceryl-ether-phosphorylcholine) as well as other glycerophos-pholipids containing short, truncated, and/or oxidized fatty acyl groups at the sn-2 position of the glycerol backbone. At a final concentration of 100 ng/mL, anagrelide selectively blocks in vitro MK maturation, resulting in a 50% decrease in the total number of CD41a+ MKs. In humans, anagreline has the intriguing ability to promote as a species-specific platelet-lowering activity at dose levels lower than those required to inhibit platelet aggregation. Target(s): collagen- and immune complexinduced platelet aggregation and release; suppresses megakaryocytopoiesis by reducing the expression levels of the transcription GATA-1 and FOG-1 via a PDEIII-independent mechanism that is differentiation context-specific but does not involve inhibition of MPL-mediated early signal transduction events.
Drug interactions
Potentially hazardous interactions with other drugs
Aspirin: potential risks and benefits must first be
assessed, additive antiplatelet effect.
Cilostazol: avoid concomitant use.
Grapefruit juice: may reduce clearance of anagrelide.
Phosphodiesterase inhibitors: avoid with milrinone
and enoximone.
Metabolism
Anagrelide is primarily metabolised by CYP1A2; less
than 1% is recovered in the urine as anagrelide. Two
major urinary metabolites, 2-amino-5, 6-dichloro-3,
4-dihydroquinazoline and 3-hydroxy anagrelide
(pharmacologically active) have been identified.
The mean recovery of 2-amino-5, 6-dichloro-3,
4-dihydroquinazoline in urine is approximately 18-35%
of the administered dose.
Check Digit Verification of cas no
The CAS Registry Mumber 68475-42-3 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,8,4,7 and 5 respectively; the second part has 2 digits, 4 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 68475-42:
(7*6)+(6*8)+(5*4)+(4*7)+(3*5)+(2*4)+(1*2)=163
163 % 10 = 3
So 68475-42-3 is a valid CAS Registry Number.
InChI:InChI=1/C10H7Cl2N3O/c11-6-1-2-7-5(9(6)12)3-15-4-8(16)14-10(15)13-7/h1-2H,3-4H2,(H,13,14,16)
68475-42-3Relevant articles and documents
PROCESS FOR MAKING ANAGRELIDE
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Page/Page column 12, (2014/09/29)
The present invention relates to an improved process for making anagrelide of formula (1), or an acid addition salt thereof, including any hydrated or solvated form thereof, comprising reacting a compound of formula (3), or an acid addition salt thereof, (3), wherein R is a C1-C4 alkyl group, with chloroformamidine hydrochloride of formula (8), in an inert solvent, followed by treatment of the reaction mixture with a base.
Process for the Manufacture of Anagrelide Hydrochloride Monohydrate
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Page/Page column 2; 4, (2010/12/29)
The present invention relates to a process for preparation of Anagrelide Hydrochloride Monohydrate.
METHOD FOR THE PRODUCTION OF ANAGRELIDE HYDROCHLORIDE
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Page/Page column 5-6, (2010/02/13)
Disclosed is a method for producing 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazoline-2(3H)-on hydrochloride (anagrelide hydrochloride). Said method comprises the following steps: a) 2,3-dichlorobenzaldehyde is nitrated to obtain 2,3-dichloro-6-nitrobenzaldehyde; b) 2,3-dichloro-6-nitrobenzaldehyde is reacted with hydroxylamine HCl and acetic anhydride by applying heat so as to obtain 2,3-dichloro-6-nitrobenzonitrile; c) the nitro group of 2,3-dichloro-6-nitrobenzonitrile is reduced to obtain 2,3-dichloro-6-aminobenzonitrile; d) the nitrile group of 2,3-dichloro-6-aminobenzonitrile is reduced to obtain 2,3-dichloro-6-aminobenzylamine dihydrochloride; e) 2,3-dichloro-6-aminobenzylamine dihydrochloride is reacted with i) bromoacetic acid ethyl ester, CH3CN, and triethylamine; and ii) BrCN to obtain (2-amino-5,6-dichloro-4H-quinazoline-3-yl) acetic acid ethyl ester; f) (2-amino-5,6-dichloro-4H-quinazoline-3-yl) acetic acid ethyl ester is reacted in cycloalkylation conditions to obtain 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazoline-2(3H)-on; and g) 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazoline-2(3H)-on is reacted with HCl to obtain anagrelide hydrochloride.