68475-42-3 Usage
Originator
Agrylin,Shire Pharmaceuticals
Uses
Different sources of media describe the Uses of 68475-42-3 differently. You can refer to the following data:
1. the treatment of primary thrombocytosis
2. Anagrelide; Potent PDE 3 inhibitorIt can be used to inhibit cancer cell invasion.
Definition
ChEBI: A 1,5-dihydroimidazo[2,1-]quinazoline having an oxo substituent at the 2-position and chloro substituents at the 6- and 7-positions.
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 11, (2015/01/16)
The invention relates to a process for the manufacture and purification of pharmaceutically active compound anagrelide of formula (1). The process is based on converting anagrelide or an acid addition salt thereof to a formate salt of anagrelide, in particular to anagrelide hemiformate.
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.
