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Anagrelide

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Anagrelide Basic information

Product Name:
Anagrelide
Synonyms:
  • ANAGRELIDE
  • 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)one
  • 6,7-Dichloro-5,10-dihydro-3H-imidazo[2,1-b]quinazolin-2-one
  • Anagrelidebase
  • 6,7-dichloro-1,5-dihydroiMidazo 2,1-b quinaz...
  • IMidazo[2,1-β]quinazolin-2(3H)-one,6,7-dichloro-1,5-dihydro-
  • 6,7-Dichloro-5,10-dihydroimidazo[2,1-b]quinazolin-2(3H)-one
  • Anagrelide analogue: 6-chloro-1,2,3,5-tetrahydro iMidazo [2,1-b]quinazolin-2-one
CAS:
68475-42-3
MF:
C10H7Cl2N3O
MW:
256.09
EINECS:
1312995-182-4
Product Categories:
  • Pharmaceutical intermediate
Mol File:
68475-42-3.mol
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Anagrelide Chemical Properties

Melting point:
280 °C
Density 
1.77±0.1 g/cm3(Predicted)
storage temp. 
2-8°C
pka
pKa 2.87 (H2O t=25 I=0.025) (Uncertain);10(H2O t=25 I=0.025) (Uncertain)
Water Solubility 
slightly soluble
CAS DataBase Reference
68475-42-3(CAS DataBase Reference)
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Safety Information

Hazardous Substances Data
68475-42-3(Hazardous Substances Data)
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Anagrelide Usage And Synthesis

Originator

Agrylin,Shire Pharmaceuticals

Uses

the treatment of primary thrombocytosis

Uses

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.

Manufacturing Process

6,7-Dicloro-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-one was produced from 6-chloro-7-bromo-1,2,3,5-tetrahydroimidazo[2,1-b]quinozolin-2-one by substitution the bromine an equimolar quantity chlorine.
6-Chloro-7-bromo-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-one was produced next way: to a solution of 1.30 g (8 mmole) of anhydrous ferric chloride in 30 ml of nitromethane was added 1.30 g (5 mmole) of solid 6- chloro-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-one and 0.80 g (5 mmole) of bromine. The system was stoppered, warmed to 50°C in an oil bath overnight, cooled to room temperature and the solvent removed in vacuo. The resulting solid was suspended in water (50 ml), the mixture was made basic (pH=10) with sodium bicarbonate and stirred at home temperature for 20 min. The solid was filtered under suction, washed with water, then isopropyl alcohol and dried yielding 1.19 g of 6-chloro-7-bromo- 1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-one (78% yield). Purification was effected by formation of the hydrochloride salt (mp 275°C) from acetonitrile.
6-Chloro-1,2,3,5,-tetrahydroimidazo[2,1-b]quinazolin-2-one was produced from 6-chloro-2-nitrobenzylchloride, ethylglycine hydrochloride and cyanogen bromide in 3 steps.

brand name

Agrylin (Shire).

Therapeutic Function

Platelet aggregation inhibitor

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.

AnagrelideSupplier

LGM Pharma
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1-(800)-881-8210
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inquiries@lgmpharma.com
Nanjing Chemlin Chemical Co., Ltd
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025-83697070 13913916777;
Email
info@chemlin.com.cn
BOC Sciences
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1-631-485-4226; 16314854226
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info@bocsci.com
S.Z. PhyStandard Bio-Tech. Co., Ltd.
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4000505016; 13380397412
Email
3001272453@qq.com
Beijing HuaMeiHuLiBiological Chemical
Tel
010-56205725
Email
waley188@sohu.com