58579-51-4 Usage
Description
Anagrelide hydrochloride was launched in the US for thrombocytosis (essential or associated with chronic myelogenous leukemia). The imidazoquinazoline derivative can be prepared from 2,5,6-trichloro-3,4-dihydropyrimidine via alkylation with ethyl bromoacetate followed by heating with ethanolic ammonia or treatment of N-(a-amino- 5,6-dichlorobenzyl)glycine ethyl ester with cyanogen bromide. As a result of its anti-cAMP phosphodiesterase (PDE Ⅲ) activity, Anagrelide hydrochloride was initially tested as a platelet aggregation inhibitor. However it was found that at much lower concentrations it became thrombocytopenic. While the mechanism is not fully understood, it did not shorten platelet survival nor inhibit the formation of colony-forming unitsmegakaryocytes (CFU-M) but primarily interfered with the maturation of megakaryocytes (reduction in size with altered ploidy). It did decrease peripheral vascular resistance and had a positive inotropic effect.
Chemical Properties
Off-White Powder
Originator
Roberts (US)
Uses
Different sources of media describe the Uses of 58579-51-4 differently. You can refer to the following data:
1. A phosphodiesterase inhibitor with antiplatelet activity. Used as an antithrombocythemic.
2. Signal Transduction Agents, Potent PDE3 inhibitor
3. Anagrelide Hydrochloride is a phosphodiesterase inhibitor with antiplatelet activity. Used as an antithrombocythemic. Potent PDE3 inhibitor.
Definition
ChEBI: The hydrochloride salt of anagrelide.
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).
General Description
Anagrelide belongs to the imidazo[2,1-b]quinazolin-2-one series of compounds.
Biological Activity
Potent type III phosphodiesterase (PDE3) inhibitor (IC 50 = 36 nM). Inhibits platelet aggregation and produces potent thrombocytopenic effects via inhibition of megakaryocyte maturation.
Biochem/physiol Actions
Anagrelide is a phosphodiesterase inhibitor with antiplatelet activity (IC50 = 36 nM for inhibition of phosphodiesterase-III). Anagrelide inhibits the maturation of megakaryocytes into platelets, reducing both megakaryocyte hyperproliferation and differentiation. As a drug, anagrelide is antithrombocythemic used for the treatment of overproduction of blood platelets.
References
1) Gilespie?et al.?(1988),?Anagrelide: a potent and selective inhibitor of platelet cyclic AMP phosphodiesterase enzyme activity; Biochem. Pharmacol.?37?2866
2) Mazur?et al.?(1992),?Analysis of the mechanism of anagrelide-induced thrombocytopenia in humans; Blood,?79?1931
3) Wang?et al.?(2005),?Comparison of the biological activities of anagrelide and its major metabolites in haematopoietic cell cultures; Br. J. Pharmacol.,?146?324
4) Barbui?et al.?(2012),?Front-line therapy in polycythemia vera and essential thrombocythemia; Blood Rev.,?26?205
5) Chen?et al.?(2012),?Platelet-lowering therapy with anagrelide as an adjuvant therapy for treatment of primary pulmonary neoplasm-associated extreme thrombocytosis; Jpn. J. Clin. Oncol.,?42?761
Check Digit Verification of cas no
The CAS Registry Mumber 58579-51-4 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,8,5,7 and 9 respectively; the second part has 2 digits, 5 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 58579-51:
(7*5)+(6*8)+(5*5)+(4*7)+(3*9)+(2*5)+(1*1)=174
174 % 10 = 4
So 58579-51-4 is a valid CAS Registry Number.
InChI:InChI=1/C10H7Cl2N3O.ClH/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);1H
58579-51-4Relevant articles and documents
PROCESS FOR MAKING ANAGRELIDE
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Page/Page column 14, (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 4, (2010/12/29)
The present invention relates to a process for preparation of Anagrelide Hydrochloride Monohydrate.
USE OF 2-AMINO-2H-QUINAZOLINE DERIVATIVES FOR PRODUCING THERAPEUTIC AGENTS
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Page/Page column 12, (2010/02/07)
The invention relates to the use of 2-amino-2H-quinazoline derivatives of general chemical formula (I), wherein R1 represents an alkyl group having 1 - 5 carbon atoms and R2, R3, R4 and R5 independently represent a chlorine or hydrogen atom, in addition to the pharmaceutically compatible salts thereof for producing therapeutic agents for treating myeloproliferative diseases, high blood pressure and bronchodilation.
