58579-51-4 Usage
Uses
Used in Pharmaceutical Industry:
Anagrelide hydrochloride is used as an antithrombocythemic agent for the treatment of thrombocytosis. It acts as a potent PDE3 inhibitor, which contributes to its antiplatelet activity. Anagrelide hydrochloride was initially tested as a platelet aggregation inhibitor due to its anti-cAMP phosphodiesterase (PDE III) activity. However, it was discovered that at lower concentrations, it exhibited thrombocytopenic effects. The mechanism of action is not fully understood, but it is known to primarily interfere with the maturation of megakaryocytes, leading to a reduction in size and altered ploidy. Additionally, it has been shown to decrease peripheral vascular resistance and exhibit a positive inotropic effect.
Used in Research and Development:
Anagrelide hydrochloride is also utilized in research and development for studying its effects on platelet aggregation, signal transduction, and its potential applications in various medical conditions related to blood clotting and platelet function. Its role as a PDE3 inhibitor makes it a valuable compound for investigating the underlying mechanisms of platelet activation and the development of novel therapeutic strategies for thrombotic disorders.
Originator
Roberts (US)
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.
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 MAKING ANAGRELIDE
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Page/Page column 12, (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 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 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.
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.
Synthesis and Reactions of 2-Chloro-3,4-dihydrothienopyrimidines and -quinazolines
Yamaguchi, Hitoshi,Ishikawa, Fumiyoshi
, p. 67 - 70 (2007/10/02)
Reaction of 2,4-dichlorothienopyrimidines and -quinazolines 1 with sodium borohydride gave the corresponding 2-chloro-3,4-dihydro derivatives 2.Some nucleophilic substitutions of 2b afforded 2-substituted derivatives 3b-7b and reaction of 2g,h with ethyl bromoacetate yielded selectively the corresponding 3-substituted compounds 8g,h which were derived to imidazoquinazolin-2-ones 9g,h.
Alkyl 5,6-dichloro-3,4-dihydro-2(1H)-iminoquinazoline-3-acetate hydrohalides
-
, (2008/06/13)
The known blood platelet antiaggregative agent 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-one is prepared in high yield via an improved process involving a novel intermediate of the Formula STR1 in which R1 is (lower)alkyl and X is bromo, chloro or iodo. Two processes for the preparation of compounds of the Formula III are disclosed, one of which involves the novel intermediate STR2
