58579-51-4 Usage
Description
Anagrelide hydrochloride, a member of the imidazo[2,1-b]quinazolin-2-one series of compounds, is an off-white powder. It is the hydrochloride salt of anagrelide and is known by the brand name Agrylin (Shire). Anagrelide hydrochloride is a phosphodiesterase inhibitor with antiplatelet activity, which has been used for the treatment of thrombocytosis, particularly essential thrombocytosis or that associated with chronic myelogenous leukemia.
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 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.
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.