6,7-dichloro-1H,2H,3H,5H-imidazolidino[2,1-b]quinazolin-2-one hydrochloride

• ChemBase ID: 146
• Molecular Formular: C10H8Cl3N3O
• Molecular Mass: 292.54902
• Monoisotopic Mass: 290.97329493
• SMILES: N12C(=Nc3c(C1)c(c(cc3)Cl)Cl)NC(=O)C2.Cl
• Canonical SMILES: O=C1NC2=Nc3c(CN2C1)c(Cl)c(cc3)Cl.Cl
• InChI: InChI=1S/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
• InChIKey: TVWRQCIPWUCNMI-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 6,7-dichloro-1H,2H,3H,5H-imidazolidino[2,1-b]quinazolin-2-one hydrochloride
• IUPAC Traditional name: anagrelide hydrochloride; agrylin hydrochloride
• Brand Name: Agrylin; Xagrid
• Synonyms: 6,7-Dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-one; BMY-26538-01; Agrylin; Tromboreductin; Xagrid; RL 603; Anagrelide Hydrochloride; Anagrelide HCL; Anagrelide Hydrochloride; BL-4162A; Anagrelide

Database IDs

• CAS Number: 58579-51-4; 68475-42-3
• PubChem SID: 160963609
• PubChem CID: 42786

CALCULATED PROPERTIES

• Acid pKa: 12.548792
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 1.9383392
• LogD (pH = 7.4): 1.9438572
• Log P: 1.9439309
• Molar Refractivity: 63.2506 cm^3
• Polarizability: 23.18002 Å^3
• Polar Surface Area: 44.7 Å^2
• Rotatable Bonds: 0
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: Acetone; DMSO; Ethanol; Very slightly soluble
• Apperance: Off-White to Pale Beige Solid
• Melting Point: >280°C (dec.)
• Hydrophobicity(logP): 2.4

Safety Information

• Storage Condition: -20°C Freezer

DETAILS

DrugBank - DB00261

• Drug Groups: approved
• Description: Anagrelide is a drug used for the treatment of essential thrombocytosis (ET; essential thrombocythemia). It also has been used in the treatment of chronic myeloid leukemia. [Wikipedia]
• Indication: For the treatment of patients with thrombocythemia, secondary to myeloproliferative disorders, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events.
• Pharmacology: Anagrelide is a drug used for the treatment of essential thrombocytosis (ET; essential thrombocythemia). It works by inhibiting the maturation of megakaryocytes into platelets. The exact mechanism of action is unclear, although it is known to be a potent (IC50 = 36nM) inhibitor of phosphodiesterase-III.
• Toxicity: There are no reports of overdosage with anagrelide, however thrombocytopenia, which can potentially cause bleeding, is expected from overdosage. Single oral doses of anagrelide at 2,500, 1,500 and 200 mg/kg in mice, rats and monkeys, respectively, were not lethal. Symptoms of acute toxicity were: decreased motor activity in mice and rats and softened stools and decreased appetite in monkeys.
• Affected Organisms: Humans and other mammals
• Biotransformation: Extensive, with < 1% recovered unchanged in the urine. Metabolized primarily in the liver by cytochrome P450 1A2 (CYP1A2). Recently, it was found that anagrelide is bio-transformed in humans into two major metabolites (6,7-dichloro-3-hydroxy-1,5 dihydro-imidazo[2,1-b]quinazolin-2-one (BCH24426) and 2-amino-5,6-dichloro-3,4,-dihydroquinazoline (RL603). Whether these metabolites have biological activities that may underlie the mode of action of the parent drug is presently unclear.
• Half Life: At fasting and at a dose of 0.5 mg of anagrelide, the plasma half-life is 1.3 hours.
• References: Voglova J, Maisnar V, Beranek M, Chrobak L: [Combination of imatinib and anagrelide in treatment of chronic myeloid leukemia in blastic phase] Vnitr Lek. 2006 Sep;52(9):819-22. [Pubmed] ; Petrides PE: Anagrelide: what was new in 2004 and 2005? Semin Thromb Hemost. 2006 Jun;32(4 Pt 2):399-408. [Pubmed] ; Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR: Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005 Jul 7;353(1):33-45. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Toronto Research Chemicals - A637300

A phosphodiesterase inhibitor with antiplatelet activity. Used as an antithrombocythemic.

REFERENCES

• Voglova J, Maisnar V, Beranek M, Chrobak L: [Combination of imatinib and anagrelide in treatment of chronic myeloid leukemia in blastic phase] Vnitr Lek. 2006 Sep;52(9):819-22. Pubmed
• Petrides PE: Anagrelide: what was new in 2004 and 2005? Semin Thromb Hemost. 2006 Jun;32(4 Pt 2):399-408. Pubmed
• Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR: Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005 Jul 7;353(1):33-45. Pubmed
• Fleming, J.S., et al.: Thromb. Res., 15, 373 (1979)
• Seiler, S., et al.: J. Pharmacol. Exp. Ther., 243, 767 (1979)
• Silverstein, M. N., et al.: N. Engl. J. Med., 318, 1292 (1979)
• Spencer, C.M., et al.: Drugs, 47, 809 (1979)