ANAGRELIDE HYDROCHLORIDE ANHYDROUS

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H7Cl2N3O.ClH
Molecular Weight	292.549
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of ANAGRELIDE HYDROCHLORIDE ANHYDROUS

Structure Search

SMILES

Cl.ClC1=CC=C2NC3=NC(=O)CN3CC2=C1Cl

InChI

InChIKey=TVWRQCIPWUCNMI-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C10H7Cl2N3O
Molecular Weight	256.088
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020333s017lbl.pdf
Curator's Comment: description was created based on several sources, including: http://www.rxlist.com/agrylin-drug.htm | https://www.drugs.com/pro/anagrelide.html | https://www.ncbi.nlm.nih.gov/pubmed/20331456

Anagrelide is an orally active quinazinolone derivative that was originally developed as an antiplatelet drug. The drug inhibits cyclic nucleotide phosphodiesterase III (PDEIII) and phopholipase A2, which is thought to cause the side effects of vasodilation, positive inotropism, reduced platelet aggregation. However, significant inhibition of platelet aggregation is observed only at doses of anagrelide higher than those required to reduce platelet count. It is indicated for the treatment of patients with thrombocythemia, secondary to myeloproliferative disorders. Commonly reported side effects of anagrelide include: abdominal pain, dizziness, headache, nausea, and palpitations. Other side effects include: back pain, fever, tachycardia, vomiting, and anorexia. There is a single case report, which suggests that sucralfate may interfere with anagrelide absorption. Anagrelide is an inhibitor of cyclic AMP PDE III. The effects of medicinal products with similar properties such as inotropes milrinone, enoximone, amrinone, olprinone and cilostazol may be exacerbated by anagrelide.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Phosphodiesterase 3 60 Target ID: CHEMBL2094125 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16041400 \| https://www.ncbi.nlm.nih.gov/pubmed/20331456 \| https://www.ncbi.nlm.nih.gov/pubmed/2456068	Inhibitor 8297	36.0 nM [IC50]
Phopholipase A2 3 Target ID: Phopholipase A2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20331456	Inhibitor 8297
Cytochrome P450 1A2 72 Target ID: P05177 Gene ID: 1544.0 Gene Symbol: CYP1A2 Target Organism: Homo sapiens (Human) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020333s017lbl.pdf	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Thrombocythemia 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020333s017lbl.pdf	Primary		Approved 8429	AGRYLIN Approved Use Anagrelide hydrochloride capsules are indicated 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 (see CLINICAL STUDIES, DOSAGE AND ADMINISTRATION). Launch Date 1997

C_max

Value	Dose	Co-administered	Analyte	Population
10.28 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19302911	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		ANAGRELIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
28.39 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19302911	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		ANAGRELIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.38 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19302911	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		ANAGRELIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
1.9 mg 1 times / day multiple, oral (mean) Recommended Dose: 1.9 mg, 1 times / day Route: oral Route: multiple Dose: 1.9 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10200810 Page: p.33	unhealthy, 58 n = 16 Health Status: unhealthy Condition: Thrombocythemia Age Group: 58 Sex: M+F Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/10200810 Page: p.33	Disc. AE: Dizziness postural, Palpitations... AEs leading to discontinuation/dose reduction: Dizziness postural (6.25%) Palpitations (12.5%) Chest pain (6.25%) Sinus tachycardia (6.25%) Abdominal pain (6.25%) Sources: https://pubmed.ncbi.nlm.nih.gov/10200810 Page: p.33
1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020333s024lbl.pdf Page: p.4	unhealthy n = 942 Health Status: unhealthy Condition: Thrombocythemia Population Size: 942 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020333s024lbl.pdf Page: p.4	Disc. AE: Headache, Diarrhea... AEs leading to discontinuation/dose reduction: Headache Diarrhea Edema Palpitations Abdominal pain Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020333s024lbl.pdf Page: p.4
10 mg 1 times / day multiple, oral (total daily dose) Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020333s024lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Thrombocythemia Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020333s024lbl.pdf Page: p.1	Disc. AE: Cardiotoxicity, QT interval prolonged... AEs leading to discontinuation/dose reduction: Cardiotoxicity QT interval prolonged Ventricular tachycardia Pulmonary hypertension Bleeding Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020333s024lbl.pdf Page: p.1

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:142290	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:142290
ChemicalBook	CB8246866	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8246866
MolPort	MolPort-003-844-624	https://www.molport.com/shop/molecule-link/MolPort-003-844-624
MolPort	MolPort-005-934-314	https://www.molport.com/shop/molecule-link/MolPort-005-934-314
ZINC	ZINC000003871541	http://zinc15.docking.org/substances/ZINC000003871541
eMolecules	2726176	https://www.emolecules.com/cgi-bin/more?vid=2726176
eMolecules	901387	https://www.emolecules.com/cgi-bin/more?vid=901387

PubMed

Title	Date	PubMed
3,4-Dihydroquinolin-2(1H)-ones as combined inhibitors of thromboxane A2 synthase and cAMP phosphodiesterase.	1992 Feb 21	1311763
Inhibitors of blood platelet cAMP phosphodiesterase. 2. Structure-activity relationships associated with 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-ones substituted with functionalized side chains.	1992 Jul 10	1321910
Anagrelide metabolite induces thrombocytopenia in mice by inhibiting megakaryocyte maturation without inducing platelet aggregation.	2001 Dec	11750100
Unexplained pulmonary hypertension in chronic myeloproliferative disorders.	2001 Sep	11555513
[Treatment of essential thrombocythemia with anagrelide: a ten-year experience].	2002	12150005
What is the standard treatment in essential thrombocythemia.	2002 Aug	12430943
Essential thrombocythemia (ET): moving from palliation to cure.	2002 Dec	12475736
Essential thrombocythemia: diagnosis and treatment, with special emphasis on the use of anagrelide.	2002 Jun	12243981
Variation of PDGF, TGFbeta, and bFGF levels in essential thrombocythemia patients treated with anagrelide.	2002 Jun	12111780
Other secondary sequelae of treatments for myeloproliferative disorders.	2002 Jun	12096354
Therapeutic options for essential thrombocythemia and polycythemia vera.	2002 Jun	12096352
Comparison of the pharmacological mechanisms involved in the platelet lowering actions of anagrelide and hydroxyurea: a review.	2002 Nov	12487784
[Anagrelide-induced changes of megakaryopoiesis during therapy of chronic myeloproliferative disorders with thrombocythemia].	2002 Nov	12436295
Associated thrombophilic defects in essential thrombocythaemia: their relationship with clinical manifestations.	2003	14967408
Portal vein thrombosis after laparoscopy-assisted splenectomy and cholecystectomy.	2003 Apr	12677588
[Ulcers on the legs and feet: a seldom recognised side effect of hydroxyurea].	2003 Aug 2	12924084
[Recurring ischemic cerebral infarction caused by primary thrombocytosis in infancy].	2003 Dec 1-15	14669144
Indications for lowering platelet numbers in essential thrombocythemia.	2003 Jan	12682878
Pilot study of pegylated interferon-alpha 2b in patients with essential thrombocythemia.	2003 Jan	12497210
Treatment of essential thrombocythemia in childhood.	2003 Jul-Aug	12775533
Treatment indications and choice of a platelet-lowering agent in essential thrombocythemia.	2003 May	12901347
Efficacy and safety of long-term use of hydroxyurea in young patients with essential thrombocythemia and a high risk of thrombosis.	2003 May 1	12707224
Essential thrombocytosis: diagnostic and treatment dilemmas.	2003 Nov-Dec	14750750
Pharmacotherapy of essential thrombocythaemia: economic considerations.	2003 Sep	12943479
Severe hypersensitivity pneumonitis associated with anagrelide.	2003 Sep	12921504
Management of the myeloproliferative disorders : distinguishing data from dogma.	2004	15190294
Treatment paradigms in the management of myeloproliferative disorders.	2004 Apr	15190519
The leukemia controversy in myeloproliferative disorders: is it a natural progression of disease, a secondary sequela of therapy, or a combination of both?	2004 Apr	15190518
Anagrelide: an update on its mechanisms of action and therapeutic potential.	2004 Aug	15270658
[Anagrelide in the treatment of thrombocythemia essential (ET)].	2004 Dec	15962609
Thrombocytosis in an infant with high thrombopoietin concentrations.	2004 Feb	14767209
Thalidomide for the treatment of idiopathic myelofibrosis.	2004 Jan	14962263
Thrombocytosis.	2004 Jun 10	15190151
Essential thrombocythaemia in children: is a treatment needed?	2004 May	15155103
Adverse effects and benefits of two years of anagrelide treatment for thrombocythemia in chronic myeloproliferative disorders.	2004 May	15136214
Essential thrombocythemia-related acute ST-segment elevation myocardial infarction. A case report and literature review.	2004 May-Jun	15156266
Anagrelide therapy in pregnancy: report of a case of essential thrombocythemia.	2004 Nov	15278298
Anagrelide for thrombocytosis in myeloproliferative disorders: a prospective study to assess efficacy and adverse event profile.	2004 Nov 15	15476273
Current treatment of myelofibrosis.	2005 Apr	16166999
Anagrelide is effective in treating patients with hydroxyurea-resistant thrombocytosis in patients with chronic myeloid leukemia.	2005 Jan	15510207
Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia.	2005 Jul 7	16000354
Myeloproliferative disorders.	2005 Jul-Aug	16138485
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Anagrelide: analysis of long-term efficacy, safety and leukemogenic potential in myeloproliferative disorders.	2005 May	15755500
Renal tubular injury associated with anagrelide use.	2005 May	15728271
Anagrelide does not exert a myelodysplastic effect on megakaryopoiesis: a comparative immunohistochemical and morphometric study with hydroxyurea.	2005 Oct	16136489
Comparison of the biological activities of anagrelide and its major metabolites in haematopoietic cell cultures.	2005 Oct	16041400
Successful outcome with anagrelide in pregnancy.	2005 Oct	15959777
Treatment of symptomatic patients with essential thrombocythemia: effectiveness of anagrelide.	2005 Sep	16138352
Risk-adapted therapy in essential thrombocythemia and polycythemia vera.	2005 Sep	15963833

Patents

Sample Use Guides

In Vivo Use Guide

0.5 mg qid or 1 mg bid (2 capsules of 0.5 mg twice a day) for at least one week

Route of Administration: Oral

In Vitro Use Guide

Anagrelide was studied as an inhibitor of PDE fractions I, II and III separated from each other from rabbit heart supernatant. Anagrelide did not inhibit PDE I or II except at a concentration of 10(-4) M where inhibition of 33 and 39%, respectively, was noted. As expected, anagrelide inhibited PDE fraction III with a dose-response curve that was closely similar to that seen in the human platelet preparation. The IC50 for inhibition of the rabbit heart PDE fraction III was 7 x 10(-8) M.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:23:30 GMT 2023` Edited by `admin` on `Fri Dec 15 15:23:30 GMT 2023`
Record UNII	VNS4435G39
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ANAGRELIDE HYDROCHLORIDE ANHYDROUS

Common Name

English

6,7-DICHLORO-1,5-DIHYDROIMIDAZO(2,1-.BETA.)-QUINAZOLIN-2(3H)-ONE MONOHYDROCHLORIDE

Common Name

English

NSC-759170

Code

English

ANAGRELIDE HCL

Common Name

English

ANAGRELIDE HYDROCHLORIDE [VANDF]

Common Name

English

NSC-724577

Code

English

ANAGRELIDE HYDROCHLORIDE [USAN]

Common Name

English

Anagrelide hydrochloride [WHO-DD]

Common Name

English

IMIDAZO(2,1-.BETA.)QUINAZOLIN-2(3H)-ONE, 6,7-DICHLORO-1,5-DIHYDRO-, MONOHYDROCHLORIDE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1327