CILOSTAZOL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H27N5O2
Molecular Weight	369.4607
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C1CCC2=CC(OCCCCC3=NN=NN3C4CCCCC4)=CC=C2N1

InChI

InChIKey=RRGUKTPIGVIEKM-UHFFFAOYSA-N

InChI=1S/C20H27N5O2/c26-20-12-9-15-14-17(10-11-18(15)21-20)27-13-5-4-8-19-22-23-24-25(19)16-6-2-1-3-7-16/h10-11,14,16H,1-9,12-13H2,(H,21,26)

HIDE SMILES / InChI

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=146824
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/11830753

Cilostazol is a PDE3 inhibitor which is used for the treatment of intermittent claudication. The drug positively affects the platelet aggregation and may be used off-label as a measure to prevent coronary thrombosis/restenosis and stroke recurrence.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Phosphodiesterase 3 60 Target ID: CHEMBL2094125 Sources: https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=146824	Inhibitor 8297		0.57 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Intermittent claudication 12 Sources: https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=146824	Palliative		Approved 8429	CILOSTAZOL Approved Use Cilostazol tablets are indicated for the reduction of symptoms of intermittent claudication, as indicated by an increased walking distance. Launch Date 2004

C_max

Value	Dose	Co-administered	Analyte	Population
701 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31372190	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		CILOSTAZOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
9.2 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21718207	0.5 mg/kg single, oral dose: 0.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		CILOSTAZOL serum	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
13724 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31372190	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		CILOSTAZOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
17.5 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21718207	0.5 mg/kg single, oral dose: 0.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		CILOSTAZOL serum	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
13.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31372190	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		CILOSTAZOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
58.7% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21718207	0.5 mg/kg single, oral dose: 0.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		CILOSTAZOL serum	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/020863s011lbl.pdf			CILOSTAZOL plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:31401	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:31401
ChemicalBook	CB2362876	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2362876
MolPort	MolPort-001-758-007	https://www.molport.com/shop/molecule-link/MolPort-001-758-007
Selleck Chemicals	Cilostazol	http://www.selleckchem.com/products/Cilostazol.html
ZINC	ZINC000001552174	http://zinc15.docking.org/substances/ZINC000001552174
eMolecules	27518122	https://www.emolecules.com/cgi-bin/more?vid=27518122
eMolecules	535670	https://www.emolecules.com/cgi-bin/more?vid=535670

PubMed

Title	Date	PubMed
Three cases of digital ischemia successfully treated with cilostazol.	2001 Nov	11958391
Pharmacologic treatment for intermittent claudication.	2002	12710846
Cilostazol treatment of claudication in diabetic patients.	2002	12564659
Rapid ventricular tachycardias associated with cilostazol use.	2002	12075874
Pharmacokinetic and pharmacodynamic modeling of the antiplatelet and cardiovascular effects of cilostazol in healthy humans.	2002 Apr	11956507
Randomized comparison of cilostazol versus ticlopidine hydrochloride for antiplatelet therapy after coronary stent implantation for prevention of late restenosis.	2002 Aug	12177649
Polymorphic forms of cilostazol.	2002 Aug	12154319
Can claudication be improved with medication?	2002 Dec	12478498
Effect of cilostazol on treadmill walking, community-based walking ability, and health-related quality of life in patients with intermittent claudication due to peripheral arterial disease: meta-analysis of six randomized controlled trials.	2002 Dec	12473004
Pharmacologic therapy for peripheral arterial disease and claudication.	2002 Dec	12469066
Spontaneous recanalization of arterial occlusions: an unusual mechanism for symptomatic improvement.	2002 Dec	12469047
Clinical manifestation of atherosclerotic peripheral arterial disease and the role of cilostazol in treatment of intermittent claudication.	2002 Dec	12463722
Thermally-prepared polymorphic forms of cilostazol.	2002 Dec	12434391
Modulation of the erythropoietin-induced proliferative pathway by cAMP in vascular smooth muscle cells.	2002 Dec	12419709
Meta-analysis of results from eight randomized, placebo-controlled trials on the effect of cilostazol on patients with intermittent claudication.	2002 Dec 15	12480040
A phosphodiesterase inhibitor, cilostazol, prevents the onset of silent brain infarction in Japanese subjects with Type II diabetes.	2002 Feb	11935149
Cilostazol.	2002 Feb 1	11862634
[Etiology, pathogenesis and management of senile inflammatory pulmonary diseases].	2002 Jan	11925914
Prevention of ventricular fibrillation by cilostazol, an oral phosphodiesterase inhibitor, in a patient with Brugada syndrome.	2002 Jul	12139296
Potential emerging therapeutic strategies to prevent restenosis in the peripheral vasculature.	2002 Jul	12112901
Cilostazol enhances IL-1beta-induced NO production and apoptosis in rat vascular smooth muscle via PKA-dependent pathway.	2002 Jul	11955955
Peripheral arterial disease.	2002 Jun	12230639
[Antiproliferative coated stents and intracoronary brachytherapy: common traits and differences].	2002 Jun	12219692
[Effect of cilostazol on adhesion molecules of STZ-induced diabetic rats].	2002 Jun 10	12126539
Treating peripheral arterial disease in patients with diabetes.	2002 Mar	12180355
Evidence-based symptom relief of intermittent claudication: efficacy and safety of cilostazol.	2002 Mar	12180354
The pharmacology of cilostazol.	2002 Mar	12180353
Recent advances in antiplatelet agents.	2002 Mar	11945125
Effects of a single oral dose of cilostazol on epicardial coronary arteries and hemodynamics in humans.	2002 Mar	11922271
Measuring treatment effects of cilostazol on clinical trial endpoints in patients with intermittent claudication.	2002 Mar	11892686
The herbal medicine Dai-kenchu-to and one of its active components [6]-shogaol increase intestinal blood flow in rats.	2002 Mar 15	12148698
Effect of cilostazol in patients with intermittent claudication: a randomized, double-blind, placebo-controlled study.	2002 Mar-Apr	11951094
A rational approach to diagnosis and treatment of intermittent claudication.	2002 May	12018666
Management of patients with intermittent claudication.	2002 Nov	12469984
Pharmacotherapy for peripheral arterial disease: emerging therapeutic options.	2002 Nov-Dec	12463615
Effects of cilostazol, a selective cyclic AMP phosphodiesterase inhibitor on isolated rabbit spinal arterioles.	2002 Oct	12533252
Cilostazol, a potent phosphodiesterase type III inhibitor, selectively increases antiatherogenic high-density lipoprotein subclass LpA-I and improves postprandial lipemia in patients with type 2 diabetes mellitus.	2002 Oct	12370857
New mechanism of action for cilostazol: interplay between adenosine and cilostazol in inhibiting platelet activation.	2002 Oct	12352320
Comparison of the effects of cilostazol and milrinone on cAMP-PDE activity, intracellular cAMP and calcium in the heart.	2002 Sep	12652111
[State of treatment of coronary artery disease by drug releasing stents].	2002 Sep	12378395
Identification of interaction sites of cyclic nucleotide phosphodiesterase type 3A with milrinone and cilostazol using molecular modeling and site-directed mutagenesis.	2002 Sep	12181427
Debulking and stenting versus debulking only of coronary artery disease in patients treated with cilostazol (final results of ESPRIT).	2002 Sep 15	12231079
Failure of pentoxifylline or cilostazol to improve blood and plasma viscosity, fibrinogen, and erythrocyte deformability in claudication.	2002 Sep-Oct	12365857
Pharmacotherapy as adjunctive treatment for serious foot wounds in the patient with diabetes: a case study.	2003 Apr	12732740
Effect of cilostazol on the ventricular escape rate and neurohumoral factors in patients with third-degree atrioventricular block.	2003 Apr	12684307
Cilostazol: an "intermittent claudication" remedy for the management of third-degree AV block.	2003 Apr	12684279
A paclitaxel-eluting stent for the prevention of coronary restenosis.	2003 Apr 17	12700373
Effects of cilostazol on serum lipid concentrations and plasma fatty acid composition in type 2 diabetic patients with peripheral vascular disease.	2003 Feb	12624709
Inhibitory action of cilostazol, a phosphodiesterase III inhibitor, on catecholamine secretion from cultured bovine adrenal chromaffin cells.	2003 Jan	12688393
Adenosine receptors and phosphodiesterase inhibitors stimulate Cl- secretion in Calu-3 cells.	2003 Sep	12714375

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage of cilostazol tablets is 100 mg b.i.d. taken at least half an hour before or 2 hours after breakfast and dinner.

Route of Administration: Oral

In Vitro Use Guide

In vitro assay of anti-platelet effects of cilostazol against collagen-induced aggregation using Multiplate produced a graded dose-dependent inhibition curve with IC50 value of 75.4 ± 2.4 uM while it showed a highly sensitive and all-or-none type inhibition response from 25 uM in PFA-100.

Name

Type

Language

CILOSTAZOL

Official Name

English

6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydrocarbostyril

Common Name

English

CILOSTAZOL [MI]

Common Name

English

OPC-21

Code

English

2(1H)-QUINOLINONE, 6-(4-(1-CYCLOHEXYL-1H-TETRAZOL-5-YL)BUTOXY)-3,4-DIHYDRO-

Systematic Name

English

CILOSTAZOL [USP-RS]

Common Name

English

NSC-758936

Code

English

CILOSTAZOL [JAN]

Common Name

English

Cilostazol [WHO-DD]

Common Name

English

OPC-13013

Code

English

CILOSTAZOL [VANDF]

Common Name

English

CILOSTAZOL [USAN]

Common Name

English

PLETAL

Brand Name

English

CILOSTAZOL [MART.]

Common Name

English

CILOSTAZOL [USP MONOGRAPH]

Common Name

English

cilostazol [INN]

Common Name

English

CILOSTAZOL [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C744