6-[4-(1-cyclohexyl-1H-1,2,3,4-tetrazol-5-yl)butoxy]-1,2,3,4-tetrahydroquinolin-2-one

• ChemBase ID: 1037
• Molecular Formular: C20H27N5O2
• Molecular Mass: 369.46068
• Monoisotopic Mass: 369.21647513
• SMILES: O(CCCCc1n(nnn1)C1CCCCC1)c1cc2CCC(=O)Nc2cc1
• Canonical SMILES: O=C1CCc2c(N1)ccc(c2)OCCCCc1nnnn1C1CCCCC1
• InChI: 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)
• InChIKey: RRGUKTPIGVIEKM-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 6-[4-(1-cyclohexyl-1H-1,2,3,4-tetrazol-5-yl)butoxy]-1,2,3,4-tetrahydroquinolin-2-one
• IUPAC Traditional name: pletal; cilostazol
• Brand Name: Pletaal; Pletal
• Synonyms: Cilostazolum [INN-Latin]; Cilostazole; Cilostazol; Pletal; Cilostazol; 6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)butoxy]-2-oxo-1,2,3,4-tetrahydroquinoline; 6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydroquinolin-2(1H)-one; 6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)-butoxy]-3,4-dihydro-2(1H)-quinolinone; OPC 13013; OPC 21; Pletaal; Cilostazol; 6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quinolinone; OPC-13013

Database IDs

• CAS Number: 73963-72-1
• MDL Number: MFCD00866780
• PubChem SID: 46506317; 24278291; 160964500
• PubChem CID: 2754
• CHEBI ID: 31401
• ATC CODE: B01AC23
• CHEMBL: 799
• Chemspider ID: 2652
• DrugBank ID: DB01166
• KEGG ID: D01896
• Unique Ingredient Identifier: N7Z035406B
• Wikipedia Title: Cilostazol
• Medline Plus: a601038

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.416321
• H Acceptors: 5
• H Donor: 1
• LogD (pH = 5.5): 3.3055658
• LogD (pH = 7.4): 3.305566
• Log P: 3.305566
• Molar Refractivity: 117.1349 cm^3
• Polarizability: 39.19583 Å^3
• Polar Surface Area: 81.93 Å^2
• Rotatable Bonds: 7
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.38
• LOG S: -4.06
• Solubility (Water): 3.24e-02 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; Dimethyl Sulfoxide; DMSO: soluble18 mg/mL; Ethanol; Methanol
• Apperance: off-white solid; White Solid
• Melting Point: 159-160°C
• Hydrophobicity(logP): 2.3

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• Storage Warning: Irritant
• RTECS: VC8277500
• German water hazard class: 2
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter

Pharmacology Properties

• Target: PDE
• Admin Routes: Oral
• Excretion: Renal
• Half Life: 11–13 hours
• Metabolism: Hepatic (CYP3A4- and CYP2C19-mediated)
• Protein Bound: 95–98%
• Pregnancy Category: C (US)
• Gene Information: human ... PDE3A(5139), PDE3B(5140)

Product Information

• Purity: >99% (HPLC)
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C20H27N5O2

DETAILS

DrugBank - DB01166

• Drug Groups: approved
• Description: Cilostazol is a medication used in the alleviation of the symptom of intermittent claudication in individuals with peripheral vascular disease. It is manufactured by Otsuka Pharmaceutical Co. under the trade name Pletal. Although drugs similar to cilostazol have increased the risk of death in patients with congestive heart failure, studies of significant size have not addressed people without the disease. [Wikipedia]
• Indication: For the reduction of symptoms of intermittent claudication (pain in the legs that occurs with walking and disappears with rest).
• Pharmacology: Cilostazol is a quinolinone derivative indicated for the reduction of symptoms of intermittent claudication, as indicated by an increased walking distance. Intermittent claudication is pain in the legs that occurs with walking and disappears with rest. The pain occurs due to reduced blood flow to the legs.
• Toxicity: Information on acute overdosage with cilostazol in humans is limited. The signs and symptoms of an acute overdose can be anticipated to be those of excessive pharmacologic effect: severe headache, diarrhea, hypotension, tachycardia, and possibly cardiac arrhythmias. The oral LD₅₀ of cilostazol is >5.0 g/kg in mice and rats and >2.0 g/kg in dogs.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Cilostazol is extensively metabolized by hepatic cytochrome P-450 enzymes, mainly 3A4, and, to a lesser extent, 2C19, with metabolites largely excreted in urine. Two metabolites are active, with one metabolite appearing to account for at least 50% of the pharmacologic (PDE III inhibition) activity after administration of cilostazol.
• Absorption: Cilostazol is absorbed after oral administration. A high fat meal increases absorption, with an approximately 90% increase in C_max and a 25% increase in AUC. Absolute bioavailability is not known.
• Half Life: 11-13 hours.
• Protein Binding: 95-98%
• Elimination: Cilostazol is extensively metabolized by hepatic cytochrome P-450 enzymes, mainly 3A4, and, to a lesser extent, 2C19, with metabolites largely excreted in urine. Cilostazol is eliminated predominately by metabolism and subsequent urinary excretion of metabolites. The primary route of elimination was via the urine (74%), with the remainder excreted in feces (20%). No measurable amount of unchanged cilostazol was excreted in the urine, and less than 2% of the dose was excreted as 3,4-dehydro-cilostazol.; About 30% of the dose was excreted in urine as 4'-trans-hydroxy-cilostazol.
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1294

Research Area: Cardiovascular Disease
Biological Activity:
Cilostazol is a medication used in the alleviation of the symptom of intermittent claudication in individuals with peripheral vascular disease. Cilostazol is a phosphodiesterase inhibitor with therapeutic focus on cAMP. It inhibits platelet aggregation and is a direct arterial vasodilator. Its main effects are dilation of the arteries supplying blood to the legs and decreasing platelet coagulation. [1]

Sigma Aldrich - C0737

Biochem/physiol Actions
Phosphodiesterase III (PDE3) inhibitor

Toronto Research Chemicals - C441500

A potent phosphodiesterase III A (PDE3A) inhibitor (IC50=0.2uM) and inhibitor of adenosine uptake. Has antimitogeni, antithrombotic, vasodilatory and cardiotonic properties in vivo. Also affects lipid levels in vivo.

REFERENCES

• http://en.wikipedia.org/wiki/Cilostazol
• Suri, A., et al.: J. Clin. Pharmacol., 38, 144 (1998)
• Park, S.-W., et al.: Am. J. Cardiol., 84, 511 (1998)
• Tsuchikane, E., et al.: Circulation, 100, 21 (1998)