Cilostazol

Base Information

• Chemical Name: Cilostazol
• CAS No.: 73963-72-1
• Deprecated CAS: 89332-50-3
• Molecular Formula: C20H27N5O2
• Molecular Weight: 369.467
• Hs Code.: 29339900
• European Community (EC) Number: 689-122-9
• NSC Number: 758936
• UNII: N7Z035406B
• DSSTox Substance ID: DTXSID9045132
• Nikkaji Number: J23.223H
• Wikipedia: Cilostazol
• Wikidata: Q258591
• NCI Thesaurus Code: C1051
• RXCUI: 21107
• Pharos Ligand ID: 32SS3NCDZC7K
• Metabolomics Workbench ID: 43384
• ChEMBL ID: CHEMBL799
• Mol file: 73963-72-1.mol

Synonyms:6-(4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy)-3,4-dihydro-2(1H)-quinolinone;cilostazol;OPC 13013;OPC-13013;Pletal

Chemical Property of Cilostazol

Chemical Property:

• Appearance/Colour: off-white solid
• Vapor Pressure: 1.56E-17mmHg at 25°C
• Melting Point: 159-160 °C
• Refractive Index: 1.675
• Boiling Point: 664.7 °C at 760 mmHg
• PKA: 14.22±0.20(Predicted)
• Flash Point: 355.8 °C
• PSA: 81.93000
• Density: 1.34 g/cm³
• LogP: 3.60270
• Storage Temp.: Store at RT
• Solubility.: DMSO: 18 mg/mL, soluble
• XLogP3: 3.1
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 7
• Exact Mass: 369.21647512
• Heavy Atom Count: 27
• Complexity: 485

Purity/Quality:

99% ^*data from raw suppliers

Cilostazol ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Intermittent Claudication Agents
• Canonical SMILES: C1CCC(CC1)N2C(=NN=N2)CCCCOC3=CC4=C(C=C3)NC(=O)CC4
• Recent ClinicalTrials: Cilostazol and Methotrexate in Rheumatoid Arthritis
• Recent EU Clinical Trials: CILOSTAZOL AS IMATINIB SYNERGISER IN PATIENTS WITH UNRESECTABLE OR METASTATIC GIST TREATED BY GLIVEC?
• Recent NIPH Clinical Trials: Prevention of cerebral vasospasm following aneurysmal subarachnoid hemorrhage using cilostazol administration with combination enteral and parental nutrition therapy - randomized open-labeled multi-institutional prospective study
• Uses: It can significantly inhibit the platelet aggregation caused by various inducers and aggregates and can dissociate the aggregates without causing secondary aggregation. It has significant antithrombotic effect on the brain circulation and peripheral circulatory disturbance caused by collagen, ADP, arachidonic acid and sodium laurate. It can also be used for treating ischemic diseases such as chronic arterial occlusive ulcer, pain and coldness. An inhibitor of phosphodiesterase III 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
• Production method: Take 5-chloro-N-cyclohexyl pentanamide as the raw material. Under ice-cooling, to 15 mL of benzene solution containing 1.75g ??5-chloro-N-cyclohexyl-pentyl amide solution, slowly add 1.9 g of phosphorus pentachloride and stir at room temperature for 1h. At room temperature and stirring, add 1.4mol/L HN3 to 1 mL of the benzene solution. After stirring overnight, continue the reflux for 2h. The solvent was distilled off under reduced pressure with the residue being poured into ice water and subject to chloroform extraction. The extract was successively washed with water, dilute sodium bicarbonate solution and water, further dried by anhydrous sodium sulfate. After the chloroform was distilled off, the residue was subject to isopropanol-water recrystallization to obtain 1.7 g of 5-(4-chlorobutyl)-l-cyclohexyl-tetrazole, being as colorless needle-like crystals with the yield being 87% and the m.p. being 48-49 ℃. Dissolve 3.2 g 6-hydroxy-3, 4-dihydrogen-2(1H)-quinolinone and 1.4 g of potassium hydroxide in 20 mL of isopropanol. Under reflux, add drop wise of the isopropanol solution containing 5.7 g of the tetrazole obtained above. Continue stirring and reflux for 4h. Evaporate to dryness with the residue being extracted with chloroform. The extract was washed with l mol/L sodium hydroxide solution, dilute hydrochloric acid and water, dried by anhydrous sodium sulfate. Chloroform was distilled off with the residual liquid being subject to chromatograph on silica gel. Use chloroform-methanol (30: 1) for elution. Then apply methanol-water recrystallization to obtain 6.0 g of colorless needles cilostazol with the yield being 74% and the melting point being 158 ??~ 159 ℃.
• Description: Cilostazol is a platelet aggregation inhibitor with cerebral vasodilating activity, indicated for use in stroke and myocardial infarction. In patients with cerebral thrombosis, transient ischemia and cerebral arteriosclerosis, cilostazol significantly inhibits ADP-, collagenand epinephrine-induced platelet aggregation. Side effects include headache and tachycardia.
• Clinical Use: Cilostazol, a quinolinone derivative, is a potent orally active antiplatelet drug approved for the treatment of intermittent claudication (a peripheral artery disease resulting from blockage of blood vessels in the limbs).
• Drug interactions: Potentially hazardous interactions with other drugs Anagrelide: avoid concomitant use. Antibacterials: concentration increased by clarithromycin and erythromycin - consider reducing cilostazol dose. Antifungals: concentration possibly increased by ketoconazole and itraconazole - consider reducing cilostazol dose. Antivirals: concentration possibly increased by boceprevir, ritonavir and telaprevir - reduce cilostazol dose to 50 mg twice daily. Calcium-channel blockers: concentration increased by diltiazem - consider reducing cilostazol dose. Ulcer-healing drugs: concentration increased by omeprazole - consider reducing cilostazol dose.

Technology Process of Cilostazol

There total 13 articles about Cilostazol which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 98.7%

cilostazol bisulfate (877303-65-6) → 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydrocarbostyril (73963-72-1,89332-50-3)

Guidance literature:

With sodium hydroxide; In chloroform; water; Product distribution / selectivity;

Reference yield: 98.3%

→ 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydrocarbostyril (73963-72-1,89332-50-3)

Guidance literature:

Reference yield: 97.9%

cilostazol oxalate (877303-63-4) → 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydrocarbostyril (73963-72-1,89332-50-3)

Guidance literature:

With sodium hydroxide; In chloroform; water; Product distribution / selectivity;

upstream raw materials:

3,4-dihydro-6-hydroxy-2(1H)-quinolinone

1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole

cilostazol malate

cilostazol bisulfate

Downstream raw materials:

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

cilostazol malate

cilostazol oxalate

cilostazol bisulfate

Refernces

• 1、 -. "A preparation of cilostazol (by machine translation)". . . Retrieved 2019/06/13.
• 2、 -. "Preparation method of cilostazol". Paragraph 0039; 0041; 0043; 0045-0046; 0048-0049; 0051; 0058. . Retrieved 2018/01/03.