Istradefylline

Base Information

• Chemical Name: Istradefylline
• CAS No.: 155270-99-8
• Molecular Formula: C20H24N4O4
• Molecular Weight: 384.435
• European Community (EC) Number: 803-302-8
• UNII: 2GZ0LIK7T4
• DSSTox Substance ID: DTXSID7057652
• Nikkaji Number: J1.018.438J,J2.888.328E
• Wikipedia: Istradefylline
• Wikidata: Q905783
• NCI Thesaurus Code: C73268
• RXCUI: 2199015
• Pharos Ligand ID: G168UKNUG9TX
• Metabolomics Workbench ID: 152859
• ChEMBL ID: CHEMBL431770
• Mol file: 155270-99-8.mol

Synonyms:8-(2-(3,4-dimethoxyphenyl)ethenyl)-1,3-diethyl-3,7-dihydro-7-methyl-1H-purine-2,6-dione;istradefylline;KW 6002;KW-6002;KW6002

Chemical Property of Istradefylline

Chemical Property:

• Vapor Pressure: 2.12E-14mmHg at 25°C
• Melting Point: 191 °C
• Refractive Index: 1.598
• Boiling Point: 600.991 °C at 760 mmHg
• PKA: 0.47±0.70(Predicted)
• Flash Point: 317.268 °C
• PSA: 80.28000
• Density: 1.243 g/cm³
• LogP: 2.12410
• Storage Temp.: 2-8°C
• Solubility.: DMSO: soluble5mg/mL (clear solution)
• XLogP3: 2.5
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 6
• Exact Mass: 384.17975526
• Heavy Atom Count: 28
• Complexity: 613

Purity/Quality:

99%up ^*data from raw suppliers

Istradefylline ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 25
• Safety Statements: 45

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Central Nervous System Agents
• Canonical SMILES: CCN1C2=C(C(=O)N(C1=O)CC)N(C(=N2)C=CC3=CC(=C(C=C3)OC)OC)C
• Isomeric SMILES: CCN1C2=C(C(=O)N(C1=O)CC)N(C(=N2)/C=C/C3=CC(=C(C=C3)OC)OC)C
• Recent ClinicalTrials: Combining Low Oxygen Therapy and an Adenosine A2a Receptor Antagonist to Improve Functional Mobility After Spinal Cord Injury
• Recent EU Clinical Trials: A Phase 3, Long-term, Open-label Study of Istradefylline in
• Recent NIPH Clinical Trials: A study on improvement of cognitive function by istradefylline for parkinson disease
• Description: In March 2013, istradefylline (also known as KW-6002) was approved in Japan for adjunctive treatment of Parkinson’s disease (PD). Istradefylline acts by antagonism of the adenosine A2A receptor, which is colocalized with dopamine D2 receptors in the striatum, to enhance dopamine D2-dependent signaling. Istradefylline is a light-sensitive compound and has been evaluated in vitro under low-light conditions to prevent isomerization of the (E)-styryl group and decomposition. Istradefylline has a Ki of 2.2 nM for the rat adenosine A2A receptor and an ED50 of 0.03 mg/kg, po, in reversal of haloperidol-induced catalepsy in mice. Further characterization showed istradefylline to have a Ki of 12 nM for the human adenosine A2A receptor, to be highly selective, and to be a functional competitive antagonist. Istradefylline has activity alone and in combination with levo-dopa in preclinical animal models of PD. The synthesis of istradefylline was accomplished by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-mediated coupling of 5,6-diamino-1,3-diethyluracil with 3,4-dimethoxycinnamic acid, followed by cyclization upon treatment with aqueous NaOH, and selective methylation (MeI, K2CO3, and DMF). Istradefylline is an adenosine receptor 2A (A2A) antagonist (Ki = 2.2 nM in a radioligand binding assay). In vivo, istradefylline inhibits catalepsy induced by haloperidol with an ED50 value of 0.23 mg/kg in rats. Oral administration of istradefylline alleviates postural defects in a dose-dependent manner without inducing dyskinesias or hyperactivity in an MPTP-induced marmoset model of Parkinson''s disease. It also decreases bradykinesias induced by L-DOPA and improves attentional and working memory deficits in an MPTP-induced macaque model of Parkinson''s disease. Formulations containing istradefylline are used to extend on-time in Parkinson''s disease patients experiencing motor fluctuations.
• Uses: Treatment of Parkinson’s disease (adenosine A 2A receptor antagonist).

Technology Process of Istradefylline

There total 22 articles about Istradefylline 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: 95.0%

1,3-diethyl-7-methyl-1H-purine-2,6(3H,7H)-dione (31617-39-7) + 3,4-dimethoxystyrene (6380-23-0) → istradefylline (155270-99-8,606080-73-3)

Guidance literature:

1,3-diethyl-7-methyl-1H-purine-2,6(3H,7H)-dione; With pyridine; palladium diacetate; copper(II) acetate monohydrate; copper(l) chloride; In N,N-dimethyl acetamide; at 20 ℃; for 0.0833333h; Inert atmosphere;

3,4-dimethoxystyrene; In N,N-dimethyl acetamide; at 120 ℃; for 20h; Inert atmosphere;

DOI:10.1039/c2cc17557f

Reference yield: 94.0%

C20H26N4O5 → istradefylline (155270-99-8,606080-73-3)

Guidance literature:

With sodium methylate; In 1,4-dioxane; at 90 - 95 ℃; for 3h; Reagent/catalyst; Temperature;

Reference yield: 92.5%

methyl 2‐cyano‐2‐[(2E)‐3‐(3,4‐dimethoxyphenyl)‐N‐methylprop‐2‐enamido]acetate → istradefylline (155270-99-8,606080-73-3)

Guidance literature:

With N,N'-diethylurea; In 1,4-dioxane; at 90 - 95 ℃; for 4h;

upstream raw materials:

8-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-1,3-diethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione

methyl iodide

5,6-diamino-1,3-diethyluracil

6-amino-1,3-diethyl-5-nitroso-1H,3H-pyrimidine-2,4-dione

Downstream raw materials:

(E)-8-(3,4-Dihydroxystyryl)-1,3-diethyl-7-methylxanthine

(Z)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methylxanthine

Refernces

• 1、 -. "Environment-friendly preparation method of istradefylline". . . Retrieved 2019/08/02.
• 2、 -. "Improved synthesis technology of istradefylline". . . Retrieved 2018/04/28.