Topiroxostat

Base Information

• Chemical Name: Topiroxostat
• CAS No.: 577778-58-6
• Molecular Formula: C13H8N6
• Molecular Weight: 248.247
• UNII: 0J877412JV
• DSSTox Substance ID: DTXSID80206462
• Nikkaji Number: J2.062.215F
• Wikipedia: Topiroxostat
• Wikidata: Q15725832
• NCI Thesaurus Code: C96311
• Pharos Ligand ID: UZMY4WQGNLGC
• Metabolomics Workbench ID: 146324
• ChEMBL ID: CHEMBL1078685
• Mol file: 577778-58-6.mol

Synonyms:4-(5-pyridin-4-yl-1H-(1,2,4) triazol-3-yl)pyridine-2-carbonitrile;FYX-051;topiroxostat

Chemical Property of Topiroxostat

Chemical Property:

• Boiling Point: 594.7±60.0 °C(Predicted)
• PKA: 7.47±0.10(Predicted)
• PSA: 91.14000
• Density: 1.45±0.1 g/cm3(Predicted)
• LogP: 1.80038
• XLogP3: 1.2
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 2
• Exact Mass: 248.08104428
• Heavy Atom Count: 19
• Complexity: 344

Purity/Quality:

99% ,99.9%, ^*data from raw suppliers

Topiroxostat ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1=CN=CC=C1C2=NC(=NN2)C3=CC(=NC=C3)C#N
• Recent ClinicalTrials: Study of FYU-981 in Hyperuricemia (Effect on Two Hyperuricemic Types)
• Recent NIPH Clinical Trials: Effect of topiroxostat on diabetic nephropathy in patients with type 2 diabetes mellitus
• Description: Topiroxostat is an orally-administered, non-purine, selective xanthine oxidase (XO) inhibitor developed for the treatment of hyperuricemia specifically for patients with gout in Japan. The drug was discovered and developed by Fuji Yakuhin. In contrast to conventional XO inhibitors such as febuxostat, topiroxostat interacts with key amino acid residues of the solvent channel.
• Uses: Topiroxostat is a selective xanthine oxidase inhibitor developed for treatment and management of hyperuricemia and gout. Xanthine oxidase, or xanthine oxidoreductase (XOR), regulates purine metabolism, and inhibition of the enzyme results in efficacious reduction of serum urate levels. Approved for therapeutic use in Japan since 2013, topiroxostat is marketed under the name Topiloric and Uriadec and is orally administered twice daily.
• Clinical Use: Topiroxostat, a novel XO inhibitor, ameliorated proteinuria in association with podocyte injury markers such as decrease in WT-1 and podocin expressions and foot process effacement on electron microscope.

Technology Process of Topiroxostat

There total 2 articles about Topiroxostat 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: 63.0%

pyridine-4-carbonitrile (100-48-1) + 2-Cyano-4-carbomethoxypyridine (94413-64-6) → 4-[3-(4-pyridinyl)-1H-1,2,4-triazol-5-yl]-2-pyridinecarbonitrile (577778-58-6)

Guidance literature:

2-Cyano-4-carbomethoxypyridine; With hydrazine hydrate; In ethanol; at 20 - 40 ℃; for 4h;

pyridine-4-carbonitrile; With sodium methylate; In ethanol; for 10.33h;

Reference yield:

2-Cyano-4-carbomethoxypyridine (94413-64-6) → [14C]-Topiroxostat (577778-58-6)

Guidance literature:

Multi-step reaction with 2 steps

1.1: hydrazine hydrate / ethanol / 3 h / -15 °C

2.1: sodium ethanolate / 1 h / 25 °C

2.2: 0.17 h / pH 5

2.3: 7 h / 80 °C / Reflux

With sodium ethanolate; hydrazine hydrate; In ethanol;

Reference yield: 87.1%

[14C]-Topiroxostat (577778-58-6) + toluene-4-sulfonic acid (104-15-4) → 4-[5-(pyridin-4-yl)-1H-1,2,4-triazol-3-yl]pyridine-2-carbonitrile p-toluenesulfonate (577778-88-2)

Guidance literature:

With sodium ethanolate; In 1,4-dioxane; water; at 35 - 40 ℃; for 1h; Solvent;

upstream raw materials:

pyridine-4-carbonitrile

2-Cyano-4-carbomethoxypyridine

Downstream raw materials:

4-[5-(pyridin-4-yl)-1H-1,2,4-triazol-3-yl]pyridine-2-carbonitrile p-toluenesulfonate

Refernces

• 1、 -. "Preparation method of topiroxostat". . . Retrieved 2018/03/26.