Pirfenidone

Base Information

• Chemical Name: Pirfenidone
• CAS No.: 53179-13-8
• Molecular Formula: C12H11NO
• Molecular Weight: 185.225
• Hs Code.: 29337900
• European Community (EC) Number: 621-260-7
• NSC Number: 748456
• UNII: D7NLD2JX7U
• DSSTox Substance ID: DTXSID4045183
• Nikkaji Number: J10.084F
• Wikipedia: Pirfenidone
• Wikidata: Q2060696
• NCI Thesaurus Code: C2635
• RXCUI: 1592254
• Metabolomics Workbench ID: 149350
• ChEMBL ID: CHEMBL1256391
• Mol file: 53179-13-8.mol

Synonyms:1-phenyl-5-(trideuteriomethyl)-1,2-dihydropyridin-2-one;5-methyl-1-phenyl-2-(1H)-pyridone;Deskar;deupirfenidone;esbriet;pirfenidone

Chemical Property of Pirfenidone

Chemical Property:

• Appearance/Colour: Off-white solid
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 96-97 °C
• Refractive Index: 1.592
• Boiling Point: 329.075 °C at 760 mmHg
• PKA: -0.16±0.63(Predicted)
• Flash Point: 152.741 °C
• PSA: 22.00000
• Density: 1.138 g/cm³
• LogP: 2.14590
• Storage Temp.: Store at RT
• Solubility.: DMSO: ≥10 mg/mL, soluble
• XLogP3: 1.9
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 1
• Exact Mass: 185.084063974
• Heavy Atom Count: 14
• Complexity: 285

Purity/Quality:

99.0% Min., ^*data from raw suppliers

Pirfenidone ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 36-24/25

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Pulmonary Fibrosis Agents
• Canonical SMILES: CC1=CN(C(=O)C=C1)C2=CC=CC=C2
• Recent ClinicalTrials: Targeting Residual Activity By Precision, Biomarker-Guided Combination Therapies of Multiple Sclerosis (TRAP-MS)
• Recent EU Clinical Trials: Assessment of the effect of Wharton's jelly mesenchymal stem cell
• Recent NIPH Clinical Trials: A Phase 2 Study to Evaluate Dose-Response of TAS-115 in Patients with Chronic Fibrosing Interstitial Lung Diseases with a Progressive Phenotype
• Physical properties: Pirfenidone is a white to pale yellow, non-hygroscopic powder. It is more soluble in methanol, ethyl alcohol, acetone and chloroform than in water and 1.0 N HCl. The melting point is approximately 109°C.
• Uses: Pirfenidone is a broad-spectrum antifibrotic drug that modulates diverse cytokine action involving TGF-β, TNF-α, epidermal growth factor, platelet-derived growth factor,vascular endothelial growth factor, insulin-like growth factor 1, fibroblast growth factor, and others.Pirfenidone has been effective in the prevention and regression of pulmonary fibrosis, peritoneal sclerosis, hepatic cirrhosis, uterine fibromyoma, and other scarring and fibrotic conditions. It doesn’t cure the condition or reverse any existing scarring but it can effectively slow down the rate of lung function decline by about 50%. In the UK, Pirfenidone is currently only approved for treating IPF, and not for other forms of pulmonary fibrosis. Pirfenidone has been used:as a post-operative eye drop in rabbits to analyse its antifibrotic effect to improve glaucoma filtration surgeryas an anti-scarring agent to examine whether it affects the foreign body reaction after glaucoma drainage device (GDD) implantation in a rabbitto test its antifibrotic potential in primary cultures of human orbital fibroblasts (hOFs)as tumor necrosis factor (TNFα) inhibitor to study its effect in hypoxia Pirfenidone is in a group of medicines called antifibrotic agents. Pirfenidone has demonstrated activity in multiple fibrotic conditions, including those of the lung, kidney and liver. It affects your body’s immune system and reduces the amount of fibrosis (scarring) in the lungs. Pirfenidone is one of two medicines that are approved in Canada to treat Idiopathic Pulmonary Fibrosis (IPF). Another name for this medicine is Esbriet.
• Description: Until recently, IPF therapy consisted of a combination of corticosteroids and immunosuppressive agents (azathioprine and cyclophosphamide) to target the inflammation that was believed to be the pathogenic stimulus.Since IPF is now considered to be predominantly a disorder of fibroproliferation, agents that intervene in fibrogenesis have moved to the forefront of treatment options. With demonstrated efficacy in a bleomycin-induced lung fibrosis animal model, pirfenidone has been developed and launched as an approved therapy for IPF. Its antifibrotic activity is derived from the inhibition of p38 MAP kinase that is upstream of transforming growth factor-β (TGF-β), a cytokine implicated in the stimulation of collagen synthesis and the inhibition of its degradation. Pirfenidone also inhibits the expression of TNF-α, IL-1, and ICAM-1, so it possesses the dual benefit of an anti-inflammatory and antifibrotic agent. This relatively simplistic drug is constructed by the copper-catalyzed reaction of 5-methyl-2(1H)-pyridinone with bromo- or chlorobenzene. .

Technology Process of Pirfenidone

There total 49 articles about Pirfenidone 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: 98.0%

5-methyl-2-pyridone (1003-68-5) + triphenylbismuthane (603-33-8) → Pirfenidone (53179-13-8)

Guidance literature:

With pyridine; copper diacetate; In dichloromethane; at 50 ℃; for 16h; Reagent/catalyst;

DOI:10.1002/chem.201303684

Reference yield: 93.6%

2-pentenenitrile (13284-42-9) + orthoformic acid triethyl ester (122-51-0) + aniline (62-53-3) → Pirfenidone (53179-13-8)

Guidance literature:

2-pentenenitrile; orthoformic acid triethyl ester; With toluene-4-sulfonic acid; In N,N-dimethyl-formamide; at 100 - 105 ℃; for 4h;

aniline; In N,N-dimethyl-formamide; at 80 - 100 ℃; for 3h;

With water; In N,N-dimethyl-formamide; at 20 ℃; for 2h;

Reference yield: 92.7%

2-pentenenitrile (13284-42-9) + aniline (62-53-3) + trimethyl orthoformate (149-73-5) → Pirfenidone (53179-13-8)

Guidance literature:

2-pentenenitrile; trimethyl orthoformate; With toluene-4-sulfonic acid; In N,N-dimethyl-formamide; at 90 - 100 ℃; for 4h;

aniline; In N,N-dimethyl-formamide; at 80 - 95 ℃; for 3h;

With water; In N,N-dimethyl-formamide; at 20 ℃; for 2h; Reagent/catalyst; Temperature; Solvent;

upstream raw materials:

5-methyl-2-pyridone

iodobenzene

copper

1-bromo-4-methoxy-benzene

Downstream raw materials:

5-bromomethyl-1-phenylpyridine-2(1H)-one

1-phenyl-5-((o-tolylamino)methyl)pyridin-2(1H)-one

1-phenyl-5-((p-tolylamino)methyl)pyridin-2(1H)-one

5-((4-methoxyphenylamino)methyl)-1-phenylpyridin-2(1H)-one

Refernces

• 1、 Chantarojsiri, Teera,Kittikool, Tanakorn,Phakdeeyothin, Kunita,Yotphan, Sirilata. "Manganese-Promoted Regioselective Direct C3-Phosphinoylation of 2-Pyridones". supporting information. p. 3071 - 3078. Retrieved 2021/07/22.
• 2、 -. "Preparation method of pirfenidone". Paragraph 0035; 0038; 0042-0043; 0047-0048; 0052-0053; 0057. . Retrieved 2020/07/28.