Tafamidis

Base Information

• Chemical Name: Tafamidis
• CAS No.: 594839-88-0
• Molecular Formula: C14H7Cl2NO3
• Molecular Weight: 308.12
• European Community (EC) Number: 813-715-5
• UNII: 8FG9H9D31J
• DSSTox Substance ID: DTXSID00208185
• Nikkaji Number: J1.930.213J
• Wikipedia: Tafamidis
• Wikidata: Q519447
• NCI Thesaurus Code: C84193
• RXCUI: 1545063
• Pharos Ligand ID: 45CWA8GX7BAP
• Metabolomics Workbench ID: 152765
• ChEMBL ID: CHEMBL2103837
• Mol file: 594839-88-0.mol

Synonyms:FX 1006A;FX-1006A;FX1006A;tafamidis;tafamidis meglumine;Vyndamax;Vyndaqel

Chemical Property of Tafamidis

Chemical Property:

• Boiling Point: 486.7±40.0 °C(Predicted)
• PKA: 3.49±0.30(Predicted)
• PSA: 63.33000
• Density: 1.530
• LogP: 4.49980
• Storage Temp.: -20°
• Solubility.: Soluble in DMSO (up to 20 mg/ml).
• XLogP3: 4.2
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 2
• Exact Mass: 306.9802985
• Heavy Atom Count: 20
• Complexity: 371

Purity/Quality:

97% ^*data from raw suppliers

PF-06291826(Tafamidis) >98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1=CC2=C(C=C1C(=O)O)OC(=N2)C3=CC(=CC(=C3)Cl)Cl
• Recent ClinicalTrials: This Study Will Examine the Clinical Effectiveness of Tafamidis in Patients With Mixed Phenotype Hereditary Transthyretin Amyloidosis
• Recent EU Clinical Trials: A PHASE 3 MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE SAFETY OF DAILY ORAL DOSING OF
• Recent NIPH Clinical Trials: Pathophysiological impacts of tafamidis on cardiac transthyretin amyloidosis
• Description: Tafamidis is a kinetic stabilizer of transthyretin (TTR) that prevents amyloidogenesis by wild-type and mutant TTRs. It binds to TTR with negative cooperativity (Kd1 = 3 nM; Kd2 = 278 nM) to stabilize the TTR dimer-dimer interface and inhibit tetrameric dissociation. Tafamidis stabilizes wild-type and clinically significant V30M and V122I mutant TTR amyloidogenic homotetramers (EC50s = 2.7-3.2 μM) under fibril-promoting, denaturing, and physiological conditions in vitro. It stabilizes TTR heterotetramers containing wild-type and mutant subunits ex vivo in human plasma derived from patients carrying V30M or V1221 mutations when used at a concentration of 7.2 μM. Formulations containing tafamidis have been used for the treatment of familial amyloid polyneuropathy.
• Uses: Tafamidis can be used as a benzoxole derivative that is a transthyretin (TTR) amyloid fibril inhibitors. It is a new drug candidate in the treatment of TTR amyloidosis (caused my misfolding of proteins).

Technology Process of Tafamidis

There total 35 articles about Tafamidis 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: 94.0%

1,3-dichloro-5-(trimethoxymethyl)benzene + 4-aminosalicylic acid (2374-03-0) → 2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid (594839-88-0)

Guidance literature:

With trifluoroacetic acid; In methanol; at 60 ℃; Reagent/catalyst; Solvent; Temperature; Catalytic behavior;

Reference yield: 94.0%

4-(3,5-dichlorophenyl-6-benzoxazoyl)morpholine → 2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid (594839-88-0)

Guidance literature:

4-(3,5-dichlorophenyl-6-benzoxazoyl)morpholine; With pyridine hydrogenfluoride; In tetrahydrofuran; at 70 ℃; for 12h; Inert atmosphere;

With sodium hydrogencarbonate; In tetrahydrofuran; ethyl acetate; Inert atmosphere;

With hydrogenchloride; In tetrahydrofuran; water; ethyl acetate; Inert atmosphere;

DOI:10.1002/chem.201101091

Reference yield: 92.0%

3,5-dichlorobenzyl alcohol (60211-57-6) + 4-aminosalicylic acid (2374-03-0) → 2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid (594839-88-0)

Guidance literature:

3,5-dichlorobenzyl alcohol; With oxygen; at 106 ℃; for 0.216667h; under 3800.26 Torr; Flow reactor; Green chemistry;

4-aminosalicylic acid; at 106 ℃; Flow reactor; Green chemistry;

at 106 ℃; for 0.666667h; Flow reactor; Green chemistry;

DOI:10.1039/c9gc01641d

upstream raw materials:

1,3-benzoxazole-6-carboxylic Acid

4-(6-benzoxazoyl)morpholine

4-aminosalicylic acid

3,5-dichlorobenzoyl chloride