A77 1726

Base Information

• Chemical Name: A77 1726
• CAS No.: 163451-81-8
• Molecular Formula: C12H9F3N2O2
• Molecular Weight: 270.06
• Hs Code.: 2942000000
• Mol file: 163451-81-8.mol

Synonyms:(Z)-2-Cyano-a',a',a'-trifluoro-3-hydroxy-p-crotonotoluidide;

Chemical Property of A77 1726

Chemical Property:

• Vapor Pressure: 6.63E-06mmHg at 25°C
• Melting Point: 229-232°C
• Refractive Index: 1.551
• Boiling Point: 410.8 °C at 760 mmHg
• PKA: 5.20±0.50(Predicted)
• Flash Point: 202.3 °C
• PSA: 73.12000
• Density: 1.424 g/cm³
• LogP: 3.07248
• Storage Temp.: Hygroscopic, -20°C Freezer, Under Inert Atmosphere
• Solubility.: DMSO: soluble5mg/mL, clear (warmed)

Purity/Quality:

99% ^*data from raw suppliers

A77-1726 ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 22

MSDS Files:

SDS file from LookChem

Useful:

• Description: In September 2012, the US FDA approved teriflunomide (also referred to as HMR-1726) as a therapy for patients with relapsing forms of multiple sclerosis (MS). Teriflunomide is the second approved oral treatment option for MS, after Gilenya? which was approved in 2010. Teriflunomide, which is the active metabolite of leflunomide (a marketed drug for the treatment of rheumatoid and psoriatic arthritis), is a non?competitive and selective inhibitor of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme in the de novo synthesis of pyrimidines. Although the net effect of inhibition of DHODH by teriflunomide and its therapeutic effect in MS are not clear, it is hypothesized that by inhibiting de novo pyrimidine synthesis, the effector functions of activated lymphocytes are suppressed, thus dampening the effect of an overactive immune system. A-771726 is an active metabolite of the prodrug leflunomide that inhibits dihydroorotate dehydrogenase (DHODH; IC50 = 0.23 μM). A-771726 inhibits the production of prostaglandin E2 (PGE2; ) in TNF-α- or IL-1α-stimulated isolated human synoviocytes (IC50s = 7 and 3 μM, respectively). It inhibits the proliferation of isolated human peripheral blood mononuclear cells (PBMCs) when used at concentrations of 25 and 100 μM. A-771726 (3 and 10 mg/kg) delays disease onset and decreases neurological deficits in a rat model of experimental autoimmune encephalomyelitis (EAE) induced by complete Freund’s adjuvant (CFA) and M. tuberculosis. Formulations containing teriflunomide have been used in the treatment of multiple sclerosis.
• Uses: Teriflunomide has been used as a dihydroorotate dehydrogenase (DHODH) inhibitor. The active metabolite of Leflunomide, a potent disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis. LEF-M interferes with dendritic cell function. A-771726 is the active metabolite of leflunomide, a prodrug approved by the FDA for treatment of rheumatoid arthritis. A-771726 reversibly inhibits dihydroorotate dehydrogenase, the rate-limiting step in the de novo synthesis of pyrimidines. It prevents activated lymphocytes from accumulating sufficient pyrimidines to support DNA synthesis (IC50s = 0.09, 3.5, and 12.5 μM for rat, mouse, and human, respectively). At higher doses, A-771726 inhibits tyrosine kinases responsible for early T cell and B cell signaling in the G0/G1 phase of the cell cycle. A-771726 has also been shown to inhibit the production of prostaglandin E2 in synoviocytes activated by TNF-α and IL-1α (IC50s = 7 and 3 μM, respectively) as well as inhibit MMP-1 and IL-6 production at concentrations >10 μM.[Cayman Chemical]

Technology Process of A77 1726

There total 14 articles about A77 1726 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%

Leflunomide (75706-12-6) → teriflunomide (163451-81-8,108605-62-5)

Guidance literature:

Leflunomide; With sodium hydroxide; In water; isopropyl alcohol; at 30 ℃; pH=12;

With hydrogenchloride; at 30 ℃;

Reference yield: 92.0%

2-cyano-N-(4-trifluoromethylphenyl)acetamide (24522-30-3) + acetic anhydride (108-24-7) → teriflunomide (163451-81-8,108605-62-5)

Guidance literature:

2-cyano-N-(4-trifluoromethylphenyl)acetamide; With sodium hydroxide; In water; acetone; at 15 ℃;

acetic anhydride; In water; acetone; at 15 ℃; for 8.5h;

With hydrogenchloride; In water; at 5 - 10 ℃; for 2h; Product distribution / selectivity;

Reference yield: 88.3%

2-cyano-N-(4-trifluoromethylphenyl)acetamide (24522-30-3) + acetyl chloride (75-36-5) → teriflunomide (163451-81-8,108605-62-5)

Guidance literature:

2-cyano-N-(4-trifluoromethylphenyl)acetamide; With sodium hydride; In acetonitrile; for 0.166667h;

acetyl chloride; In acetonitrile; at 25 ℃; Cooling;

upstream raw materials:

Leflunomide

sodium cyanide

2-bromo-3-oxo-N-[4-(trifluoromethyl)phenyl]butanamide

5-methyl-1,2-oxazole-4-carboxylic acid

Downstream raw materials:

5-amino-3-methyl-isoxazole-4-carboxylic acid (4-trifluoromethyl-phenyl)-amide

Refernces

• 1、 -. "Preparation process of continuous-flow teriflunomide". Paragraph 0041; 0049-0053; 0061-0065; 0073-0076. . Retrieved 2021/11/21.
• 2、 Gerndt, Susanne,Chen, Cheng-Chang,Chao, Yu-Kai,Yuan, Yu,Burgstaller, Sandra,Rosato, Anna Scotto,Krogsaeter, Einar,Urban, Nicole,Jacob, Katharina,Nguyen, Ong Nam Phuong,Miller, Meghan T.,Keller, Marco,Vollmar, Angelika M.,Gudermann, Thomas,Zierler, Susanna,Schredelseker, Johann,Schaefer, Michael,Biel, Martin,Malli, Roland,Wahl-Schott, Christian,Bracher, Franz,Patel, Sandip,Grimm, Christian. "Agonist-mediated switching of ion selectivity in TPC2 differentially promotes lysosomal function". . . Retrieved 2020/05/08.