Saroglitazar

Base Information

• Chemical Name: Saroglitazar
• CAS No.: 495399-09-2
• Molecular Formula: C25H29NO4S
• Molecular Weight: 439.57
• Mol file: 495399-09-2.mol

Synonyms:Saroglitazar

Chemical Property of Saroglitazar

Chemical Property:

• Boiling Point: 621.0±55.0 °C(Predicted)
• PKA: 3.60±0.10(Predicted)
• PSA: 85.99000
• Density: 1.15±0.1 g/cm3(Predicted)
• LogP: 5.29660
• Storage Temp.: Refrigerator
• Solubility.: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)

Purity/Quality:

98% min ^*data from raw suppliers

Saroglitazar ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Saroglitazar (also known as ZYH1) was approved for use by the Drug Controller General of India for the treatment of diabetic dyslipidemia and hypertriglyceridemia that is not controlled by statin therapy. Saroglitazar is the first approved agent with dual PPAR agonist activity, with EC50s of 0.00065 and 3 nM, respectively, for the α- and γ-PPAR isoforms in HepG2 cells. The medicinal chemistry program has not been described in the scientific literature, but numerous substituents on the pyrrole ring are described in the saroglitazar patent. These substituted pyrroles were synthesized via ethanolamine condensation with substituted diketones and subsequent activation of the hydroxyethylpyrrole for phenolic etherification with (S)-2- ethoxy-3-(4-hydroxyphenyl)propanoic acid. The efficacy of saroglitazar was evaluated in db/db mice (genetically diabetic animals that lack the leptin receptor), wherein it produced a 17–55% reduction in serum triglycerides (TGs) after 12 days of administration of saroglitazar (0.01–3 mg/kg). Saroglitazar is a dual agonist of PPARα and PPARγ (EC50s = 0.65 and 3,000 pM, respectively, in a transactivation assay in HepG2 cells). It decreases serum triglyceride, free fatty acid, and glucose levels in a db/db mouse model of diabetes when administered at doses ranging from 0.01 to 3 mg/kg per day for 12 days. It increases insulin sensitivity in an oral glucose challenge when administered at a dose of 1 mg/kg in db/db mice, as well as decreases LDL levels in hApoB100/hCETP mice and in hamsters fed a high-fat high-cholesterol diet. Saroglitazar (10 μM) reverses palmitic acid-induced decreases in the expression of superoxide dismutase 1 (SOD1), SOD2, glutathione peroxidase (GPX), and catalase and increases in TNF-α, IL-1β, and IL-6 expression in HepG2 cells. It decreases hepatic inflammation and steatosis in a mouse model of non-alcoholic steatohepatitis (NASH) induced by a choline-deficient high-fat diet when administered at a dose of 3 mg/kg and inhibits fibrosis in a mouse model of fibrosis induced by carbon tetrachloride.
• Uses: Saroglitazar, is a drug for the treatment of diabetic dyslipidemia and hypertriglyceridemia with Type 2 diabetes mellitus not controlled by statin therapy. Its trade name is Lipaglyn. It is also a 1,2-Diarylpyrroles derivative, which can be used in the preparation of Nonsteroidal anti-inflammatory drugs (NSAIDs).

Technology Process of Saroglitazar

There total 7 articles about Saroglitazar 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: 99.0%

→ (S)-2-ethoxy-3-(4-(2-(2-methyl-5-(4-(methylthio)phenyl)-1H-pyrrol-1-yl)ethoxy)phenyl)propanoic acid (495399-09-2)

Guidance literature:

Reference yield:

ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)propanoate (222555-06-8) → (S)-2-ethoxy-3-(4-(2-(2-methyl-5-(4-(methylthio)phenyl)-1H-pyrrol-1-yl)ethoxy)phenyl)propanoic acid (495399-09-2)

Guidance literature:

Multi-step reaction with 2 steps

1.1: potassium carbonate / cyclohexane / 0.5 h / 45 - 55 °C / Inert atmosphere

1.2: 36 h / 75 - 85 °C

2.1: sodium hydroxide; water / ethanol / 3 h / 25 °C / Inert atmosphere

With water; potassium carbonate; sodium hydroxide; In ethanol; cyclohexane;

Reference yield:

(S)-(-)α-1-phenylethylamine salt of (S)-α-ethoxy-4-[2-[-methyl-5-[4-(methylthio) phenyl]-1H-pyrrol-1-yl]ethoxy]benzene-propanoic acid (1392592-61-8) → (S)-2-ethoxy-3-(4-(2-(2-methyl-5-(4-(methylthio)phenyl)-1H-pyrrol-1-yl)ethoxy)phenyl)propanoic acid (495399-09-2)

Guidance literature:

With hydrogenchloride; water; In ethyl acetate; at 20 ℃; for 0.166667h; Solvent; Temperature; Inert atmosphere;

upstream raw materials:

(S)-(-)α-1-phenylethylamine salt of (S)-α-ethoxy-4-[2-[-methyl-5-[4-(methylthio) phenyl]-1H-pyrrol-1-yl]ethoxy]benzene-propanoic acid

ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)propanoate

methanesulfonic acid 2-[2-methyl-5-(4-methylsulfanyl-phenyl)-pyrrol-1-yl]-ethyl ester

Downstream raw materials:

(S)-2-ethoxy-3-(4-(2-(2-methyl-5-(4-(methylthio)phenyl)-1H-pyrrol-1-yl)ethoxy)phenyl)propanoic acid sodium salt

(S)-α-ethoxy-4-[2-[-methyl-5-[4-(methylthio)phenyl]-1H-pyrrol-1-yl]ethoxy]benzenepropanoic acid potassium salt

Refernces

• 1、 -. "SYNERGISTIC COMPOSITIONS". Page/Page column 45. . Retrieved 2015/01/16.
• 2、 -. "AN IMPROVED PROCESS FOR THE PREPARATION OF PYRROLE DERIVATIVES". Page/Page column 42; 43. . Retrieved 2015/03/28.