| Identification | Back Directory | [Name]
Saroglitazar | [CAS]
495399-09-2 | [Synonyms]
Saroglitazar
Benzenepropanoic acid, α-ethoxy-4-[2-[2-methyl-5-[4-(methylthio)phenyl]-1H-pyrrol-1-yl]ethoxy]-, (αS)- | [Molecular Formula]
C25H29NO4S | [MDL Number]
MFCD28502034 | [MOL File]
495399-09-2.mol | [Molecular Weight]
439.57 |
| Chemical Properties | Back Directory | [Boiling point ]
621.0±55.0 °C(Predicted) | [density ]
1.15±0.1 g/cm3(Predicted) | [storage temp. ]
Refrigerator | [solubility ]
Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly) | [form ]
Gel | [pka]
3.60±0.10(Predicted) | [color ]
Red |
| Hazard Information | Back Directory | [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). | [Originator]
Cadila Healthcare Ltd. (India) | [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). | [Definition]
ChEBI: Saroglitazar is a monocarboxylic acid that is (2S)-2-ethoxy-3-(p-ethoxyphenyl)propanoic acid in which one of the methyl hydrogens of the p-ethoxy substituent has been replaced by the nitrogen of 2-methyl-5-[4-(methylthio)phenyl]-1H-pyrrole. An agonist at the subtypes alpha and gamma of the peroxisome proliferator-activated receptor (PPAR) with predominant PPARalpha activity, it is used in the treatment of type 2 diabetes. It has a role as a PPARgamma agonist, a hypoglycemic agent and a PPARalpha agonist. It is a member of pyrroles, a monocarboxylic acid, a methyl sulfide and an aromatic ether. | [Brand name]
Lipaglyn | [Synthesis]
The sequence began with a Paal¨CKnorr pyrrole synthesis starting
from commercial 1-[4-(methylthio)phenyl]pentane-1,4-dione
(148). Subjection of this diketone to ethanolamine in warm pivalic
acid furnished pyrrole 149, which was taken forward as the crude
product. Next, the alcohol was mesylated to afford 150, which was used without further purification. Williamson ether conditions
were employed to convert mesylate 150 to the corresponding aryl
ether 152 through the use of commercial phenol 151 and anhydrous
potassium carbonate. This reaction proceeded in 80% yield.
Saponification of the terminal ethyl ester using sodium hydroxide
followed by acidic pH adjustment ultimately delivered the carboxylic
acid drug saroglitazar (XX) in 98% yield from 152.
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