structure of Fasiglifam

Fasiglifam

CAS No.: 1000413-72-8
M. Wt: 524.625
M. Fa: C29H32O7S
InChI Key: BZCALJIHZVNMGJ-HSZRJFAPSA-N
Appearance: White Solid

Names and Identifiers of Fasiglifam

CAS Number

1000413-72-8

EC Number

805-621-8

MDL Number

MFCD18251445

IUPAC Name

2-[(3S)-6-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid

InChI

InChI=1S/C29H32O7S/c1-19-12-25(34-10-5-11-37(3,32)33)13-20(2)29(19)22-7-4-6-21(14-22)17-35-24-8-9-26-23(15-28(30)31)18-36-27(26)16-24/h4,6-9,12-14,16,23H,5,10-11,15,17-18H2,1-3H3,(H,30,31)/t23-/m1/s1

InChIKey

BZCALJIHZVNMGJ-HSZRJFAPSA-N

Canonical SMILES

CC1=CC(=CC(=C1C2=CC=CC(=C2)COC3=CC4=C(C=C3)C(CO4)CC(=O)O)C)OCCCS(=O)(=O)C

Isomeric SMILES

CC1=CC(=CC(=C1C2=CC=CC(=C2)COC3=CC4=C(C=C3)[C@@H](CO4)CC(=O)O)C)OCCCS(=O)(=O)C

UNII

GLP1W4JXAH

UNSPSC Code

12352100

Physical and chemical properties of Fasiglifam

Acidity coefficient

4.36±0.10(Predicted)

Boiling Point

739.1±60.0 °C at 760 mmHg

Density

1.3±0.1 g/cm3

Exact Mass

524.186890

Flash Point

400.8±32.9 °C

H Bond Acceptors

7

H Bond Donors

1

Index of Refraction

1.587

LogP

4.36

Melting Point

123-127°C

Molecular Formula

C29H32O7S

Molecular Weight

524.625

PSA

107.51000

Solubility

Acetonitrile (Slightly), DMSO (Slightly), Methanol (Slightly)

Storage condition

2-8℃

Vapour Pressure

0.0±2.6 mmHg at 25°C

Solubility of Fasiglifam

Solvent Dissolution Phenomenon Temperature Effect pH Effect
Water Insoluble or very slightly soluble Increasing temperature slightly enhances solubility, but overall solubility remains low Solubility slightly increases under acidic conditions (pH 1–3); solubility is lower under neutral and alkaline conditions
Ethanol Soluble Solubility increases with rising temperature pH has little effect, as it's a non-aqueous system
Methanol Freely soluble Rising temperature significantly improves solubility pH not applicable (non-aqueous solvent)
Dimethyl Sulfoxide (DMSO) Highly soluble (commonly used in vitro experiments) Completely miscible at high temperatures Hardly affected by pH
Acetone Soluble Solubility increases with rising temperature pH effect is negligible
Chloroform Soluble Increased temperature promotes dissolution Not affected by pH
Ethyl Acetate Slightly soluble to soluble Higher temperature aids dissolution pH has no direct effect

Safety Information of Fasiglifam

Pictograms

Signal Word

 Warning

Safety Data Sheet
Supports customized editing of SDS information and downloading in PDF documents.

Key Milestone of Fasiglifam

Time Milestone Event Detailed Description
2004 Compound Discovery and Initial Screening Takeda Pharmaceutical (Japan) discovered TAK-875, a novel G protein-coupled receptor GPR40 (also known as FFAR1) agonist with potential for promoting glucose-dependent insulin secretion, through high-throughput screening.
2008 First Human Clinical Trial (Phase I) Initiated Phase I clinical trials in healthy volunteers to evaluate the safety, pharmacokinetics, and preliminary efficacy of TAK-875. Results showed significant blood glucose-lowering effects with a low risk of hypoglycemia.
2010 Phase II Clinical Trials Launched Conducted multicenter, randomized, double-blind, placebo-controlled Phase II clinical studies in patients with type 2 diabetes. Results demonstrated that TAK-875 significantly improved HbA1c levels, outperforming placebo and some existing oral hypoglycemic drugs.
2011–2013 Ongoing Phase III Clinical Trials Launched multiple Phase III clinical trials globally (e.g., ZEAL, SAKE series) to evaluate long-term efficacy and safety, aiming to support a New Drug Application (NDA). Data indicated good glucose-lowering effects and cardiovascular safety.
2013 Emergence of Hepatotoxicity Signals Multiple subjects exhibited elevated liver enzymes (ALT/AST > 3×ULN) after long-term use, with some cases progressing to severe drug-induced liver injury, raising concerns about liver safety.
End of 2013 Takeda Announces Termination of Development Due to potential uncontrollable hepatotoxicity risks, Takeda Pharmaceutical announced the global discontinuation of all clinical development of TAK-875 and abandoned the New Drug Application.
2014 onwards Retained Scientific Value Although development was terminated, TAK-875, as the first GPR40 agonist to reach advanced clinical stages, remains an important reference and structural template for subsequent GPR40-targeted diabetes drug development.

Applications of Fasiglifam

Fasiglifam was primarily developed for managing type 2 diabetes mellitus but was also explored for potential applications in chronic kidney disease due to its effects on glucose metabolism and insulin sensitivity. Despite its promising profile, its clinical development was terminated following reports of liver toxicity during Phase III trials.

Interaction Studies of Fasiglifam

Interaction studies have revealed that fasiglifam may influence various hepatic transporters and metabolic pathways. It has shown inhibitory effects on multidrug resistance-associated proteins (MRPs), particularly MRP3, which could lead to altered bile acid transport and accumulation of toxic metabolites in liver cells. Additionally, the compound's interaction with mitochondrial respiration pathways has been studied, indicating potential mitochondrial toxicity at high concentrations.

Physical sample testing spectrum (NMR) of Fasiglifam

Physical sample testing spectrum (NMR) of Fasiglifam