1448428-04-3

Basic information

• Product Name: Selonsertib
• Synonyms: Selonsertib;5-(4-Cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methyl-N-[6-[4-(1-methylethyl)-4H-1,2,4-triazol-3-yl]-2-pyridinyl]benzamide;GS 4997;Selonsertib GS-4997;GS-4497;GS4997 SELONSERTIB;5-(4-Cyclopropyl-1H-imidazol-1-yl)-2-fluoro-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-methylbenzamide;Benzamide, 5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methyl-N-[6-[4-(1-methylethyl)-4H-1,2,4-triazol-3-yl]-2-pyridinyl]-
• CAS NO: 1448428-04-3
• Molecular Formula: C₂₄H₂₄FN₇O
• Molecular Weight: 445.4920632
• Product Categories: API
• Mol File: 1448428-04-3.mol

Chemical Properties

• Appearance: /
• Density: 1.39±0.1 g/cm3(Predicted)
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (>25 mg/ml)
• PKA: 11.21±0.70(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: Selonsertib(CAS DataBase Reference)
• NIST Chemistry Reference: Selonsertib(1448428-04-3)
• EPA Substance Registry System: Selonsertib(1448428-04-3)

Safety Data

• Hazardous Substances Data: 1448428-04-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Selonsertib is used as an anti-inflammatory agent for its potential to downregulate the expression of genes involved in fibrosis, cellular proliferation, and apoptosis by inhibiting the catalytic kinase domain of ASK1 and preventing its phosphorylation and activation.
Used in Anticancer Applications:
Selonsertib is used as an antineoplastic agent, contributing to the suppression of tumor growth and progression by modulating various oncological signaling pathways.
Used in Anti-fibrotic Treatments:
Selonsertib is used as an anti-fibrotic agent for the treatment of conditions characterized by excessive fibrosis, such as nonalcoholic steatohepatitis, by reducing hepatic steatosis, inflammation, and fibrosis.
Used in Drug Resistance Management:
Selonsertib is used to combat multidrug resistance in cancer treatment by suppressing the efflux function of MDR transporters ABCB1 and ABCG2, potentially enhancing the effectiveness of chemotherapeutic drugs.

in vitro

gs-4997 has been identified as a highly selective and potent ask1 inhibitor that competed with atp in the ask1 catalytic kinase domain. moreover, the ask1 inhibition caused by gs-4997 was found to be significantly different in mechanism from bardoxolone methyl. gs- 4997 could also shut down cell signaling involved in pathogenesis, while bardoxolone methyl activated mrna transcription in every cell exposed to drug. in addition, gs-4997 could selectively target affected cells in which the oxidative burden was high [1].

References

Lanier et al. (2017), Structure-Based Design of ASK1 Inhibitors as Potential Agents for Heart Failure; ACS Med. Chem. Lett. 8 316 Loomba et al. (2017), The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: a randomized, phase 2 trial; Hepatology 67 549 Younossi et al. (2018), Improvement of hepatic fibrosis and patient-reported outcomes in non-alcoholic steatohepatitis treated with selonsertib; Liver Int. 38 1849 Gawrieh and Chalasani (2018), Emerging Treatments for Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis; Clin. Liver Dis. 22 189 Ji et al. (2019), Selonsertib (GS-4997), an ASK1 inhibitor, antagonizes multidrug resistance in ABCB1- and ABCG2-overexpressing cancer cells; Cancer Lett. 440-441 82

Upstream product

• 75-31-0 isopropylamine 
• 69267-75-0 2-bromo-1-cyclopropylethan-1-one 
• 1448428-03-2 5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methylbenzoic acid hydrochloride 
• 1448427-99-3 6-[4-(propan-2-yl)-4H-1,2,4-triazol-3-yl]pyridin-2-amine 
• 36052-26-3 methyl 6-aminopyridine-2-carboxylate 
• 5584-18-9 6-aminopyridine-2-carbohydrazide 
• 19798-81-3 2-Amino-6-bromopyridine 
• 45644-21-1 6-chloropyridin-2-amine 
• 2402-78-0 2,6-dichloropyridine 
• 24463-56-7 4-isopropyl-1,2,4-triazole 
• 89830-98-8 4-cyclopropyl-1H-imidazole 
• 1448508-47-1 5-(4-cyclopropyl-1H-imidazole-1-yl)-2-fluoro-4-methylbenzoic acid 
• 81447-28-1 2-cyclopropyl-2-oxoethyl 4-methylbenzenesulfonate 
• 765-43-5 Cyclopropyl methyl ketone 

Relevant articles and documents

A ASK1 inhibitor synthesis process (by machine translation)

The invention discloses a ASK1 inhibitor synthesis process, relates to the technical field of drug synthesis. It is characterized by: the invention by improving the synthesis step and parameter, steps 1 and 2 synthesis of compound 3 of the cost is greatly reduced; the steps of the invention six reaction more completely, the yield is 56% raised to 86%; the steps of the invention seven jingjing ester exchange reaction in more moderate conditions, the reaction conversion is high; the steps of the invention eight do not need column chromatography, easy purification to obtain the high purity product, simple process, good stability. (by machine translation)

ASK1 INHIBITOR AND PREPARATION METHOD AND USE THEREOF

The present disclosure relates to a compound as shown in formula (II), a tautomer or a pharmaceutically acceptable salt thereof, and disclosed is the use thereof in preparing a drug for treating an ASK1-associated disease.

PROCESSES FOR PREPARING ASK1 INHIBITORS

The present disclosure provides processes for the preparation of a compound of formula (A) which exhibits apoptosis signal-regulating kinase ("ASK1") inhibitory activity and is thus useful in the treatment of diseases such as kidney disease, diabetic nephropathy and kidney fibrosis. The disclosure also provides compounds that are synthetic intermediates.

SOLID FORMS OF AN ASK1 INHIBITOR

Crystalline forms of 5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-4-methylbenzamide (Compound I) were prepared and characterized in the solid state: Also provided are processes of manufacture and methods of using the crystalline forms.