68489-09-8

Basic information

• Product Name: WS 12
• Synonyms: WS 12;(1R*,2S*)-N-(4-Methoxyphenyl)-5-methyl-2-(1-methylethyl)cyclohexanecarboxamide;CyclohexanecarboxaMide, N-(4-Methoxyphenyl)-5-Methyl-2-(1-Methylethyl)-, (1R,2S,5R)-;(2S,5R)-2-Isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexanecarboximide;(1R,2S,5R)-N-(4-METHOXYPHENYL)-5-METHYL-2-(1-METHYLETHYL)CYCLOHEXANECARBOXAMIDE;N- (4- methoxy phenyl) - menthol -3- carboxylase
• CAS NO: 68489-09-8
• Molecular Formula: C₁₈H₂₇NO₂
• Molecular Weight: 289.416
• Mol File: 68489-09-8.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 447.8±28.0 °C(Predicted)
• Appearance: white to off-white/
• Density: 1.029±0.06 g/cm3(Predicted)
• Vapor Pressure: 0-0Pa at 20-50℃
• Storage Temp.: Store at -20°C
• Solubility: DMSO: >20mg/mL
• PKA: 14.18±0.70(Predicted)
• CAS DataBase Reference: WS 12(CAS DataBase Reference)
• NIST Chemistry Reference: WS 12(68489-09-8)
• EPA Substance Registry System: WS 12(68489-09-8)

Safety Data

• Hazard Codes: N
• Statements: 50
• Safety Statements: 53-61
• RIDADR: UN 3077 9 / PGIII
• Hazardous Substances Data: 68489-09-8(Hazardous Substances Data)

Usage

Chemical Properties

WS 12 is a odorless white crystalline solid,mp 178 °C, displaying a strong initial cooling effect and a long-lastingness. It is used particularly is oral care flavors.

Uses

WS 12 is a potent TRPM8 agonist.

Trade name

Winsense WS-12 (Renessenz)

Biological Activity

Potent TRPM8 agonist that acts as a cooling agent (EC 50 = 193 nM).

Biochem/physiol Actions

WS-12 is a menthol derivative, that shows a specific binding affinity towards TRPM8 (transient receptor potential cation channel subfamily M member 8) receptor. TRPM8 is associated with prostate cancer and thus, WS-12 might be useful in reducing the progression of cancer.

Upstream product

• 16052-42-9 (1R,2S,5R)-menthyl chloride 
• 2216-51-5 (-)-menthol 
• 16052-40-7 (-)-(1R,3R,4S)-4-isopropyl-1-methylcyclohexane-3-carboxylic acid 
• 104-94-9 4-methoxy-aniline 

Relevant articles and documents

Synthesis, characterization and hplc analysis of the (1S,2S,5R)-diastereomer and the enantiomer of the clinical candidate ar-15512

AR-15512 (formerly known as AVX-012 and WS-12) is a TRPM8 receptor agonist currently in phase 2b clinical trials for the treatment of dry eye. This bioactive compound with menthol-like cooling activity has three stereogenic centers, and its final structure and absolute configuration, (1R,2S,5R), have been previously solved by cryo-electron microscopy. The route of synthesis of AR-15512 has also been reported, revealing that epimerization processes at the C-1 can occur at specific stages of the synthesis. In order to confirm that the desired configuration of AR-15512 does not change throughout the process and to discard the presence of the enantiomer in the final product due to possible contamination of the initial starting material, both the enantiomer of AR-15512 and the diastereomer at the C-1 were synthesized and fully characterized. In addition, the absolute configuration of the (1S,2S,5R)-diastereomer was determined by X-ray crystallographic analysis, and new HPLC methods were designed and developed for the identification of the two stereoisomers and their comparison with the clinical candidate AR-15512.

TRP-P8 ACTIVE COMPOUNDS AND THERAPEUTIC TREATMENT METHODS

Compounds of the disclosure provide compositions, which are effective for prophylaxis and treatment of diseases or disorders, such as cell-proliferation, angiogenesis, or apoptosis mediated diseases. The disclosure encompasses compounds, analogs, prodrugs, metabolites, and pharmaceutically acceptable salts thereof, pharmaceutical compositions, and methods for prophylaxis and treatment of diseases and other maladies or conditions involving cancer, tumors, and like conditions. The disclosure also provides therapeutic methods including the administration of an effective amount of a compound of the disclosure.