946399-84-4

Basic information

• Product Name: 1-(4-Fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine
• Synonyms: 1-(4-Fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine;(R)-1-(4-fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine(WXG02471)
• CAS NO: 946399-84-4
• Molecular Formula: C₁₂H₁₄F₄N₂
• Molecular Weight: 262.2465728
• Mol File: 946399-84-4.mol
• Article Data: 5

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 1-(4-Fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(4-Fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine(946399-84-4)
• EPA Substance Registry System: 1-(4-Fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine(946399-84-4)

Safety Data

• Hazardous Substances Data: 946399-84-4(Hazardous Substances Data)

Usage

Chemical structure

Piperazine derivative with a fluorine atom and a trifluoromethyl group attached to the phenyl ring

Pharmaceutical use

Commonly used as a pharmaceutical ingredient

Therapeutic effects

Potential therapeutic effects in the treatment of various diseases and conditions

CNS stimulant

May act as a central nervous system stimulant

Neurological disorders

Studied for potential use in the treatment of neurological disorders such as depression and anxiety

Medicinal chemistry

May have applications in medicinal chemistry

Drug discovery research

May have applications in drug discovery research

Upstream product

• 40161-55-5 1-bromo-4-fluoro-2-(trifluoromethyl)benzene 
• 75336-86-6 (2R)-methylpiperazine 

Downstream Products

• 946399-89-9 (2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-1-(3-methoxyphenylsulfonyl)-2-methylpiperazine 
• 1186083-88-4 (2R)-1-(4-bromo-2-fluorophenylsulfonyl)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methylpiperazine 
• 946397-37-1 (2R)-N-[3-chloro-4-({4-[4-fluoro-2-(trifluoromethyl)phenyl]piperazin-1-yl}sulfonyl)phenyl]morpholine-4-carboxamide 
• 946398-85-2 (2R)-1-(4-bromo-2-chlorophenylsulfonyl)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methylpiperazine 
• 946398-83-0 (2R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-1-(4-methoxyphenylsulfonyl)-2-methylpiperazine 
• 946400-13-1 (2R)-1-(4-bromophenylsulfonyl)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methylpiperazine 
• 946398-94-3 (2R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methyl-1-(4-(trifluoromethoxy)-phenylsulfonyl)-piperazine 
• 946398-84-1 (2R)-4-(4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methylpiperazin-1-ylsulfonyl)benzonitrile 
• 946400-19-7 (2R)-3-chloro-4-(4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methylpiperazin-1-ylsulfonyl)benzonitrile 
• 946399-94-6 (R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methyl-1-(3-(3,3,3-trifluoroprop-1-en-2-yl)phenylsulfonyl)piperazine 
• 946399-93-5 (R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methyl-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfonyl)piperazine 
• 1257229-81-4 (2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methyl-1-(1H-1,2,4-triazol-5-ylsulfonyl)piperazine 
• 946398-15-8 (R)-1-(5-bromothiophen-2-ylsulfonyl)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methylpiperazine 
• 1257229-78-9 (2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methyl-1-(1,3-thiazol-2-ylsulfonyl)piperazine 

Relevant articles and documents

Synthesis of potent and orally efficacious 11β-hydroxysteroid dehydrogenase type 1 inhibitor HSD-016

Cortisol and the glucocorticoid receptor (GR) signaling pathway has been linked to the development of diabetes and metabolic syndrome. In vivo, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive cortisone to its active form, cortisol. Existing clinical data have supported 11β-HSD1 as a valid therapeutic target for type 2 diabetes. In our research program, (R)-1,1,1-trifluoro-2-(3-((R)-4-(4-fluoro-2- (trifluoromethyl)phenyl)-2-methylpiperazin-1-ylsulfonyl)phenyl)propan-2-ol (HSD-016) was discovered to be a potent, selective, and efficacious 11β-HSD1 inhibitor and advanced as a clinical candidate. Herein, a reliable and scalable synthesis of HSD-016 is described. Key transformations include an asymmetric synthesis of a chiral tertiary alcohol via Sharpless dihydroxylation, epoxide formation, and subsequent mild reduction. This route ensured multikilogram quantities of HSD-016 necessary for clinical studies.

Efficacious 11β-hydroxysteroid dehydrogenase type I inhibitors in the diet-induced obesity mouse model

Cortisol and the glucocorticoid receptor signaling pathway have been implicated in the development of diabetes and obesity. The reduction of cortisone to cortisol is catalyzed by 11β-hydroxysteroid dehydrogenase type I (11β-HSD1). 2,4-Disubsituted benzenesulfonamides were identified as potent inhibitors of both the human and mouse enzymes. The lead compounds displayed good pharmacokinetics and ex vivo inhibition of the target in mice. Cocrystal structures of compounds 1 and 20 bound to human 11α-HSD1 were obtained. Compound 20 was found to achieve high concentrations in target tissues, resulting in 95% inhibition in the ex vivo assay when dosed with a food mix (0.5 mg of drug per g of food) after 4 days. Compound 20 was efficacious in a mouse diet-induced obesity model and significantly reduced fed glucose and fasted insulin levels. Our findings suggest that 11β-HSD1 inhibition may be a valid target for the treatment of diabetes.

11-BETA HSD1 INHIBITORS

This invention relates to inhibiting 11βHSD1.