67589-15-5

Usage

Uses

Used in Pharmaceutical Industry:
2'-Hydroxy-5'-(trifluoromethyl)acetophenone is used as a key intermediate in the synthesis of benzoxazepine-based Orexin-2 receptor antagonists. These antagonists are being studied for their potential therapeutic applications in treating various disorders, such as insomnia, addiction, and other neurological conditions. The trifluoromethyl group in 2'-hydroxy-5'-(trifluoroMethyl)acetophenone enhances the drug's lipophilicity, leading to improved pharmacokinetic properties and increased receptor binding affinity.

Preparation

Preparation by reaction of acetyl chloride with p-(trifluoromethyl)phenol in hydrofluoric acid for 6 h to 100° under 3 atm (88%).

Upstream product

• 75-77-4 chloro-trimethyl-silane 
• 503464-99-1 1-(2-methoxy-5-(trifluoromethyl)phenyl)ethan-1-one 
• 402-52-8 methyl 4-(trifluoromethyl)phenyl ether 
• 1646630-04-7 N,N-diethyl-2-hydroxy-5-(trifluoromethyl)benzamide 
• 34857-71-1 4-trifluoromethylphenyl N,N-diethylcarbamate 
• 402-45-9 4-hydroxybenzotrifluoride 
• 97674-02-7 tributyl(1-ethoxyvinyl)stannane 
• 81107-97-3 2-bromo-4-(trifluoromethyl)phenol 
• 75-97-8 3,3-dimethyl-butan-2-one 

Downstream Products

• 1207618-02-7 2-bromo-1-[2-hydroxy-5-(trifluoromethyl)phenyl]ethanone 
• 1345731-86-3 tert-butyl {(R)-2-[2-acetyl-4-(trifluoromethyl)phenoxy]-1-methylethyl}carbamate 
• 1345731-58-9 (3R,5S)-4-(4-chlorobenzoyl)-3,5-dimethyl-7-(trifluoromethyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine 
• 1235407-24-5 (E)-3-(dimethylamino)-1-(2-hydroxy-5-(trifluoromethyl)phenyl)prop-2-en-1-one 
• 1235407-23-4 tert-butyl 3-[5-(5-trifluoromethyl-2-hydroxyphenyl)-1H-pyrazol-1-yl]azetidine-1-carboxylate 
• 1354819-31-0 tert-butyl 3-{5-[5-trifluoromethyl-2-(2-chloro-4-{[(2,4-dimethoxybenzyl)(1,3,4-thiadiazol-5-yl)amino]sulfonyl}-5-fluorophenoxy)phenyl]-1H-pyrazol-1-yl}azetidine-1-carboxylate 
• 1354818-96-4 4-[2-(1-azetidin-3-yl-1H-pyrazol-5-yl)-5-chloro-2-fluoro-4-(trifluoromethyl)phenoxy]-N-1,3,4-thiadiazol-5-yl benzenesulfonamide 
• 1354818-97-5 5-chloro-2-fluoro-4-{4-trifluoromethyl-2-[1-(1-methylazetidin-3-yl)-1H-pyrazol-5-yl]phenoxy}-N-1,3,4-thiadiazol-ylbenzenesulfonamide 
• 1441772-97-9 3-hydroxy-6-(trifluoromethyl)-2-(2,4,5-trimethoxyphenyl)-4H-chromen-4-one 

Relevant academic research and scientific papers

ALLOSTERIC CHROMENONE INHIBITORS OF PHOSPHOINOSITIDE 3-KINASE (PI3K) FOR THE TREATMENT OF DISEASES ASSOCIATED WITH P13K MODULATION

The disclosure relates to compounds of Formula (I) as allosteric chromenone inhibitors of phosphoinositide 3-kinase (PI3K) useful in the treatment of diseases or disorders associated with PI3K modulation, Formula (I), or a prodrug, solvate, enantiomer, st

Discovery of Clinical Candidate 4-[2-(5-Amino-1H-pyrazol-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-1,3-thiazol-4-ylbenzenesulfonamide (PF-05089771): Design and Optimization of Diaryl Ether Aryl Sulfonamides as Selective Inhibitors of NaV1.7

A series of acidic diaryl ether heterocyclic sulfonamides that are potent and subtype selective NaV1.7 inhibitors is described. Optimization of early lead matter focused on removal of structural alerts, improving metabolic stability and reducing cytochrome P450 inhibition driven drug-drug interaction concerns to deliver the desired balance of preclinical in vitro properties. Concerns over nonmetabolic routes of clearance, variable clearance in preclinical species, and subsequent low confidence human pharmacokinetic predictions led to the decision to conduct a human microdose study to determine clinical pharmacokinetics. The design strategies and results from preclinical PK and clinical human microdose PK data are described leading to the discovery of the first subtype selective NaV1.7 inhibitor clinical candidate PF-05089771 (34) which binds to a site in the voltage sensing domain.

Discovery, Structure-Activity Relationship, and Antiparkinsonian Effect of a Potent and Brain-Penetrant Chemical Series of Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4

The metabotropic glutamate receptor 4 (mGluR4) is an emerging target for the treatment of Parkinson's disease (PD). However, since the discovery of its therapeutic potential, no ligand has been successfully developed enough to be tested in the clinic. In the present paper, we report for the first time the medicinal chemistry efforts conducted around the pharmacological tool (-)-PHCCC. This work led to the identification of compound 40, a potent and selective mGluR4 positive allosteric modulator (PAM) with good water solubility and demonstrating consistent activity across validated preclinical rodent models of PD motor symptoms after intraperitoneal administration: haloperidol-induced catalepsy in mouse and the rat 6-hydroxydopamine (6-OHDA) lesion model. Moreover, we also describe the identification of compound 60 a close analogue of compound 40 with improved pharmacokinetic profile after oral administration. On the basis of its favorable and unique preclinical profile, compound 60 (PXT002331, now foliglurax) was nominated as a candidate for clinical development.

Lithiation of a silyl ether: Formation of an ortho-fries hydroxyketone

A hydroxy-directed alkylation of an N,N-diethylarylamide using CIPE-assisted α-silyl carbanions (CIPE=complex-induced proximity effect) has been developed using a simple reagent combination of LDA (lithium diisopropylamide) and chlorosilane. A study of the mechanism, and the application of the procedure to an anionic Snieckus-Fries rearrangement for a highly efficient synthesis of the potent phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, are reported.

CHEMICAL COMPOUNDS

The invention relates to new sulfonamide Nav1.7 inhibitors and pharmaceutically acceptable salts thereof, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. Nav 1.7 in

Discovery of potent selective orally active benzoxazepine-based orexin-2 receptor antagonists

During our efforts to identify a series of potent, selective, orally active human Orexin-2 Receptor (OX2R) antagonists, we elucidated structure-activity relationship (SAR) on the 7-position of a benzoxazepine scaffold by utilizing Hammett rp and Hansch-Fu

NOVEL OXIME DERIVATIVES AND THEIR USE AS ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS

The present invention provides new oxime derivatives of the general formula (I), pharmaceutical compositions containing them and their use for the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions

THIAZOLE COMPOUNDS AS ACTIVATORS OF SOLUBLE GUANYLATE CYCLASE

Disclosed are compounds of formula (I) wherein R1 and R2 are independently selected from hydrogen, halo, C1-4alkyl, C1-4alkoxy, CF3 and OCF3; -Y- represents formula (IA) R3 represents hydrogen, fluoro, chloro or C1-4alkyl; R4a and R4b each independently represent hydrogen, C1-4alkyl, C1-4alkoxy, CF3 or halo; and R5 represents a group Z-X; wherein Z is absent or represents (CH2)2 or O; and X represents formula (IB) wherein: J and L both represent CH, or one of J and L represents CH and the other represents N; when both J and L represent CH, R6 represents hydrogen, halo, CF3, C1-4alkyl or C1-4alkoxy in a meta or ortho position relative to the R7 substituent and R7 represents hydrogen, halo, CF3, OCF3, C1-4alkyl, C1-4alkoxy, CH2OH, CN, CONR8R9 or CO2H; or when one of J or L represents N, R6 represents hydrogen or halo in a meta or ortho position relative to the R7 substituent and R7 represents hydrogen, halo, CF3, C1-4alkyl, C1-4alkoxy, CH2OH, CN, CONR8R9 or CO2H; and R8 and R9 are independently selected from hydrogen and C1-4alkyl; or salts thereof which activate soluble guanylate cyclase (sGC), pharmaceutical compositions containing them, their use in medicine, and processes for their preparation.

SPIROKETONE ACETYL-COA CARBOXYLASE INHIBITORS

The invention provides compounds of Formula (1) or a pharmaceutically acceptable salt of said compound, wherein R1, R2, R3, R4, R5, R6, R7, R8 and R9 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating mammals suffering from the condition of being overweight.

Process for producing 4-substituted benzopyran derivatives

The present invention relates to a first process for producing a 2,2-bis(fluoromethyl)-6-(perfluoroalkyl)-2H-1-benzopyran-4-carboxylic acid. The first process includes the steps of (a) reacting a 2,2-bis(fluoromethyl)-6-(perfluoroalkyl)-2H-1-benzopyran-4-