2765-91-5

Upstream product

• 67-56-1 methanol 
• 530-78-9 flufenamic acid 
• 610-97-9 o-iodo-methyl-benzoic acid 
• 98-16-8 3-trifluoromethylaniline 
• 17763-70-1 methyl 2-(trifluoromethylsulfonyloxy)benzoate 

Downstream Products

• 39492-79-0 2-(3-(trifluoromethyl)phenylamino)benzohydrazide 
• 530-78-9 flufenamic acid 
• 91855-65-1 4-n-Propyl-1-(3-trifluormethylphenyl)-3,4-dihydro-1H-1,4-benzodiazepin-2,5-dion 
• 91855-71-9 4-Propyl-1-(3-trifluoromethyl-phenyl)-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine 
• 91855-61-7 N-Chloracetyl-N-(3-trifluormethylphenyl)anthranilsaeuremethylester 

Relevant academic research and scientific papers

Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof

The invention includes compositions comprising selective AKR1C3 inhibitors. The invention also includes compositions comprising bifunctional AKR1C3 inhibitors and selective androgen receptor modulators. The invention further includes methods of treatment using the compositions of the invention.

Development of potent and selective inhibitors of aldo-keto reductase 1C3 (type 5 17β-hydroxysteroid dehydrogenase) based on N -phenyl-aminobenzoates and their structure-activity relationships

Aldo-keto reductase 1C3 (AKR1C3; type 5 17β-hydroxysteroid dehydrogenase) is overexpressed in castration resistant prostate cancer (CRPC) and is implicated in the intratumoral biosynthesis of testosterone and 5α-dihydrotestosterone. Selective AKR1C3 inhibitors are required because compounds should not inhibit the highly related AKR1C1 and AKR1C2 isoforms which are involved in the inactivation of 5α-dihydrotestosterone. NSAIDs, N-phenylanthranilates in particular, are potent but nonselective AKR1C3 inhibitors. Using flufenamic acid, 2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid, as lead compound, five classes of structural analogues were synthesized and evaluated for AKR1C3 inhibitory potency and selectivity. Structure-activity relationship (SAR) studies revealed that a meta-carboxylic acid group relative to the amine conferred pronounced AKR1C3 selectivity without loss of potency, while electron withdrawing groups on the phenylamino B-ring were optimal for AKR1C3 inhibition. Lead compounds did not inhibit COX-1 or COX-2 but blocked the AKR1C3 mediated production of testosterone in LNCaP-AKR1C3 cells. These compounds offer promising leads toward new therapeutics for CRPC.

Microwave-assisted one-step synthesis of fenamic acid hydrazides from the corresponding acids

A facile and efficient method for synthesis of fenamic acid hydrazides from their acids in one-step reaction under microwave irradiation and solvent-free conditions was developed. Compared with the two-step conventional heating method, the process was simple, the reaction time was very short and the yields were almost quantitative.

Discovery of substituted 3-(phenylamino)benzoic acids as potent and selective inhibitors of type 5 17β-hydroxysteroid dehydrogenase (AKR1C3)

Aldo-keto reductase 1C3 (AKR1C3) also known as type 5 17β- hydroxysteroid dehydrogenase has been implicated as one of the key enzymes driving the elevated intratumoral androgen levels observed in castrate resistant prostate cancer (CRPC). AKR1C3 inhibition therefore presents a rational approach to managing CRPC. Inhibitors should be selective for AKR1C3 over other AKR1C enzymes involved in androgen metabolism. We have synthesized 2-, 3-, and 4-(phenylamino)benzoic acids and identified 3-(phenylamino)benzoic acids that have nanomolar affinity and exhibit over 200-fold selectivity for AKR1C3 versus other AKR1C isoforms. The AKR1C3 inhibitory potency of the 4′-substituted 3-(phenylamino)benzoic acids shows a linear correlation with both electronic effects of substituents and the pKa of the carboxylic acid and secondary amine groups, which are interdependent. These compounds may be useful in treatment and/or prevention of CRPC as well as understanding the role of AKR1C3 in endocrinology.

Palladium-catalyzed one-step synthesis of isoindole-1,3-diones by carbonylative cyclization of o-halobenzoates and primary amines

(Chemical Equation Presented) The palladium-catalyzed aminocarbonylation of o-halobenzoates produces 2-substituted isoindole-1,3-diones in good yields. This methodology provides a good one-step approach to this important class of heterocycles and tolerates a variety of functional groups, including methoxy, alcohol, ketone, and nitro groups.

New esters of N arylanthranilic acids

A series of acyloxy and alkyloxymethyl esters of meclofenamic, flufenamic and mefenamic acids has been synthesized and its antiinflammatory, analgesic and antipyretic activities have been compared with those of the corresponding acids and the methyl, β,γ isopropylidenedioxypropyl, and N,N diethylaminoethyl esters. The acyloxy and alkyloxymethyl esters are the most interesting compounds, because they possess pharmacological activity of the same order as that of the corresponding acids and a lower toxicity. The ethoxymethyl ester of N (2,6 dichloro m tolyl)anthranilic acid is presently under clinical investigation.