216665-24-6

Upstream product

• 393-11-3 4-nitro-3-(trifluoromethyl)benzeneamine 
• 106089-20-7 (S)-(-)-3-bromo-2-hydroxy-2-methylpropanoic acid 
• 1010396-30-1 (R)-3-bromo-2-hydroxy-2-methylpropanoyl chloride 

Downstream Products

• 476314-51-9 3-(4-amino-phenylsulfanyl)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide 
• 401900-41-2 3-(4-fluoro-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide 
• 348597-81-9 (S)-N-(4-nitro-3-(trifluoromethyl)phenyl)-2-methyloxirane-2-carboxamide 
• 737795-96-9 (R)-{4-[2-hydroxy-2-(4-nitro-3-trifluoromethylphenylcarbamoyl)propoxy]phenyl}carbamic acid tert-butyl ester 
• 476314-54-2 3-(4-acetylamino-phenylsulfanyl)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide 
• 476314-55-3 3-[4-(2-chloro-acetylamino)-phenylsulfanyl]-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide 
• 885324-25-4 (2R)-3-(4-acetamidophenoxy)-N-[(4-nitro-3-(trifluoromethyl)phenyl)]-2-hydroxy-2-methylpropanamide 

Relevant academic research and scientific papers

Synthetic method of alpha-hydroxypropanamide derivatives with optical activity

The invention discloses a synthetic method of alpha-hydroxypropanamide derivatives with optical activity and belongs to the field of organic synthesis. Proline taken as a chiral auxiliary, as well asmethacryloyl chloride, is subjected to acylation, bromination and chiral auxiliary removal, a product and 4-cyano-3-trifluoromethylaniline are subjected to nucleophilic substitution, and 3-bromo-2-hydroxy-2-methyl-N-[(4-cyano-3-trifluoromethyl)phenyl]propanamide is obtained and subjected to nucleophilic substitution with 4-cyanophenol, and the compound 3-(4-cyanophenoxy)-N-[4-cyano-3-(trifluoromethylphenyl]-2-hydroxy-2-methylpropanamide with optical activity is prepared. 3-bromo-2-hydroxy-2-methyl propionic acid and 4-nitro-3-trifluoromethylaniline are subjected to aminolysis, a product is subjected to nucleophilic substitution with paracetamol, and the compound 3-(4-acetoxyphenoxy)-N-[4-nitro-3-(trifluoromethylphenyl]-2-hydroxy-2-methylpropanamide with optical activity is prepared. The efficient synthetic method of the alpha-hydroxypropanamide derivatives with optical activity is provided.

Prostate cancer PET bioprobes: Synthesis of [18F]-radiolabeled hydroxyflutamide derivatives

Approximately 80-90% of prostate cancers are androgen dependent at initial diagnosis. The androgen receptor (AR) is present in most advanced prostate cancer specimens and is believed to have a critical role in its development. Today, treatment of prostate cancer is done by inhibition of AR using antiandrogens such as flutamide (pro-drug of hydroxyflutamide), nilutamide, and bicalutamide. However, there is currently no noninvasive imaging modalities to detect, guide, and monitor specific treatment of AR-positive prostate cancer. (R)-3-Bromo-N-(4-fluoro-3-(trifluoromethyl)phenyl)-2-hydroxy-2-methyl- propanamide [18F]-1 and N-(4-fluoro-3-(trifluoromethyl)phenyl)-2- hydroxy-2-methylpropanamide [18F]-2, derivatives of hydroxyflutamide, were synthesized as a fluorine-containing imaging agent candidates. A three-step fluorine-18 radiosynthesis route was developed, and the compounds were successfully labeled with a 10 ± 3% decay corrected radiochemical yield, 95% radiochemical purity, and a specific activity of 1500 ± 200 Ci/mmol end of bombardment (n = 10). These labeled biprobes not only may enable for the future quantitative molecular imaging of AR-positive prostate cancer using positron emission tomography but may also allow for image-guided treatment of prostate cancer.

Homology modeling using multiple molecular dynamics simulations and docking studies of the human androgen receptor ligand binding domain bound to testosterone and nonsteroidal ligands

To facilitate the rational design of novel and more potent androgen receptor ligands, three-dimensional models for the human androgen receptor ligand binding domain bound to testosterone have been developed. These models of the androgen receptor were based on the crystal structure of the highly homologous human progesterone receptor ligand binding domain. The homology modeled androgen receptor was refined using unrestrained multiple molecular dynamics simulations in explicit solvent. Key H-bonding partners with the 17-hydroxy group and 3-keto group of testosterone are Asn705 and Thr877, and Gln711 and Arg752, respectively. These models show the presence of a unique unoccupied cavity within the androgen receptor binding pocket which may be valuable in the development of novel selective androgen receptor ligands. A qualitative analysis of amino acid mutations within the hAR binding pocket that affect ligand binding are consistent with these androgen receptor models. In addition to testosterone, the binding modes of several hydroxyflutamide-like nonsteroidal ligands for the androgen receptor are investigated using flexible docking with FlexX followed by refinement of the initial complexes with molecular dynamics simulations. These docking studies indicate that Asn705 is an important determinant in binding hydroxyflutamide and its derivatives by participating in H-bond interactions with the α-hydroxy moiety of these ligands. In addition, the nitro functionality mimics the 3-keto group of the natural ligand testosterone and is involved in H-bonding interactions with Gln711 and Arg752. From these docking studies, we suggest a mechanism for the enantioselective binding of chiral hydroxyflutamide derivatives and expand upon the previously reported structure-activity relationship for hydroxyflutamide and its derivatives.