52209-61-7

Upstream product

• 463-71-8 thiophosgene 
• 393-11-3 4-nitro-3-(trifluoromethyl)benzeneamine 

Downstream Products

• 1214896-22-6 1-benzyl-3-(4-nitro-3-(trifluoromethyl)phenyl)-2-thioxotetrahydropyrimidin-4(1H)-one 
• 1214896-36-2 1-ethyl-3-(4-nitro-3-(trifluoromethyl)phenyl)-2-thioxotetrahydropyrimidin-4(1H)-one 
• 1214896-10-2 3-(4-nitro-3-(trifluoromethyl)phenyl)-1-(1-phenylethyl)-2-thioxotetrahydropyrimidin-4(1H)-one 
• 1417456-65-5 C₁₂H₁₂F₃N₃O₄S 
• 1417456-59-7 C₁₁H₁₀F₃N₃O₄S 
• 1417455-95-8 3-(4-nitro-3-(trifluoromethyl)phenyl)-2-thioxotetrahydropyrimidin-4(1H)-one 
• 1417456-17-7 3-(4-nitro-3-(trifluoromethyl)phenyl)-6-methyl-2-thioxotetrahydropyrimidin-4(1H)-one 
• 1315245-42-1 5-methyl-3-(4-nitro-3-(trifluoromethyl)phenyl)-4-oxo-2-thioxoimidazolidine 

Relevant academic research and scientific papers

A new series of bicalutamide, enzalutamide and enobosarm derivatives carrying pentafluorosulfanyl (SF5) and pentafluoroethyl (C2F5) substituents: Improved antiproliferative agents against prostate cancer

SAR studies on bicalutamide, enobosarm and enzalutamide analogues, functionalised with polyfluorinated groups, is presented. Among the novel bicalutamide and enobosarm derivatives synthesised, several displayed significantly improved in vitro anticancer activity, with IC50 values in the low micromolar range against four different prostate cancer cell lines (LNCaP, VCaP, DU-145 and 22Rv1), showing up to 48-fold increase in comparison with the parent structures. In particular, SF5 enobosarm analogues were found to be most potent compounds, full AR antagonists and with favourable ADME properties. The most promising compound (48a) was evaluated for its in vivo efficacy in PC xenograft mouse model (22Rv1) with results comparable to the standard-of-care docetaxel.

Highly Acidic Conjugate-Base-Stabilized Carboxylic Acids Catalyze Enantioselective oxa-Pictet–Spengler Reactions with Ketals

Acyclic ketone-derived oxocarbenium ions are involved as intermediates in numerous reactions that provide valuable products, however, they have thus far eluded efforts aimed at asymmetric catalysis. We report that a readily accessible chiral carboxylic acid catalyst exerts control over asymmetric cyclizations of acyclic ketone-derived trisubstituted oxocarbenium ions, thereby providing access to highly enantioenriched dihydropyran products containing a tetrasubstituted stereogenic center. The high acidity of the carboxylic acid catalyst, which exceeds that of the well-known chiral phosphoric acid catalyst TRIP, is largely derived from stabilization of the carboxylate conjugate base through intramolecular anion-binding to a thiourea site.

Design and synthesis of novel bicalutamide and enzalutamide derivatives as antiproliferative agents for the treatment of prostate cancer

Prostate cancer (PC) is one of the major causes of male death worldwide and the development of new and more potent anti-PC compounds is a constant requirement. Among the current treatments, (R)-bicalutamide and enzalutamide are non-steroidal androgen receptor antagonist drugs approved also in the case of castration-resistant forms. Both these drugs present a moderate antiproliferative activity and their use is limited due to the development of resistant mutants of their biological target. Insertion of fluorinated and perfluorinated groups in biologically active compounds is a current trend in medicinal chemistry, applied to improve their efficacy and stability profiles. As a means to obtain such effects, different modifications with perfluoro groups were rationally designed on the bicalutamide and enzalutamide structures, leading to the synthesis of a series of new antiproliferative compounds. Several new analogues displayed improved in vitro activity towards four different prostate cancer cell lines, while maintaining full AR antagonism and therefore representing promising leads for further development. Furthermore, a series of molecular modelling studies were performed on the AR antagonist conformation, providing useful insights on potential protein-ligand interactions.

ANDROGEN RECEPTOR MODULATORS AND THEIR USE AS ANTI-CANCER AGENTS

Compounds having therapeutic potential as androgen receptor modulators and anti- cancer agents, and methods of making such compounds, are provided. The compounds are structurally related to bicalutamide, enobosarm and enzalutamide, but bear at least one S

ANDROGEN RECEPTOR MODULATORS AND THEIR USE AS ANTI-CANCER AGENTS

Compounds having therapeutic potential as androgen receptor modulators and anti- cancer agents, and methods of making such compounds, are provided. The compounds are structurally related to bicalutamide, enobosarm and enzalutamide, but bear a 3,5-bis- CF

Rational design and synthesis of novel anti-prostate cancer agents bearing a 3,5-bis-trifluoromethylphenyl moiety

Prostate cancer is a major cause of male death worldwide and the identification of new and improved treatments is constantly required. Among the available options, different non-steroidal androgen receptor (AR) antagonists are approved also to treat castration-resistant forms. Most of these drugs show limited application due to the development of resistant mutants of their biological target. Following docking-based studies on a homology model for the AR open antagonist conformation, a series of novel 3,5-bis-trifluoromethylphenyl compounds was designed with the aim to improve the antiproliferative activity of anti-androgen drugs bicalutamide and enzalutamide. The new structural modifications might impede the receptor to adopt its closed agonist conformation also in the presence of adaptive mutations. Among the novel compounds synthesised, several displayed significantly improved in vitro activity in comparison with the parent structures, with IC50values in the low micromolar range against four different prostate cancer cell lines (LNCaP, VCaP, DU-145, 22Rv1). Selected hits demonstrated full AR antagonistic behaviour and promising candidates for further development were identified.

Aldol derivatives of Thioxoimidazolidinones as potential anti-prostate cancer agents

The paper discusses the synthesis and stereochemical aspects of the anti aldol products, 3-(substituted phenyl)-5-[(substituted phenyl) hydroxy methyl]-5-methyl-4-oxo-2-thioxoimidazolidines. The stereochemistry observed in the aldol reactions with benzaldehydes was explained by transition state model of the endocyclic (E)-enolate formed from the rigid 4-oxo-2-thioxoimidazolidine skeleton. Proton NMR and ROESY spectral analyses were carried out to identify the syn and anti conformations of the aldol diastereomers. Configurations of the enantiomers of the representative anti aldol product 3-(4-chlorophenyl)-5-[(4- chlorophenyl) hydroxy methyl]-5-methyl-4-oxo-2-thioxoimidazolidine was determined by single crystal XRD studies. The compounds were screened in vitro against prostate cancer cell lines, PC-3 and LNCaP and the most potent derivatives were identified.

Lithium perchlorate-induced electrophilic activation: one-pot synthesis of 3-aryl-2-thioxotetrahydropyrimidin-4-one derivatives from aryl isothiocyanates

A novel methodology for the synthesis of N-substituted-3-aryl-2-thioxotetrahydropyrimidin-4(1H)-one derivatives had been developed by the condensation of aryl isothiocyanates with β-amino esters using lithium perchlorate as a catalyst and triethylamine as a base. This strategy not only overcomes the disadvantages of the reported methods but also provides high yield of the product in short span of time by an easily workable procedure.

SELECTIVE ANDROGEN RECEPTOR MODULATORS, ANALOGS AND DERIVATIVES THEREOF AND USES THEREOF

This invention provides new compounds and uses thereof in treating a variety of diseases or conditions in a subject, including,inter alia, prostate cancer, muscle wasting diseases and/or disorders or a bone-related diseases and/or disorders.

Synthesis of oxazolidinedione derived bicalutamide analogs

The synthesis of chiral oxazolidinedione derived bicalutamide analogs has been discussed.