90357-53-2Relevant articles and documents
Synthesis, biological evaluation and X-ray analysis of bicalutamide sulfoxide analogues for the potential treatment of prostate cancer
Kandil, Sahar B.,Kariuki, Benson M.,McGuigan, Christopher,Westwell, Andrew D.
supporting information, (2021/02/16)
The androgen receptor (AR) is a pivotal target for the treatment of prostate cancer (PC) even when the disease progresses toward androgen-independent or castration-resistant forms. In this study, a series of sulfoxide derivatives were prepared and their antiproliferative activity evaluated in vitro against four different human prostate cancer cell lines (22Rv1, DU-145, LNCaP and VCap). Bicalutamide and enzalutamide were used as positive controls. Compound 28 displayed significant enhancement in anticancer activity across the four PC cell lines with IC50 = 9.09 – 31.11 μM compared to the positive controls: bicalutamide (IC50 = 45.20 –51.61 μM) and enzalutamide (IC50 = 11.47 – 53.04 μM). Sulfoxide derivatives of bicalutamide were prepared efficiently from the corresponding sulfides using only one equivalent of mCPBA, limiting the reaction time to 15–30 min and maintaining the temperature at 0 °C. Interestingly, three pairs of sulfoxide diastereomers were separated and NMR comparison of their diastereotopic methylene (CH2) group is presented. X-ray diffraction crystal structure analysis provided relative configuration assignment at the chiral sulfur and carbon centres. Molecular modelling study of the four diastereoisomers of compound 28 is described.
A new series of bicalutamide, enzalutamide and enobosarm derivatives carrying pentafluorosulfanyl (SF5) and pentafluoroethyl (C2F5) substituents: Improved antiproliferative agents against prostate cancer
Pertusati, Fabrizio,Ferla, Salvatore,Bassetto, Marcella,Brancale, Andrea,Khandil,Westwell, Andrew D.,McGuigan, Christopher
supporting information, p. 1 - 14 (2019/07/10)
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.
Preparation method of bicalutamide epoxy intermediate
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Paragraph 0016; 0018-0022, (2019/03/28)
The invention relates to synthesis of chemical drugs, and relates to a preparation method of a bicalutamide epoxy intermediate, in particular to a preparation method of N-[4-cyano-3-(trifluoromethyl)phenyl]-1,2-epoxy-2-methylpropionamide. According to the method, lower fatty acid ester serves as a solvent, 4-cyano-3-(trifluoromethyl)aniline as a raw material is subjected to two-step reaction of methyl propene acylation and epoxidation to generate N-[4-cyano-3-(trifluoromethyl)phenyl]-2,3-epoxy-2-methylpropionamide, an acid-binding agent is used as a catalyst in methyl propene acylation reaction, and hydrogen peroxide serves as a peroxide source in epoxidation reaction. According to the method, the preparation and reaction conditions are mild, the use of trichloroethane and diethyl ether with extremely high danger is avoided, the intermediate product can be directly applied to the epoxidation reaction without separation and refining, the operation is convenient, and the working time isrelatively short.
