698397-76-1Relevant articles and documents
Synthesis and biological evaluation of N-acylated tyramine sulfamates containing C–F bonds as steroid sulfatase inhibitors
Da?ko, Mateusz,Rachon, Janusz,Mas?yk, Maciej,Kubiński, Konrad,Demkowicz, Sebastian
, p. 156 - 161 (2017)
Steroid sulfatase (STS) is responsible for the hydrolysis of biologically inactive sulfated steroids into their active un-sulfated forms and promotes the growth of various hormone-dependent cancers (e.g., breast cancer). Therefore, the STS enzyme is a promising therapeutic target for the treatment of steroid-sensitive cancers. Herein, we report the synthesis and biological evaluation of sulfamate analogs as potential STS inhibitors based on N-acylated tyramines that contain C–F bonds. The inhibitory effects of the analogs were tested using STS isolated from human placenta. Of the analogs tested, 4-(2-perfluoroundecanoylaminoethyl)-phenyl sulfamate, 5r, demonstrated the greatest inhibitory effect, with an IC50 value of 2.18?μm (IC50 value of 2.13?μm for coumarin-7-O-sulfamate was used as a reference). These findings were supported by the results our computational analyses performed using molecular docking techniques.
Preparation method of N-phenylacetyl-2-hydroxymethylpyrrolidine-2-formamide and medicinal application of N-phenylacetyl-2-hydroxymethylpyrrolidine-2-formamide
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Paragraph 0045; 0046, (2021/01/12)
The invention discloses N-phenylacetyl-2-hydroxymethylpyrrolidine-2-formamide as shown in a general formula (I), a preparation method of the compound, a new application of the compound and a pharmaceutical composition containing the compound in the aspect of inhibiting neuroglial cell inflammation. Wherein R1/R2 is equal to H, F, CF3 or OCF3.
Synthesis and biological evaluation of fluorinated N-benzoyl and N-phenylacetoyl derivatives of 3-(4-aminophenyl)-coumarin-7-O-sulfamate as steroid sulfatase inhibitors
Da?ko, Mateusz,Przyby?owska, Maja,Rachon, Janusz,Mas?yk, Maciej,Kubiński, Konrad,Misiak, Majus,Sk?adanowski, Andrzej,Demkowicz, Sebastian
, p. 79 - 87 (2017/02/05)
In the present work, we report convenient methods for the synthesis of 3-(4-aminophenyl)-coumarin-7-O-sulfamate derivatives N-acylated with fluorinated analogues of benzoic or phenylacetic acid as steroid sulfatase (STS) inhibitors. The design of these potential STS inhibitors was supported by molecular modeling techniques. Additionally, computational docking methods were used to determine the binding modes of the synthesized inhibitors and to identify potential interactions between inhibitors and amino acid residues located in the active site of STS. The inhibitory effects of the synthesized compounds were tested on STS isolated from human placenta and against estrogen receptor-(ER)-positive MCF-7 and T47D cells, as well as ER-negative MDA-MB-231 and SkBr3 cancer cell lines. In the course of our investigation, compounds 6c and 6j demonstrated the highest inhibitory effect in enzymatic STS assays, both with IC50values of 0.18?μM (the IC50value of coumarin-7-O-sulfamate is 1.38?μM, used as a reference). Compound 6j exhibited the highest potency against the MCF-7 and T47D cell lines (15.9?μM and 8.7?μM, respectively). The GI50values of tamoxifen (used as a reference) were 6.8; 10.6; 15.1; 12.5?μM against MCF-7, T47D, MDA-MB-231 and SkBr3 cancer cell lines, respectively. Despite the slightly lower activity of compounds 1 and 2 (both in enzymatic and cell-based experiments) compared to 6g and 6j, analogues 1 and 2 proved to selectively inhibit the growth of ER- and PR-positive cell lines.
