1351185-76-6Relevant articles and documents
Design, synthesis and biological evaluation of novel 5-oxo-2-thioxoimidazolidine derivatives as potent androgen receptor antagonists
Ivachtchenko, Alexandre V.,Ivanenkov, Yan A.,Mitkin, Oleg D.,Vorobiev, Anton A.,Kuznetsova, Irina V.,Shevkun, Natalia A.,Koryakova, Angela G.,Karapetian, Ruben N.,Trifelenkov, Andrey S.,Kravchenko, Dmitry V.,Veselov, Mark S.,Chufarova, Nina V.
, p. 51 - 66 (2015/06/16)
A series of novel highly active androgen receptor (AR) antagonists containing spiro-4-(5-oxo-3-phenyl-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile core was designed based on the SAR studies available from the reported AR antagonists and in silico modeling. Within the series, compound (R)-6 (ONC1-13B) and its related analogues, including its active N-dealkylated metabolite, were found to be the most potent molecules with the target activity (IC50, androgen-sensitive human PCa LNCaP cells) in the range of 59-80 nM (inhibition of PSA production). The disclosed hits were at least two times more active than bicalutamide, nilutamide and enzalutamide within the performed assay. Several compounds were classified as partial agonists. Hit-compounds demonstrated benefit pharmacokinetic profiles in rats. Comparative SAR and 3D molecular docking studies were performed for the hit compounds elucidating the observed differences in the binding potency.
CYCLIC N,N'-DIARYLTHIOUREAS AND N,N'-DIARYLUREAS - ANDROGEN RECEPTOR ANTAGONISTS, ANTICANCER AGENT, METHOD FOR PREPARATION AND USE THEREOF
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Paragraph 0077, (2013/05/21)
The present invention relates to novel cyclic N,N′-diarylureas and N,N′-diarylthioureas—androgen receptor antagonists, anti-cancer agent, pharmaceutical composition, medicament, and method for treatment of cancerous diseases, among them prostate cancer. Cyclic N,N′-diarylthioureas or N,N′-diarylureas of the general formula 1, their optical (R)- and (S)-isomers and pharmaceutically acceptable salts thereof exhibiting properties of androgen receptor antagonists have been proposed, wherein: X represents oxygen or sulfur; m=0 or 1;R1 represents C1-C3alkyl;R2 and R3 represent hydrogen; orR2 and R3 together with C-atom they are attached to form C═O group; R4 and R5 represent hydrogen; orR4 represents hydrogen, R5 represents methyl; orR4 represents methyl, R5 represents CH2R6 group in which R6 represents C1-C3 alkoxycarbonyl, carboxyl, hydroxyl group optionally substituted with methyl or benzyl; orR4 and R5 together with C-atom they are attached to form 5- or 6-membered heterocycle comprising at least one oxygen atom or nitrogen atom optionally substituted with methyl; orR4 and R5 together with C-atom they are attached to form NH group.
