18792-01-3Relevant academic research and scientific papers
Role of Substituents at 3-position of Thienylethynyl Spacer on Electronic Properties in Diruthenium(II) Organometallic Wire-like Complexes
Roy, Sourav Saha,Chowdhury, Sabyasachi Roy,Mishra, Sabyashachi,Patra, Sanjib K.
supporting information, p. 3304 - 3313 (2020/09/09)
A series of organometallic complexes [Cl(dppe)2Ru?C≡C-(3-R?C4H2S)-C≡C?Ru(dppe)2Cl] (3-R-C4H2S=3-substituted thienyl moiety; R=?H, ?C2H5, ?C3H7, ?C4H9, ?C6H13, ?OMe, ?CN in 5 a–5 g respectively) have been synthesized by systematic variation of 3-substituents at the thienylethynyl bridging unit. The diruthenum(II) wire-like complexes (5 a–5 g) have been achieved by the reaction of thienylethynyl bridging units, HC≡C-(3-R-C4H2S)-C≡CH (4 a–4 g) with cis-[Ru(dppe)2Cl2]. The wire-like diruthenium(II) complexes undergo two consecutive electrochemical oxidation processes in the potential range of 0.0 - 0.8 V. Interestingly, the wave separation between the two redox waves is greatly influenced by the substituents at the 3-position of the thienylethynyl. Thus, the substitution on 3-position of the thienylethynyl bridging unit plays a pivotal role for tuning the electronic properties. To understand the electronic behavior, density functional theory (DFT) calculations of the selected diruthenium wire-like complexes (5 a–5 e) with different alkyl appendages are performed. The theoretical data demonstrate that incorporation of alkyl groups to the thienylethynyl entity leaves unsymmetrical spin densities, thus affecting the electronic properties. The voltammetric features of the other two Ru(II) alkynyl complexes 5 f and 5 g (with ?OMe and ?CN group respectively) show an apparent dependence on the electronic properties. The electronic properties in the redox conjugate, (5 a+) with Kc of 3.9×106 are further examined by UV-Vis-NIR and FTIR studies, showing optical responses in NIR region along with changes in “?Ru?C≡C?“ vibrational stretching frequency. The origin of the observed electronic transition has been assigned based on time-dependent DFT (TDDFT) calculations.
Discovery of small-molecule inhibitors selectively targeting the DNA-binding domain of the human androgen receptor
Li, Huifang,Ban, Fuqiang,Dalal, Kush,Leblanc, Eric,Frewin, Kate,Ma, Dennis,Adomat, Hans,Rennie, Paul S.,Cherkasov, Artem
supporting information, p. 6458 - 6467 (2014/10/15)
The human androgen receptor (AR) is considered as a master regulator in the development and progression of prostate cancer (PCa). As resistance to clinically used anti-AR drugs remains a major challenge for the treatment of advanced PCa, there is a pressing need for new anti-AR therapeutic avenues. In this study, we identified a binding site on the DNA binding domain (DBD) of the receptor and utilized virtual screening to discover a set of micromolar hits for the target. Through further exploration of the most potent hit (1), a structural analogue (6) was identified demonstrating 10-fold improved anti-AR potency. Further optimization resulted in a more potent synthetic analogue (25) with anti-AR potency comparable to a newly FDA-approved drug Enzalutamide. Site-directed mutagenesis demonstrated that the developed inhibitors do interact with the intended target site. Importantly, the AR DBD inhibitors could effectively inhibit the growth of Enzalutamide-resistant cells as well as block the transcriptional activity of constitutively active AR splice variants, such as V7.
THIOPHENE DERIVATIVE
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Page/Page column 17, (2012/03/26)
The present invention provides a compound represented by the formula (I) or its salt, solvate, or physiologically functional derivative; and a pharmaceutical composition which is useful for treatment or prevention of conditions or disorders having sensitivity to selective androgen receptor modulation, the composition comprising the above-described compound; among others:
Pyridylfuran and pyridylthiophene compounds
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, (2008/06/13)
A compound of the formula: and its pharmaceutically effective salts, wherein R1 and R2 are independently selected from the following: (a) hydrogen, halo, R5-, C2-6 alkenyl, C2-6 alkynyl, hydroxy-R5-, R5-O-R5-, or the like; (b) Ar-, Ar-R5-, Ar-C2-6 alkenyl, Ar-C2-6 alkynyl, Ar-O-, Ar-O-R5- or the like; (c) R5-C(O)-, -NO2, cyano, NH2-C(O)-, R5-NH-C(O)-, (R5)2-N-C(O)-, Ar-C(O)- or the like; and (d) R5-C(O)-NH-, Ar-C(O)-NH- or the like; wherein Ar is optionally substituted aryl or heteroaryl such as phenyl and pyridyl; and wherein R5 is optionally halo-substituted C1-6 alkyl; R3 is selected from the following: (e) cyano, formyl, tetrazolyl, triazolyl, imidazolyl, oxazolyl, thiazolyl, R5-C(O)-, C2-6 alkenyl-C(O)-, C2-6 alkynyl-C(O)-, R5-C(O)-R5-, or the like; (f) R5-C(O)-NH-, Ar-C(O)-NH-, or the like; (g) R5-S-, R5-S(O)-, R5-NH-S(O)2-, or the like; and (h) Ar-C(O)-, Ar-R5-C(O)-, Ar-C2-6 alkenylene-C(O)- or the like; or two of R1, R2 and R3 together form a group of the formula -A1-B1-A2- or -A1-B1-A3-B2-A2- such as cyclic alkyl optionally substituted with oxo; R4 is hydrogen, halo, R5-C(O)- and the like; X is O, S, S(O) or S(O)2; m is 0, 1, 2, 3 or 4. The present invention also provides processes for the preparation thereof, the use thereof in treating cytokine mediated diseases and/or cell adhesion molecule (CAM) mediated diseases and pharmaceutical compositions for use in such therapy.
