35524-89-1Relevant academic research and scientific papers
Synthesis and characterisation of [(en)2Co]3+ complexes coordinated by substituted thiourea ligands
Roecker, Lee,Aiyegbo, Mohammed,Al-Haddad, Aladdin,Fletcher, Emily,Kc, Ravi,Hurst, Jason,Lane, Timothy,Larsen, Ryan,Noinaj, Nicholas,Teh, Say Lee,Wade, Samuel K.,Parkin, Sean
, p. 944 - 951 (2013/09/12)
Substituted thiourea ligands bind in a bidentate manner forming a four-membered ring through the sulfur atom and a deprotonated thiourea nitrogen atom when reacted with [(en)2Co(OSO2CF3)2]+ in tetramethylene sulfone. Reaction of unsymmetrical ligands results in the formation of coordination isomers, some of which can be separated by column chromatography using Sephadex SPC-25. Coordination isomers are easily distinguishable based on visible and 1H NMR spectroscopy . Twelve para-substituted and one meta-substituted ligands were studied: N,N′-dibenzylthiourea (1a); N-(R)phenyl-N′-benzylthiourea R≤H (2a), NO2 (2b), CH3 (2c); N-(R)phenyl-N′-(R′)phenylthiourea R, R′: H, H (3a), H, CH3 (3b), OCH3, NO2 (3c), CH3, NO2 (3d); N-methyl-N′-(R)phenylthiourea R≤H (4a), CH3 (4b), OCH3 (4c), NO2 (4d), 3-CH3 (4e). The solid state structure (X-ray) of one isomer of Co-4a as its perchlorate salt confirms the coordination mode suggested by 1H NMR spectroscopy and shows that the Co-N bond trans to the coordinated thiourea sulfur induces a structural trans effect of 0.019A.
SAR studies of 4-pyridyl heterocyclic anilines that selectively induce autophagic cell death in von Hippel-Lindau-deficient renal cell carcinoma cells
Bonnet, Muriel,Flanagan, Jack U.,Chan, Denise A.,Lai, Edwin W.,Nguyen, Phuong,Giaccia, Amato J.,Hay, Michael P.
supporting information; experimental part, p. 3347 - 3356 (2011/07/09)
We recently identified a class of pyridyl aniline thiazoles (PAT) that displayed selective cytotoxicity for von Hippel-Lindau (VHL) deficient renal cell carcinoma (RCC) cells in vitro and in vivo. Structure-activity relationship (SAR) studies were used to develop a comparative molecular field analysis (CoMFA) model that related VHL-selective potency to the three-dimensional arrangement of chemical features of the chemotype. We now report the further molecular alignment-guided exploration of the chemotype to discover potent and selective PAT analogues. The contribution of the central thiazole ring was explored using a series of five- and six-membered ring heterocyclic replacements to vary the electronic and steric interactions in the central unit. We also explored a positive steric CoMFA contour adjacent to the pyridyl ring using Pd-catalysed cross-coupling Suzuki-Miyaura, Sonogashira and nucleophilic displacement reactions to prepare of a series of aryl-, alkynyl-, alkoxy- and alkylamino-substituted pyridines, respectively. In vitro potency and selectivity were determined using paired RCC cell lines: the VHL-null cell line RCC4 and the VHL-positive cell line RCC4-VHL. Active analogues selectively induced autophagy in RCC4 cells. We have used the new SAR data to further develop the CoMFA model, and compared this to a 2D-QSAR method. Our progress towards realising the therapeutic potential of this chemotype as a targeted cytotoxic therapy for the treatment of RCC by exploiting the absence of the VHL tumour suppressor gene is reported.
Synthesis and biological evaluation of 3-benzyl-1-methyl- and 1-methyl-3-phenyl-isothioureas as potential inhibitors of iNOS
Paesano, Nicola,Marzocco, Stefania,Vicidomini, Caterina,Saturnino, Carmela,Autore, Giuseppina,De Martino, Giovanni,Sbardella, Gianluca
, p. 539 - 543 (2007/10/03)
Novel benzyl- and phenyl-isothioureidic derivatives have been synthesised and evaluated as inhibitors of nitric oxide synthesis, induced in lipopolysaccharide (LPS)-activated J774.A1 macrophage cell line. The most potent iNOS inhibitor resulting was 1-methyl-3-phenyl-S-methyl isothiourea 5l.
