78790-82-6Relevant academic research and scientific papers
4-Pyridylanilinothiazoles that selectively target von Hippel - Lindau deficient renal cell carcinoma cells by inducing autophagic cell death
Hay, Michael P.,Turcotte, Sandra,Flanagan, Jack U.,Bonnet, Muriel,Chan, Denise A.,Sutphin, Patrick D.,Nguyen, Phuong,Giaccia, Amato J.,Denny, William A.
supporting information; experimental part, p. 787 - 797 (2010/07/05)
Renal cell carcinomas (RCC) are refractory to standard therapy with advanced RCC having a poor prognosis; consequently treatment of advanced RCC represents an unmet clinical need. The von Hippel-Lindau (VHL) tumor suppressor gene is mutated or inactivated in a majority of RCCs. We recently identified a 4-pyridyl-2-anilinothiazole (PAT) with selective cytotoxicity against VHL-deficient renal cells mediated by induction of autophagy and increased acidification of autolysosomes. We report exploration of structure-activity relationships (SAR) around this PAT lead. Analogues with substituents on each of the three rings, and various linkers between rings, were synthesized and tested in vitro using paired RCC4 cell lines. A contour map describing the relative spatial contributions of different chemical features to potency illustrates a region, adjacent to the pyridyl ring, with potential for further development. Examples probing this domain validated this approach and may provide the opportunity to develop this novel chemotype as a targeted approach to the treatment of RCC. 2009 American Chemical Society.
HETEROARYL COMPOUNDS, COMPOSITIONS, AND METHODS OF USE IN CANCER TREATMENT
-
, (2009/10/22)
Provided herein are novel heteroaryl compounds, compositions comprising the compounds, and methods of treatment or prevention comprising administration of the compounds. The compounds are effective in the targeting of cells defective in the von Hippel-Lindau gene and in inducing autophagic cell death. The methods are directed to treating or preventing diseases such as cancer, and in particular cancers resulting from von Hippel-Lindau disease. The compounds of the invention may be administered in combination with another therapeutic agent.
Chemoselective Reactions of 3-Chloroisonicotinonitrile
LaMattina, John L.,Taylor, Richard L.
, p. 4179 - 4182 (2007/10/02)
Chemoselective reactions of 3-chloroisonicotinonitrile (1) with nucleophiles are described.Treatment of 1 with sodium methoxide/methanol results in formation of the imino ether, which can be further elaborated into a triazole ring.However, when 1 is react
ETUDE DES ortho-METALLATIONS REGIOSELECTIVES DE LA CHLORO-3 PYRIDINE PAR DES ORGANOLITHIENS ET DES AMIDURES DE LITHIUM; EFFET D'ORIENTATION PAR LE SOLVANT, APPLICATIONS A LA SYNTHESE
Marsais, Francis,Breant, Patrice,Ginguene, Alain,Queguiner, Guy
, p. 139 - 147 (2007/10/02)
Lithium dialkylamides metalate 3-chloropyridine with excellent regioselectivity at position 4.This reaction occurs in THF solution at -60 deg C and it leads to various 3,4-disubstituted pyridines in good yields.This regioselectivity is completely changed in ether solution by using the butyllithium-TMEDA complex.In that case position 2 is metallated and 2,3-disubstituted pyridines are obtained.
