- ANDROGEN RECEPTOR ANTAGONISTS
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Compounds that inhibit the androgen receptor, pharmaceutical compositions comprising one or more of the compounds, as well as methods of treating cancer using such compounds are described.
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- Easy-To-Synthesize Spirocyclic Compounds Possess Remarkable in Vivo Activity against Mycobacterium tuberculosis
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Society urgently needs new, effective medicines for the treatment of tuberculosis. To kick-start the required hit-to-lead campaigns, the libraries of pharmaceutical companies have recently been evaluated for starting points. The GlaxoSmithKline (GSK) library yielded many high-quality hits, and the associated data were placed in the public domain to stimulate engagement by the wider community. One such series, the spiro compounds, are described here. The compounds were explored by a combination of traditional in-house research and open source methods. The series benefits from a particularly simple structure and a short associated synthetic chemistry route. Many members of the series displayed striking potency and low toxicity, and highly promising in vivo activity in a mouse model was confirmed with one of the analogues. Ultimately the series was discontinued due to concerns over safety, but the associated data remain public domain, empowering others to resume the series if the perceived deficiencies can be overcome.
- Guardia, Ana,Baiget, Jessica,Cacho, Mónica,Pérez, Arancha,Ortega-Guerra, Montserrat,Nxumalo, Winston,Khanye, Setshaba D.,Rullas, Joaquín,Ortega, Fátima,Jiménez, Elena,Pérez-Herrán, Esther,Fraile-Gabaldón, María Teresa,Esquivias, Jorge,Fernández, Raquel,Porras-De Francisco, Esther,Encinas, Lourdes,Alonso, Marta,Giordano, Ilaria,Rivero, Cristina,Miguel-Siles, Juan,Osende, Javier G.,Badiola, Katrina A.,Rutledge, Peter J.,Todd, Matthew H.,Remui?án, Modesto,Alemparte, Carlos
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p. 11327 - 11340
(2019/01/08)
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- Discovery and structure-activity relationships of pyrrolone antimalarials
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In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of one of the hits from this process, TDR32750 (8a), which showed potent activity against Plasmodium falciparum K1 (EC50 ~ 9 nM), good selectivity (>2000-fold) compared to a mammalian cell line (L6), and significant activity against a rodent model of malaria when administered intraperitoneally. Structure-activity relationship studies have indicated ways in which the molecule could be optimized. This compound represents an exciting start point for a drug discovery program for the development of a novel antimalarial.
- Murugesan, Dinakaran,Mital, Alka,Kaiser, Marcel,Shackleford, David M.,Morizzi, Julia,Katneni, Kasiram,Campbell, Michael,Hudson, Alan,Charman, Susan A.,Yeates, Clive,Gilbert, Ian H.
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p. 2975 - 2990
(2013/05/23)
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- NOVEL QUINOLINIUM SALTS AND DERIVATIVES
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The present invention relates generally to the synthesis of novel quinolinium salts and derivative compounds. Such salts and compounds are useful for inhibiting the growth of cancer cells.
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Page/Page column 47
(2008/06/13)
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