112894-44-7Relevant academic research and scientific papers
Diarylsulfonylureas for use in treating secretory diarrhea
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, (2008/06/13)
This invention provides methods of treating secretory diarrhea or cystic fibrosis in a mammal which comprises administering to a mammal in need thereof an effective amount of diarylsulfonylurea. This invention also describes specific diarylsulfonylureas f
Antitumor compositions and methods of treatment
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, (2008/06/13)
This invention provides the use of certain tetra-substituted imidazolidin-2-one derivatives in the treatment of susceptible neoplasms in mammals. Also provided are certain novel tetra-substituted imidazolidin-2-one derivatives and pharmaceutical formulati
Novel agents effective against solid tumors: The diarylsulfonylureas. Synthesis, activities, and analysis of quantitative structure-activity relationships
Howbert,Grossman,Crowell,Rieder,Harper,Kramer,Tao,Aikins,Poore,Rinzel,Grindey,Shaw,Todd
, p. 2393 - 2407 (2007/10/02)
A series of diarylsulfonylureas with exceptionally broad-spectrum activity against syngeneic rodent solid tumors in vivo is described. Their discovery resulted from a program dedicated to in vivo screening for novel oncolytics in solid tumor models, rather than traditional ascites leukemia models. The structures, oral efficacy, side-effect profile, and mechanism of action of these sulfonylureas appear to be distinct from previously known classes of oncolytics. An extensive series of analogues was prepared to probe structure-activity relationships (SAR), with particular focus on the substituent patterns of each aryl domain. Quantitative analysis of these substituent SARs, using the method of cluster significance analysis, showed the lipophilicity of the substituents to be the dominant determinant of activity. One compound from the series, LY186641 (104, sulofenur), has progressed to Phase I clinical trials as an antitumor drug.
