77533-17-6Relevant academic research and scientific papers
Novel inhibitors of bacterial virulence: Development of 5,6-dihydrobenzo[h]quinazolin-4(3H)-ones for the inhibition of group A streptococcal streptokinase expression
Yestrepsky, Bryan D.,Xu, Yuanxi,Breen, Meghan E.,Li, Xiaoqin,Rajeswaran, Walajapet G.,Ryu, Jenny G.,Sorenson, Roderick J.,Tsume, Yasuhiro,Wilson, Michael W.,Zhang, Wenpeng,Sun, Duxin,Sun, Hongmin,Larsen, Scott D.
, p. 1880 - 1897 (2013/05/08)
Resistance to antibiotics is an increasingly dire threat to human health that warrants the development of new modes of treating infection. We recently identified 1 (CCG-2979) as an inhibitor of the expression of streptokinase, a critical virulence factor in Group A Streptococcus that endows blood-borne bacteria with fibrinolytic capabilities. In this report, we describe the synthesis and biological evaluation of a series of novel 5,6-dihydrobenzo[h] quinazolin-4(3H)-one analogs of 1 undertaken with the goal of improving the modest potency of the lead. In addition to achieving an over 35-fold increase in potency, we identified structural modifications that improve the solubility and metabolic stability of the scaffold. The efficacy of two new compounds 12c (CCG-203592) and 12k (CCG-205363) against biofilm formation in Staphylococcus aureus represents a promising additional mode of action for this novel class of compounds.
1,3-Dihydro-3-(2-hydroxy-, 2-bromo- or 2-chloroethyl)-2H-isoindol-1-one derivatives
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, (2008/06/13)
Derivatives of 1,3-dihydro-3-(2-hydroxyethyl) -2H-isoindol-1-one are disclosed. The derivatives are useful for treating ulcers in a mammal and for preventing or decreasing the secretion or availability of excessive amounts of gastric or hydrochloric acid in a mammal suffering from hyperchlorhydria and/or associated conditions.
