- Recyclable palladium-catalyzed carbonylative annulation of 2-iodoanilines with acid anhydrides: A practical synthesis of 2-alkylbenzoxazinones
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A highly efficient heterogeneous palladium-catalyzed carbonylative annulation of 2-iodoanilines and acid anhydrides has been developed. The reaction proceeds effectively in toluene using N,N-diisopropylethylamine (DiPEA) as the base at 100 °C under 2 bar of CO and provides a novel, general, and practical method for the assembly of a wide variety of 2-alkylbenzoxazinones with high functional group tolerance and good to excellent yields. This supported palladium complex can be readily separated from the product and recovered by a simple filtration of the reaction solution and reused up to seven times with almost consistent catalytic efficiency.
- Zhou, Zebiao,Huang, Bin,Cai, Mingzhong
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p. 3150 - 3163
(2021/08/30)
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- Quinazolinone derivatives as inhibitors of homologous recombinase RAD51
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RAD51 is a vital component of the homologous recombination DNA repair pathway and is overexpressed in drug-resistant cancers, including aggressive triple negative breast cancer (TNBC). A proposed strategy for improving therapeutic outcomes for patients is through small molecule inhibition of RAD51, thereby sensitizing tumor cells to DNA damaging irradiation and/or chemotherapy. Here we report structure-activity relationships for a library of quinazolinone derivatives. A novel RAD51 inhibitor (17) displays up to 15-fold enhanced inhibition of cell growth in a panel of TNBC cell lines compared to compound B02, and approximately 2-fold increased inhibition of irradiation-induced RAD51 foci formation. Additionally, compound 17 significantly inhibits TNBC cell sensitivity to DNA damage, implying a potentially targeted therapy for cancer treatment.
- Ward, Ambber,Dong, Lilong,Harris, Jonathan M.,Khanna, Kum Kum,Al-Ejeh, Fares,Fairlie, David P.,Wiegmans, Adrian P.,Liu, Ligong
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supporting information
p. 3096 - 3100
(2017/06/13)
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- Structure-Activity Relationship for the 4(3H)-Quinazolinone Antibacterials
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We recently reported on the discovery of a novel antibacterial (2) with a 4(3H)-quinazolinone core. This discovery was made by in silico screening of 1.2 million compounds for binding to a penicillin-binding protein and the subsequent demonstration of antibacterial activity against Staphylococcus aureus. The first structure-activity relationship for this antibacterial scaffold is explored in this report with evaluation of 77 variants of the structural class. Eleven promising compounds were further evaluated for in vitro toxicity, pharmacokinetics, and efficacy in a mouse peritonitis model of infection, which led to the discovery of compound 27. This new quinazolinone has potent activity against methicillin-resistant (MRSA) strains, low clearance, oral bioavailability and shows efficacy in a mouse neutropenic thigh infection model.
- Bouley, Renee,Ding, Derong,Peng, Zhihong,Bastian, Maria,Lastochkin, Elena,Song, Wei,Suckow, Mark A.,Schroeder, Valerie A.,Wolter, William R.,Mobashery, Shahriar,Chang, Mayland
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p. 5011 - 5021
(2016/06/13)
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- Compounds for modulating TRPV3 function
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The present application relates to compounds and methods for treating pain and other conditions related to TRPV3.
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Page/Page column 145
(2016/11/24)
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- Compounds for modulating TRPV3 function
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The present application relates to compounds and methods for treating pain and other conditions related to TRPV3.
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Page/Page column 45; 46
(2010/11/28)
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