- Design, Synthesis, and Characterization of Novel Small Molecules as Broad Range Antischistosomal Agents
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Schistosomiasis is a major human parasitic disease afflicting more than 250 million people, historically treated with chemotherapies praziquantel or oxamniquine. Since oxamniquine is species-specific, killing Schistosoma mansoni but not other schistosome species (S. haematobium or S. japonicum) and evidence for drug resistant strains is growing, research efforts have focused on identifying novel approaches. Guided by data from X-ray crystallographic studies and Schistosoma worm killing assays on oxamniquine, our structure-based drug design approach produced a robust structure-activity relationship (SAR) program that identified several new lead compounds with effective worm killing. These studies culminated in the discovery of compound 12a, which demonstrated broad-species activity in killing S. mansoni (75%), S. haematobium (40%), and S. japonicum (83%).
- Rugel, Anastasia,Tarpley, Reid S.,Lopez, Ambrosio,Menard, Travis,Guzman, Meghan A.,Taylor, Alexander B.,Cao, Xiaohang,Kovalskyy, Dmytro,Chevalier, Frédéric D.,Anderson, Timothy J. C.,Hart, P. John,Loverde, Philip T.,McHardy, Stanton F.
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Read Online
- New tetrahydroisoquinoline-based P-glycoprotein modulators: Decoration of the biphenyl core gives selective ligands
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P-glycoprotein (P-gp, MDR1) is a membrane transporter expressed in several regions of our body. It plays a crucial defense role as it mediates the efflux of hundreds of potentially toxic substances. However, P-gp is one of the main causes of failure in ca
- Contino, Marialessandra,Guglielmo, Stefano,Perrone, Maria Grazia,Giampietro, Roberta,Rolando, Barbara,Carrieri, Antonio,Zaccaria, Daniele,Chegaev, Konstantin,Borio, Vanessa,Riganti, Chiara,Zabielska-Koczywas, Katarzyna,Colabufo, Nicola A.,Fruttero, Roberta
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supporting information
p. 862 - 869
(2018/05/31)
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- Structure-Based Drug Design of Potent Pyrazole Derivatives against Rhinovirus Replication
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Rhinoviruses (RVs) have been linked to exacerbations of many pulmonary diseases, thus increasing morbidity and/or mortality in subjects at risk. Unfortunately, the wide variety of RV genotypes constitutes a major hindrance for the development of Rhinovirus replication inhibitors. In the current investigation, we have developed a novel series of pyrazole derivatives that potently inhibit the Rhinovirus replication. Compounds 10e and 10h behave as early stage inhibitors of Rhinovirus infection with a broad-spectrum activity against RV-A and RV-B species (EC50 0.1 μM). We also evaluate the dynamics of the emerging resistance of these promising compounds and their in vitro genotoxicity. Molecular docking experiments shed light on the pharmacophoric elements interacting with residues of the drug-binding pocket.
- Da Costa, Laurène,Scheers, Els,Coluccia, Antonio,Casulli, Adriano,Roche, Manon,Di Giorgio, Carole,Neyts, Johan,Terme, Thierry,Cirilli, Roberto,La Regina, Giuseppe,Silvestri, Romano,Mirabelli, Carmen,Vanelle, Patrice
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p. 8402 - 8416
(2018/09/18)
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- FUSED 1,4-DIHYDRODIOXIN DERIVATIVES AS INHIBITORS OF HEAT SHOCK TRANSCRIPTION FACTOR 1
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The present invention relates to compounds of formula I wherein A1, A2 R4 and Q are as defined herein. The compounds of the present invention are inhibitors of heat shock factor 1 (HSF1). In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.
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Paragraph 00300
(2015/04/22)
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- Debundling, selection and release of SWNTs using fluorene-based photocleavable polymers
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Photocleavable polymers based on 9,9-dialkylfluorene backbone and o-nitrobenzylether were designed and synthesized to obtain stable (n,m) enriched suspensions of semiconducting SWNTs in toluene. Photoirradiation of the suspensions triggered the precipitat
- Lemasson, Fabien,Tittmann, Jana,Hennrich, Frank,Stuerzl, Ninette,Malik, Sharali,Kappes, Manfred M.,Mayor, Marcel
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supporting information; experimental part
p. 7428 - 7430
(2011/08/08)
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- Novel bicyclic sulfonamide derivatives which are L-CPT1 inhibitors
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The invention is concerned with novel heterobicyclic derivatives of formula (I) wherein R1, R2, R3, R4, R5, R6, V, W, X and Y are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds inhibit L-CPT1 and can be used as medicaments.
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Page/Page column 40
(2010/11/28)
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- QUINAZOLINES FOR PDK1 INHIBITION
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The invention provides novel quinazoline compounds that are inhibitors of PDK1. Also provided are pharmaceutical compositions including the compounds, and methods of treating proliferative diseases, such as cancers, with the compounds or compositions.
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Page/Page column 333
(2008/06/13)
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