218943-57-8Relevant articles and documents
MACROCYCLIC COMPLEXES OF ALPHA-EMITTING RADIONUCLIDES AND THEIR USE IN TARGETED RADIOTHERAPY OF CANCER
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Paragraph 0246-0247, (2020/06/08)
The present technology provides compounds as well as compositions including such compounds useful in targeted radiotherapy of cancer and/or mammalian tissue overexpressing prostate specific membrane antigen (“PSMA”) where the compounds are represented by
Visible-Light Photoredox-Catalyzed and Copper-Promoted Trifluoromethoxylation of Arenediazonium Tetrafluoroborates
Yang, Shaoqiang,Chen, Miao,Tang, Pingping
supporting information, p. 7840 - 7844 (2019/05/15)
We report the development of photoredox-catalyzed and copper-promoted trifluoromethoxylation of arenediazonium tetrafluoroborates, with trifluoromethyl arylsulfonate (TFMS) as the trifluoromethoxylation reagent. This new method takes advantage of visible-light photoredox catalysis to generate the aryl radical under mild conditions, combined with copper-promoted selective trifluoromethoxylation. The reaction is scalable, tolerates a wide range of functional groups, and proceeds regioselectively under mild reaction conditions. Furthermore, mechanistic studies suggested that a Cs[Cu(OCF3)2] intermediate might be generated during the reaction.
Design of a True Bivalent Ligand with Picomolar Binding Affinity for a G Protein-Coupled Receptor Homodimer
Pulido, Daniel,Casadó-Anguera, Verònica,Pérez-Benito, Laura,Moreno, Estefanía,Cordomí, Arnau,López, Laura,Cortés, Antoni,Ferré, Sergi,Pardo, Leonardo,Casadó, Vicent,Royo, Miriam
, p. 9335 - 9346 (2018/10/24)
Bivalent ligands have emerged as chemical tools to study G protein-coupled receptor dimers. Using a combination of computational, chemical, and biochemical tools, here we describe the design of bivalent ligand 13 with high affinity (KDB1 = 21 pM) for the dopamine D2 receptor (D2R) homodimer. Bivalent ligand 13 enhances the binding affinity relative to monovalent compound 15 by 37-fold, indicating simultaneous binding at both protomers. Using synthetic peptides with amino acid sequences of transmembrane (TM) domains of D2R, we provide evidence that TM6 forms the interface of the homodimer. Notably, the disturber peptide TAT-TM6 decreased the binding of bivalent ligand 13 by 52-fold and had no effect on monovalent compound 15, confirming the D2R homodimer through TM6 ex vivo. In conclusion, by using a versatile multivalent chemical platform, we have developed a precise strategy to generate a true bivalent ligand that simultaneously targets both orthosteric sites of the D2R homodimer.
Discovery of Potent Human Glutaminyl Cyclase Inhibitors as Anti-Alzheimer’s Agents Based on Rational Design
Hoang, Van-Hai,Tran, Phuong-Thao,Cui, Minghua,Ngo, Van T. H.,Ann, Jihyae,Park, Jongmi,Lee, Jiyoun,Choi, Kwanghyun,Cho, Hanyang,Kim, Hee,Ha, Hee-Jin,Hong, Hyun-Seok,Choi, Sun,Kim, Young-Ho,Lee, Jeewoo
, p. 2573 - 2590 (2017/04/03)
Glutaminyl cyclase (QC) has been implicated in the formation of toxic amyloid plaques by generating the N-terminal pyroglutamate of β-amyloid peptides (pGlu-Aβ) and thus may participate in the pathogenesis of Alzheimer’s disease (AD). We designed a library of glutamyl cyclase (QC) inhibitors based on the proposed binding mode of the preferred substrate, Aβ3E?42. An in vitro structure-activity relationship study identified several excellent QC inhibitors demonstrating 5- to 40-fold increases in potency compared to a known QC inhibitor. When tested in mouse models of AD, compound 212 significantly reduced the brain concentrations of pyroform Aβ and total Aβ and restored cognitive functions. This potent Aβ-lowering effect was achieved by incorporating an additional binding region into our previously established pharmacophoric model, resulting in strong interactions with the carboxylate group of Glu327 in the QC binding site. Our study offers useful insights in designing novel QC inhibitors as a potential treatment option for AD.
Pyrimidinone Derivatives as Antimalarial Agents
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, (2015/07/15)
The invention relates to novel pyrimidinone-based heterocyclic compounds which are parasite growth inhibitors, having the general formula (I) in which Y is a morpholine chosen from three bridged morpholines, L is a bond or a linker, n=0 or 1 and R2 is a methyl group when n=0 and a hydrogen atom when n=1. Process for the preparation thereof and therapeutic use thereof.
PYRIMIDINONE DERIVATIVES AS ANTIMALARIAL AGENTS
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, (2014/01/09)
The invention relates to novel pyrimidinone-based heterocyclic compounds which are parasite growth inhibitors, having the general formula (I) in which Y is a morpholine chosen from three bridged morpholines, L is a bond or a linker, n = 0 or 1 and R2 is a methyl group when n = 0 and a hydrogen atom when n = 1. Process for the preparation thereof and therapeutic use thereof.
CONTRAST AGENTS ENDOWED WITH HIGH RELAXIVITY
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Page/Page column 78, (2008/06/13)
The present invention relates to a novel class of paramagnetic ion-based contrast agents of formula (I), wherein a chelating backbone moiety is highly functionalized by the presence of one or more polyhdroxylated chain, that show a pharmacokinetic profile analogous to that of the commonly used T1-general extravascular agents (NSA) but are further characterized by a higher relaxivity.
Derivatives of 2-(iminomethyl)amino-phenyl, their preparation, their use as medicaments and the pharmaceutical compositions containing them
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Page column 87, (2008/06/13)
A compound selected from the group consisting of a compound of the formula wherein A is selected from the group consisting of and the other substituents are defined in the specification having an inhibitory activity of NO-synthase enzymes producing nitrogen mono-oxide and/or an activity which traps the reactive oxygen species.