- Clickable prodrugs bearing potent and hydrolytically cleavable nicotinamide phosphoribosyltransferase inhibitors
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Purpose: Our previous study indicated that carborane containing small-molecule 1-(hydroxymethyl)-7-(4′-(trans-3″-(3′″-pyridyl)acrylamido)butyl)-1,7-dicarbadodecaborane (hm-MC4-PPEA), was a potent inhibitor of nicotinamide phosphoribosyltransferase (Nampt)
- Sadrerafi, Keivan,Mason, Emilia O.,Lee, Mark W.
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Read Online
- Synthesis and antitumor activity of DNA binding cationic porphyrin-platinum(II) complexes
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A new series of DNA binding 5,10,15-tri(N-methyl-4-pyridiniumyl)porphyrin (TrisMPyP)-platinum(II) conjugates was synthesized, in which different spacer ligands were used for appropriate coordination to platinum(II) complexes. Compound 9b exhibited in vivo antitumor activity (T/C%, 294) superior to cisplatin (T/C%, 184) against the leukemia L1210 cell line.
- Song, Rita,Kim, Yeong-Sang,Lee, Chong Ock,Sohn, Youn Soo
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Read Online
- Gold nanoparticles coated with semi-fluorinated oligo(ethylene glycol) produce sub-100 nm nanoparticle vesicles without templates
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Gold nanoparticles (NPs) with diameters of 5, 10, and 20 nm coated with semifluorinated oligo(ethylene glycol) ligands were formed into sub-100 nm hollow NP assemblies (NP vesicles) in THF without the use of a template. The NP vesicles maintained their st
- Niikura, Kenichi,Iyo, Naoki,Higuchi, Takeshi,Nishio, Takashi,Jinnai, Hiroshi,Fujitani, Naoki,Ijiro, Kuniharu
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Read Online
- Stable pillar[5]arene-based pseudo[1]rotaxanes formed in polar solution
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Mono-alkyl-functionalized pillar[5]arenes P1, P2, and P3 were synthesized by click reaction, which exhibited different self-assembly behavior in polar solvent DMSO. Stable pseudo[1]rotaxane was formed by the self-complexation from P1 or P2, whereas, concentration-dependent pseudorotaxane structures were generated by P3 which bearing more flexible side chain. Interestingly, the obtained pseudo[1]rotaxanes exhibited a dynamic fast assembly process upon adding NaBF4, resulting in the formation of Na+-induced pseudorotaxanes.
- Wu, Xuan,Gao, Lei,Sun, Junzhao,Hu, Xiao-Yu,Wang, Leyong
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Read Online
- Synthesis of optically active 1,1′-binaphthyl-phthalocyanines linked via a crown ether unit
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Novel optically active metal and metal-free phthalocyanines, substituted with 1,1′-binaphthyl crown ether units, have been synthesized and characterized.
- Liu, Hong-Wei,Chen, Chuan-Fu,Ai, Min,Gong, Ai-Jun,Jiang, Jing,Xi, Fu
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Read Online
- Pegylated triarylmethanes: Synthesis, antimicrobial activity, anti-proliferative behavior and in silico studies
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We describe herein the synthesis, characterization and biological studies of novel PEGylated triarylmethanes. Non-symmetrical and symmetrical triarylmethanes series have been synthesized by Friedel-Crafts hydroxyalkylation or directly from bisacodyl respectively followed by a functionalization with PEG fragments in order to increase bioavailability and biological effectiveness. The antimicrobial activity was investigated against Gram-positive and Gram-negative foodborne pathogens and against Candida albicans, an opportunistic pathogenic yeast. The anti-biocidal activity was also studied using Staphylococcus aureus as a reference bacterium. Almost all PEGylated molecules displayed an antifungal activity comparable with fusidic acid with MIC values ranging from 6.25 to 50 μg/mL. Compounds also revealed a promising antibiofilm activity with biofilm eradication percentages values above 80% for the best molecules (compounds 4d and 7). Compounds 7 and 8b showed a modest antiproliferative activity against human colorectal cancer cell lines HT-29. Finally, in silico molecular docking studies revealed DHFR and DNA gyrase B as potential anti-bacterial targets and in silico predictions of ADME suggested adequate drug-likeness profiles for the synthetized triarylmethanes.
- Abdmouleh, Fatma,Ali, Mamdouh Ben,Arbi, Mehdi El,Ferroud, Clotilde,Goya-Jorge, Elizabeth,Guenineche, Léna,Lagarde, Nathalie,Liagre, Bertrand,Martin, Frédérique,Ricco, Christophe,Riccobono, Charlotte,Veitía, Maité Sylla-Iyarreta
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Read Online
- Closing the Loop: Triazolylpyridine Coordination Drives the Self-Assembly of Metallomacrocycles with Tunable Topologies for Small-Molecule and Guanine-Quadruplex Recognition
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The 2-(1,2,3-triazol-4-yl)pyridine motif, with its facile “click” synthesis and remarkable coordinative properties, is an attractive chelate for applications in the metal-directed self-assembly of intricate three-dimensional structures. Organic ligands th
- Miron, Caitlin E.,Colden Leung, Madelaine R.,Kennedy, Emily I.,Fleischel, Olivier,Khorasani, Mona Ashraf,Wu, Nan,Mergny, Jean-Louis,Petitjean, Anne
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Read Online
- Discovery of a new class of PROTAC BRD4 degraders based on a dihydroquinazolinone derivative and lenalidomide/pomalidomide
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BRD4 has emerged as an attractive target for anticancer therapy. However, BRD4 inhibitors treatment leads to BRD4 protein accumulation, together with the reversible nature of inhibitors binding to BRD4, which may limit the efficacy of BRD4 inhibitors. To address these problems, a protein degradation strategy based on the proteolysis targeting chimera (PROTAC) technology has been developed to target BRD4 recently. Herein, we present our design, synthesis and biological evaluation of a new class of PROTAC BRD4 degraders, which were based on a potent dihydroquinazolinone-based BRD4 inhibitor compound 6 and lenalidomide/pomalidomide as ligand for E3 ligase cereblon. Gratifyingly, several compounds showed excellent inhibitory activity against BRD4, and high anti-proliferative potency against human monocyte lymphoma cell line THP-1. Especially, compound 21 (BRD4 BD1, IC50 = 41.8 nM) achieved a submicromolar IC50 value of 0.81 μM in inhibiting the growth of THP-1 cell line, and was 4 times more potent than compound 6. Moreover, the mechanism study established that 21 could effectively induce the degradation of BRD4 protein and suppression of c-Myc. All of these results suggested that 21 was an efficacious BRD4 degrader for further investigation.
- Zhang, Fangqing,Wu, Zhenwei,Chen, Pan,Zhang, Jian,Wang, Tao,Zhou, Jinpei,Zhang, Huibin
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Read Online
- HETEROBIFUNCTIONAL MOLECULES AS TEAD INHIBITORS
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The invention relates to compounds and methods of using said compounds, as well as pharmaceutical compositions containing such compounds, for treating diseases and conditions mediated by TEAD, such as cancer.
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Paragraph 0259-0260; 0323-0324
(2021/09/11)
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- SYNTHESIS OF 2-(2-AMINOETHOXY) ETHANOL
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A method for synthesizing 2-(2-aminoethoxy) ethanol, including the steps of producing 2-(2-phthalimidoethoxy) ethanol by reacting 5-tosyloxy-3-oxapentanol with potassium phthalate and converting the 2-(2-phthalimidoethoxy) ethanol to the 2-(2-aminoethoxy) ethanol by reacting the 2-(2-phthalimidoethoxy) ethanol with hydrazine monohydrate. Reacting the 2-(2-phthalimidoethoxy) ethanol with the hydrazine monohydrate may include forming a final mixture by adding the hydrazine monohydrate to a solution of 2-(2-phthalimidoethoxy) ethanol, refluxing the final mixture in a nitrogen atmosphere, extracting a second organic phase containing the 2-(2-aminoethoxy) ethanol from the final mixture using a second portion of chloroform, and purifying the 2-(2-aminoethoxy) ethanol from the second organic phase.
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Paragraph 0055-0057
(2021/02/12)
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- Fluorescent Columnar Liquid-Crystalline Polymers: Synthesis, Mesomorphic Behaviors and Tunable Emission Wavelengths?
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Fluorescent columnar liquid-crystalline polymers have attracted intensive attention due to their unique features that can be applied in many fields. However, the utilization of molecular engineering to achieve efficient fluorescence tuning has rarely been
- Hao, Xiangnan,Mu, Bin,Tian, Wei,Zhang, Zhelin,Zhao, Yu
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supporting information
p. 2009 - 2015
(2021/06/08)
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- Synthesis, biological evaluation and QSAR studies of new thieno[2,3-d]pyrimidin-4(3H)-one derivatives as antimicrobial and antifungal agents
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A series of new thieno[2,3-d]pyrimidin-4(3H)-one derivatives were synthesized and evaluated for their activity against four gram-positive and four gram-negative bacterial and eight fungal species. The majority of the compounds exhibited excellent antimicr
- Magoulas, George E.,Kalopetridou, Lefkothea,?iri?, Ana,Kritsi, Eftichia,Kouka, Paraskevi,Zoumpoulakis, Panagiotis,Chondrogianni, Niki,Sokovi?, Marina,Prousis, Kyriakos C.,Calogeropoulou, Theodora
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- Supramolecular compound nano-carrier as well as preparation method and application thereof
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The invention discloses a supramolecular compound nano-carrier as well as a preparation method and application thereof, and relates to the technical field of polymer chemistry and biological detection engineering. According to the supramolecular compound nano-carrier disclosed by the invention, a two-dimensional nanosheet supramolecular structure system generated by self-assembly is driven by an anion induction effect, and a supramolecular compound nano-carrier is of a single-layer nanosheet supramolecular structure constructed by a highly-oriented one-dimensional nanorod. A hydrophobic perylene group part is used as a skeleton part for constructing the highly-oriented one-dimensional nanorod, and the charge density of a single-layer nanosheet can be regulated and controlled. The surface of the water-soluble multivalent hydrophilic part can be loaded with DNAzyme deoxyribozyme for specific detection of heavy metal ions through electrostatic interaction, and the water-soluble multivalent supramolecular compound nano sensor is constructed. Based on a fluorescence change mechanism caused by specific cutting of heavy metal ions, The fluorescence detection of the heavy metal ions in food and biological tissues is realized, and the detection effect of the heavy metal ions is greatly enhanced.
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Paragraph 0068; 0082
(2021/08/14)
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- COMPOUNDS AND USES THEREOF
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The present disclosure features compounds and methods useful for the treatment of BAF complex-related disorders.
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Page/Page column 157
(2021/08/06)
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- TARGETED NANOPREPARATION OF MANNOSE, AND PREPARATION THEREFOR AND APPLICATION THEREOF
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The present invention relates to the field of pharmaceutical preparations, in particular, to a mannose modified targeting nano-preparations, a composition for preparing nano-preparations, a targeting element, a targeting vector, a prepared targeting drug
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Paragraph 0199; 0201; 0226
(2021/07/02)
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- Extensive structure modification on luteolin-cinnamic acid conjugates leading to BACE1 inhibitors with optimal pharmacological properties
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BACE1 inhibitory conjugates derived from two natural products, luteolin (1) and p-hydroxy-cinnamic acid (2), were subjected to systematic structure modifications, including various positions in luteolin segment for conjugation, different linkers (length, bond variation), as well as various substitutions in cinnamic acid segment (various substituents on benzene, and replacement of benzene by heteroaromatics and cycloalkane). Optimal conjugates such as 7c and 7k were chosen on the basis of a series of bioassay data for further investigation.
- Sun, De-Yang,Cheng, Chen,Moschke, Katrin,Huang, Jian,Fang, Wei-Shuo
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supporting information
(2020/01/13)
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- Lenalidomide-based small-molecular compound targeting to EGFR protein degradation, and preparation and application thereof
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The invention relates to a lenalidomide-based small-molecular compound targeting to EGFR protein degradation, and preparation and application thereof, and provides a compound targeting to ubiquitination induced EGFR protein degradation and shown as a form
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Paragraph 0050; 0051; 0052; 0053; 0054
(2020/09/09)
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- Development of small-molecule BRD4 degraders based on pyrrolopyridone derivative
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Bromodomain-containing protein 4 (BRD4) plays a crucial role in the epigenetic regulation of gene transcription and some BRD4 inhibitors have been advanced to clinical trials. Nevertheless, the clinical application of BRD4 inhibitors could be limited by drug resistance. As an alternative strategy, the emerging Proteolysis Targeting Chimeras (PROTACs) technology has the potential to overcome the drug resistance of traditional small-molecule drugs. Based on PROTACs approaches, several BRD4 degraders were developed and have been proved to degrade BRD4 protein and inhibit tumor growth. Herein, we present the design, synthesis, and biological evaluation of pyrrolopyridone derivative-based BRD4 degraders. Four synthesized compounds displayed comparative potence against BRD4 BD1 with IC50 at low nanomolar concentrations. Anti-proliferative activity of 32a against BxPC3 cell line (IC50 = 0.165 μM) was improved by about 7-fold as compared to the BRD4 inhibitor ABBV-075. Furthermore, degrader 32a potently induced the degradation of BRD4 and inhibited the expression of c-Myc in BxPC3 cell line in a time-dependent manner. The exploration of intracellular antitumor mechanism showed 32a induced cell cycle arrest and apoptosis effectively. All the results demonstrated that compound 32a could be considered as a potential BRD4 degrader for further investigation.
- Chen, Pan,Wang, Lixun,Wang, Tao,Xu, Changliang,Zhang, Huibin,Zhang, Jian,Zheng, Peiyuan,Zhou, Jinpei,Zhu, Peiyu
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- Discovery and biological evaluation of proteolysis targeting chimeras (PROTACs) as an EGFR degraders based on osimertinib and lenalidomide
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Epidermal growth factor receptor (EGFR) is one of the important and valuable drug targets. Overexpression of EGFR is associated with the development of many types of cancer. In this study, three PROTACs small molecules (16a–16c) were designed, synthesized and evaluated for their cytotoxicity against the growth in different NSCLC cell line and the degradation effect. The bioassay results indicated that 16c has a good inhibition in PC9 cells and H1975 cells, and the corresponding IC50 value was 0.413 μM and 0.657 μM, respectively. Western blotting results demonstrated that compound 16c could serve as an effective EGFRdel19-targeting degrader in PC9 cells.
- He, Kailun,Wang, Wenbing,Wang, Xiaoju,Zhang, Xingxian,Zhang, Zhuo,Zheng, Xiaoliang
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supporting information
(2020/04/21)
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- Structural basis of the inhibition of GH1 β-glucosidases by multivalent pyrrolidine iminosugars
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The synthesis of multivalent pyrrolidine iminosugars via CuAAC click reaction between different pyrrolidine-azide derivatives and tri- or hexavalent alkynyl scaffolds is reported. The new multimeric compounds, together with the monomeric reference, were evaluated as inhibitors against two homologous GH1 β-glucosidases (BglA and BglB from Paenibacillus polymyxa). The multivalent inhibitors containing an aromatic moiety in the linker between the pyrrolidine and the scaffold inhibited the octameric BglA (μM range) but did not show affinity against the monomeric BglB, despite the similarity between the active site of both enzymes. A modest multivalent effect (rp/n = 12) was detected for the hexavalent inhibitor 12. Structural analysis of the complexes between the monomeric and the trimeric iminosugar inhibitors (4 and 10) and BglA showed the insertion of the inhibitors at the active site of BglA, confirming a competitive mode of inhibition as indicated by enzyme kinetics. Additionally, structural comparison of the BglA/4 complex with the reported BglB/2F-glucose complex illustrates the key determinants responsible for the inhibitory effect and explains the reasons of the inhibition of BglA and the no inhibition of BglB. Potential inhibition of other β-glucosidases with therapeutic relevance is discussed under the light of these observations.
- Martínez-Bailén, Macarena,Jiménez-Ortega, Elena,Carmona, Ana T.,Robina, Inmaculada,Sanz-Aparicio, Julia,Talens-Perales, David,Polaina, Julio,Matassini, Camilla,Cardona, Francesca,Moreno-Vargas, Antonio J.
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supporting information
(2019/06/21)
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- Hydroquinone ether chain-linked diamine compound and synthetic method thereof
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The invention relates to a preparation method of a hydroquinone ether chain-linked diamine compound for preparing supramolecular materials. The preparation method comprises the following steps: preparing ethylene glycol p-toluenesulfonyl ester, preparing
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Paragraph 0025; 0026
(2019/03/08)
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- Hydroquinone ether chain bridged diureido pyrimidone compound and synthesis method thereof
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The invention discloses a hydroquinone ether chain bridged diureido pyrimidone compound and a synthesis method thereof, and relates to a compound and a synthesis method thereof. The hydroquinone etherchain bridged diureido pyrimidone compound is a diureid
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Paragraph 0031-0032
(2019/07/04)
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- Quadrupolar hydrogen bond assembly body and synthesis method thereof
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The invention relates to a synthesis method of a quadrupolar hydrogen bond folding assembly body material, in particular to an isoheptyle ureidopyrimidinone compound connected with a naphthyl ether chain and a synthesis method of the isoheptyle ureidopyri
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Paragraph 0026-0027
(2019/03/08)
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- Compound for targeted ubiquitin degradation of EGFR protein as well as pharmaceutical composition and application thereof
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The invention discloses a compound for targeted ubiquitin degradation of EGFR protein or a pharmaceutically acceptable salt thereof, and also discloses a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof and
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Paragraph 0043-0047
(2019/07/04)
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- Compound for targeting decomposition of EGFR proteins and preparing method and application of compound
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The invention discloses a compound for targeting decomposition of EGFR proteins with a structure shown in a formula or a pharmaceutically acceptable salt of the compound. In the formula, R representsC1-C6 alkyl groups, m is an integer of 1-7, and n is an integer of 1-6. The invention further discloses a preparing method of the compound, a drug composition comprising the compound or the pharmaceutically acceptable salt of the compound and a pharmaceutically acceptable carrier and a preparation prepared from the drug composition. The compound shows an excellent EGFR degradation effect and goodanti-tumor activity. Therefore, the invention further discloses application of the compound in preparing drugs for preventing or/and treating cancers. The compound has a huge application prospect in the field of medical treatment.
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Paragraph 0044-0047
(2019/10/01)
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- MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE
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The present disclosure relates to bifunctional compounds, which find utility as modulators of Kirsten rat sarcoma protein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation, accumulation, and/or overactivation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 00705-00706
(2019/10/29)
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- NEW HETEROCYCLIC COMPOUNDS
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The invention provides new heterocyclic compounds having the general formula (IA) wherein A, L, X, Y, m, n, R1 and R2 are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.
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Page/Page column 67; 110
(2019/06/17)
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- RADIOLABELED COMPOUNDS
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The present invention relates to radiolabeled compounds of formula (I) wherein either A, B, R1, R2, is labeled with a radionuclide selected from 3H, 11C and 18F and its use for imaging alpha synuclein and/or Abeta deposits in mammals.
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Page/Page column 84
(2019/07/13)
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- Discovery of a series of selective and cell permeable beta-secretase (BACE1) inhibitors by fragment linking with the assistance of STD-NMR
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Two β-secreatase (BACE1) inhibitors from natural products (cinnamic acid and flavone) were linked to furnish potent, cell permeable BACE1 inhibitors with noncompetitive mode of inhibition, with the assistance of saturated transfer difference (STD)-NMR technique. Some of these conjugates also exhibited selective BACE1 inhibition over other aspartyl proteases such as BACE-2 and renin, as well as poor cytotoxicity. Taken together, conjugates 4 represent a new series of BACE inhibitors warrants further investigation for their potential in Alzheimier's disease therapy.
- Fang, Wei-Shuo,Sun, De-yang,Yang, Shuang,Cheng, Chen,Moschke, Katrin,Li, Tianqi,Sun, Shanshan,Lichtenthaler, Stefan F.,Huang, Jian,Wang, Yinghong
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supporting information
(2019/09/30)
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- PYRIDAZINE DERIVATIVES AS SMARCA2/4 DEGRADERS
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The present invention provides pyridazine derivatives of formula (I), which are therapeutically useful as SMARCA2/4 degraders. These compounds are useful in the treatment and/or prevention of diseases or disorders dependent upon SMARCA2/4 in a mammal. The present invention also provides preparation of the compounds and pharmaceutical compositions comprising at least one of the pyridazine derivatives of formula (I) or a pharmaceutically acceptable salt, or a stereoisomer thereof.
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Page/Page column 105
(2019/11/12)
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- ANTIBODY-DRUG CONJUGATES
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An antibody-drug conjugate (ADC) has a structure represented by Formula (I): [in-line-formulae][D2-L2-Cn2?yG2-Ab-Sg1?G1-L1-D1]x?? Formula (I)[/in-line-formulae]or a pharmaceutically acceptable salt thereof, wherein Ab is an antibody without glycans (i.e., the protein portion of an antibody);G1 and G2 are glycan moieties, which may be the same or different;Cn1 and Cn2 are conjugation moieties, which may be the same or different;L1 and L2 are linker moieties, which may be the same or different;D1 and D2 are drug units which may be the same or different; andx and y are independently an integer from 0 to 8, provided that x+y≠0.
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Paragraph 0179; 0180
(2018/05/26)
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- EXENATIDE MODIFIER AND USE THEREOF
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Disclosed are an exenatide modifier for connecting the exenatide to a fatty chain with a carboxy in the terminus thereof by means of a hydrophilic connecting arm, and a use thereof in preparing drugs serving as a GLP-1 receptor agonist; a use in preparing drugs for preventing and/or treating diseases and/or symptoms associated with a low GLP-1 receptor activity; a use in preparing drugs for diseases and/or symptoms associated with glycometabolism; a use in preparing drugs for diabetes; a use in preparing drugs for fatty liver disease, and a use in preparing drugs for losing weight.
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Paragraph 0236
(2018/05/24)
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- Intracellular Protein-Labeling Probes for Multicolor Single-Molecule Imaging of Immune Receptor-Adaptor Molecular Dynamics
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Single-molecule imaging (SMI) has been widely utilized to investigate biomolecular dynamics and protein-protein interactions in living cells. However, multicolor SMI of intracellular proteins is challenging because of high background signals and other lim
- Sato, Ryota,Kozuka, Jun,Ueda, Masahiro,Mishima, Reiko,Kumagai, Yutaro,Yoshimura, Akimasa,Minoshima, Masafumi,Mizukami, Shin,Kikuchi, Kazuya
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supporting information
p. 17397 - 17404
(2017/12/15)
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- SILICON PHTHALOCYANINE COMPLEX, PREPARATION METHOD AND MEDICINAL APPLICATION THEREOF
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The present invention relates to a silicon phthalocyanine complex, the preparation method and the medicinal application thereof. The present invention particularly relates to a silicon phthalocyanine complex of formula (I), the preparation method thereof and a pharmaceutical composition comprising the same, as well as the use thereof as a photosensitizer, in particular the use in the treatment of cancers, wherein each substituent in formula (I) is the same as defined in the description.
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Paragraph 0090; 0091
(2017/01/26)
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- Synthesis and evaluation of novel F-18-labeled pyrimidine derivatives: Potential FAK inhibitors and PET imaging agents for cancer detection
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Based on computer-assisted drug design, a series of novel pyrimidine derivatives was successfully synthesized and characterized by 1H NMR, 13C HNMR, and MS spectra. All the new compounds were evaluated for their activity against focal adhesion kinase and showed low IC50 values in comparison with control drugs. In particular, for compound 8i, its IC50 value was 0.060 μM, suggesting its advantage as a focal adhesion kinase inhibitor. To evaluate the potentiality of these compounds as PET imaging agents in cancer detection, compounds 8a, 8c, 8h, and 8i were successively labeled with 18F. The four 18F-labeled pyrimidine derivatives showed appropriate log P values and high stability in physiological saline and mouse plasma. Noticeably, compound [18F]-8a with a 4-methoxyl group at the benzene ring exhibited good in vivo biodistribution data in mice bearing the S180 tumor, which promoted a further microPET imaging study of compound [18F]-8a. The microPET image of [18F-8a] administered into the S180 tumor-bearing mice acquired at 60 min post-injection illustrated that the uptake in S180 tumor was obvious. These results suggested that compound [18F]-8a might be a new probe for PET tumor imaging.
- Wang, Dawei,Fang, Yu,Wang, Hang,Xu, Xingyu,Liu, Jianping,Zhang, Huabei
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p. 22388 - 22399
(2017/07/10)
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- Carbazole and Carboline Compounds for Use in the Diagnosis, Treatment, Alleviation or Prevention of Disorders Associated with Amyloid or Amyloid-Like Proteins
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The present invention relates to novel compounds that can be employed in the diagnosis, treatment, alleviation or prevention of a group of disorders and abnormalities associated with amyloid proteins and amyloid-like proteins, such as Alzheimer's disease. Precursors for the preparation of the compounds according to the present invention are also provided.
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Paragraph 1041; 1042; 1043; 1044
(2017/01/23)
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- SULFINYLPHENYL OR SULFONIMIDOYLPHENYL BENZAZEPINES
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This invention relates to novel sulfinylphenyl or sulfonimidoylphenyl benzazepine compounds of the formula (I) wherein X and R1 to R6 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are TLR agonists and may therefore be useful as medicaments for the treatment of diseases such as cancer, autoimmune diseases, inflammation, sepsis, allergy, asthma, graft rejection, graft-versus-host disease, immunodeficiencies, and infectious diseases.
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Page/Page column 33; 34
(2017/04/11)
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- Candidate PET Radioligand Development for Neurofibrillary Tangles: Two Distinct Radioligand Binding Sites Identified in Postmortem Alzheimer's Disease Brain
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[18F]THK-523 and [18F]807 are promising radioligands for imaging neurofibrillary tangles (NFTs) with positron emission tomography (PET) in neurodegenerative diseases, such as Alzheimer's disease (AD) and traumatic brain injury. Although [18F]THK-523 and [18F]T807 are considered high-affinity selective radioligands for NFTs, uncertainty has existed as to whether PET radioligands for imaging NFTs bind to the same molecular site because in vitro assays for ligands binding to NFTs have been lacking. We labeled THK-523 and T807 with tritium to serve as reference radioligands for in vitro binding assays with AD brain homogenates for newly synthesized ligands. With these radioligands, we identified two distinct binding sites for small molecules, one site with high affinity for THK-523 and the other with high affinity for T807. Moreover, binding assays with [3H]PIB confirmed that the two newly identified binding sites are also distinct from the thioflavin-T binding site where all current clinically useful PET radioligands for imaging β-amyloid plaque bind with high affinity. The two newly identified binding sites are considered to reside on NFTs rather than on β-amyloid plaques. Furthermore, we applied all three binding assays to a set of newly prepared compounds, based on chain modifications to THK-523. Some compounds with high affinity and selectivity for the THK-523 binding site emerged from this set, including one with amenability to labeling with fluorine-18, namely, ligand 10b.
- Cai, Lisheng,Qu, Baoxi,Hurtle, Bryan T.,Dadiboyena, Sureshbabu,Diaz-Arrastia, Ramon,Pike, Victor W.
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p. 897 - 911
(2016/08/02)
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- CARBAZOLE AND CARBOLINE COMPOUNDS FOR USE IN THE DIAGNOSIS, TREATMENT, ALLEVIATION OR PREVENTION OF DISORDERS ASSOCIATED WITH AMYLOID OR AMYOLID-LIKE PROTEINS
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The present invention relates to novel compounds that can be employed in the diagnosis, treatment, alleviation or prevention of a group of disorders and abnormalities associated with amyloid proteins and amyloid-like proteins, such as Alzheimer's disease. Precursors for the preparation of the compounds according to the present invention are also provided.
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Page/Page column 239; 240
(2015/08/06)
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- Synthesis of Novel Di Benzo spiro bis-crown-ether
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This paper focuses on the synthesis of a wide variety of di benzo spiro bis-crown compounds, in good yields using di-phenols, mono tosylates of oligoethylene glycols and caesium carbonate in acetonitrile.
- Lari, Jalil,Moradgholi, Fatemeh,Vahedi, Hooshang,Massoudi, Abdolhossein
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p. 668 - 673
(2015/11/09)
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- BCR-ABL TYROSINE-KINASE LIGANDS CAPABLE OF DIMERIZING IN AN AQUEOUS SOLUTION, AND METHODS OF USING SAME
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Described herein are monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. invivo) to form a multimer (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding sites on a Bcr-Abl tyrosine kinase.
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Paragraph 00442; 00459; 00460
(2015/07/23)
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- PEPTIDE CONTAINING CONJUGATES FOR DUAL MOLECULAR DELIVERY OF OLIGONUCLEOTIDES
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Disclosed herein is a peptide containing conjugate comprising (P)c-(L)d-(G)e, wherein P is a peptide and each occurance of P is independently selected from Table 2; L is an optional linker and each occurance of L, if prese
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Page/Page column 84; 85
(2015/05/26)
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- DUAL MOLECULAR DELIVERY OF OLIGONUCLEOTIDES AND PEPTIDE CONTAINING CONJUGATES
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Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)a-(G)b; wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a li
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Page/Page column 85; 86
(2015/05/26)
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- An electrochemically switched smart surface for peptide immobilization and conformation control
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We report an electrochemically switched smart surface for controlled peptide immobilization and conformation control. This dynamic surface is based on self-assembled monolayers (SAMs) containing surface-bound trimethoxybenzene moieties, which can undergo
- Li, Jun,Sun, Chun-Lin,Shen, Rong,Cao, Xiao-Yan,Zhou, Bo,Bai, De-Cheng,Zhang, Hao-Li
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supporting information
p. 11050 - 11056
(2014/08/18)
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- Synthesis, cytotoxicity, DNA binding and topoisomerase II inhibition of cassiarin A derivatives
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Four series of cassiarin A derivatives with alkanoyl (3a-3d), aroyl (4a-4d), hydroxy/amino-substituted ethylene glycol (5a-5c) and selenium-containing (6a) side chains were synthesized. Their antitumor activities were evaluated against BT474, CHAGO, HepG2
- Luesakul, Urarika,Palaga, Tanapat,Krusong, Kuakarun,Ngamrojanavanich, Nattaya,Vilaivan, Tirayut,Puthong, Songchan,Muangsin, Nongnuj
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supporting information
p. 2845 - 2850
(2014/06/10)
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- Synthesis of galactoclusters by metal-free thiol "click chemistry" and their binding affinities for pseudomonas aeruginosa lectin leca
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Mannose-centered galactoclusters specific for lectin I of Pseudomonas aeruginosa (LecA) were synthesised by a combination of phosphoramidite chemistry and metal-free thiol click chemistry (i.e., thiol addition to acrylamide or nucleophilic displacement of
- Ligeour, Caroline,Dupin, Lucie,Marra, Alberto,Vergoten, Gérard,Meyer, Albert,Dondoni, Alessandro,Souteyrand, Eliane,Vasseur, Jean-Jacques,Chevolot, Yann,Morvan, Fran?ois
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supporting information
p. 7621 - 7630
(2015/04/22)
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- DUAL TARGETING COMPOUNDS FOR THE TREATMENT OF ALZHEIMER'S DISEASE
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Compounds of formula (I) wherein the groups are as defined in the description, are used as medicaments, in particular for the treatment of a disease selected from the group consisting of: cognitive impairment, memory dysfunction, neurodegenerative disorde
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Page/Page column 43; 44
(2013/11/18)
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- Synthesis and in vitro photodynamic activity of Oligomeric ethylene glycol-quinoline substituted zinc(II) phthalocyanine derivatives
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A new series of zinc(II) phthalocyanine derivatives have been synthesized and characterized. These macrocycles exhibited a sharp absorption band in the red visible region in DMF, which indicated that they were dissolved well and almost did not aggregate i
- Jia, Xiao,Yang, Feng-Feng,Li, Jun,Liu, Jian-Yong,Xue, Jin-Ping
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p. 5797 - 5805
(2013/08/23)
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- Synthesis of novel, fluorescently tagged analogs of glycosylphosphatidylinositol (GPI) anchors
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Glycosylphosphatidylinositol (GPI) anchors are a group of complex glycolipids that attach extracellular proteins and glycoproteins to the eukaryotic cell outer membrane. To better understand GPI anchorage, it is necessary to have access to homogeneous, structurally defined, and functionalized GPIs and GPI analogs. In this regard, chemical synthesis is necessary, as GPI anchors are rather scarce and heterogeneous in natural sources. Three GPI analogs with phosphoglycerolipids linked to the pseudodisaccharide core and their fluorescein conjugates were prepared in this work as a small tool set useful for probing how the lipid composition and carbohydrate anomeric configuration may affect the properties of GPI anchors.
- Johnson, Charles L.,Guo, Zhongwu
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p. 301 - 323
(2013/10/08)
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- Design and synthesis of protoporphyrin IX/vitamin B12 molecular hybrids via CuAAC reaction
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The design and synthesis of new molecular hybrids composed of protoporphyrin IX (PPIX) and vitamin B12 via copper catalyzed alkyne azide cycloaddition reaction is described. New, clickable aminoazide and aminoalkyne linkers were prepared and subsequently attached to PPIX (via vinyl group) and to vitamin B12 giving desired building blocks. Preliminary results showed that respective water soluble hybrids were formed under CuAAC reaction. Gratifyingly, Cu incorporation into the PPIX core was avoided, which was important for further biological studies. Copyright
- Loska, Rafa?,Janiga, Anita,Gryko, Dorota
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p. 104 - 117
(2013/04/23)
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- NOVEL TETRAGALNAC CONTAINING CONJUGATES AND METHODS FOR DELIVERY OF OLIGONUCLEOTIDES
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Disclosed herein is a modular composition comprising 1) an oligonucleotide; 2) one or more tetraGalNAc ligands of Formula (I), which may be the same or different; optionally, 3) one or more linkers, which may be the same or different; and optionally, 4) o
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Page/Page column 29
(2013/11/19)
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- NOVEL TETRAGALNAC AND PEPTIDE CONTAINING CONJUGATES AND METHODS FOR DELIVERY OF OLIGONUCLEOTIDES
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Disclosed herein is a modular composition comprising 1) an oligonucleotide; 2) one or more tetraGalNAc ligands of Formula (I), which may be the same or different; optionally, 3) one or more linkers, which may be the same or different; 4) one or more peptides independently selected from Table 3, which may be the same or different; and optionally, 5) one or more targeting ligands, solubilizing agents, pharmacokinetics enhancing agents, lipids, and/or masking agents.
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Page/Page column 76
(2013/11/19)
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- SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS
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The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of gene expression and/or activity, and/or modulate a gene expression pathway.
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Page/Page column 112
(2013/11/19)
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