- Polyrotaxane-Mediated Self-Assembly of Gold Nanospheres into Fully Reversible Supercrystals
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The use of a thiol-functionalized nonionic surfactant to stabilize spherical gold nanoparticles in water induces the spontaneous formation of polyrotaxanes at the nanoparticle surface in the presence of the macrocycle α-cyclodextrin. Whereas using an exce
- Coelho, Joao Paulo,González-Rubio, Guillermo,Delices, Annette,Barcina, José Osío,Salgado, Cástor,ávila, David,Pe?a-Rodríguez, Ovidio,Tardajos, Gloria,Guerrero-Martínez, Andrés
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Read Online
- From the Promiscuous Asenapine to Potent Fluorescent Ligands Acting at a Series of Aminergic G-Protein-Coupled Receptors
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Monoamine neurotransmitters such as serotonin, dopamine, histamine, and noradrenaline have important and varied physiological functions and similar chemical structures. Representing important pharmaceutical drug targets, the corresponding G-protein-couple
- Hounsou, Candide,Baehr, Corinne,Gasparik, Vincent,Alili, Doria,Belhocine, Abderazak,Rodriguez, Thiéric,Dupuis, Elodie,Roux, Thomas,Mann, André,Heissler, Denis,Pin, Jean-Philippe,Durroux, Thierry,Bonnet, Dominique,Hibert, Marcel
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Read Online
- Control over the macrocyclisation pathway and product topology in a copper-templated catenane synthesis
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We report here that the product topology in a copper-templated catenane synthesis can be controlled by favouring a particular macrocyclisation pathway, offering an additional strategy for improving the efficiency of catenane formation. A linear [4]catenan
- Yee, Chi-Chung,Ng, Antony Wing Hung,Au-Yeung, Ho Yu
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Read Online
- Thiol-Functionalized IGEPAL Surfactants as Novel Fluorescent Ligands for the Silica Coating of Gold Nanoparticles
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A synthesized thiol-functionalized non-ionic surfactant based on the IGEPAL (polyoxyethylene(5) nonyl phenyl ether) structure, has been used to replace citrate ions from the surface of gold nanoparticles with 13.5 nm diameters. Upon IGEPAL-type stabilizat
- Gaviln-Rubio, Helena,Coelho, Joo Paulo,Gonzlez-Rubio, Guillermo,Tardajos, Gloria,Barcina, Jos Oso,Salgado, Castor,Guerrero-Martnez, Andrs
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Read Online
- Solid phase synthesis of functionalised SAM-forming alkanethiol- oligoethyleneglycols
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We present an efficient solid phase synthesis methodology that provides easy access to a range of functionalised long-chain alkanethiol- oligoethyleneglycols that form well-defined self-assembled monolayers on gold and are compatible with pre- or post-ass
- Murray, James,Nowak, Dominika,Pukenas, Laurynas,Azhar, Rizuan,Guillorit, Mathieu,Waelti, Christoph,Critchley, Kevin,Johnson, Steven,Bon, Robin S.
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Read Online
- BIFUNCTIONAL COMPOUNDS FOR DEGRADING BTK VIA UBIQUITIN PROTEOSOME PATHWAY
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The present invention relates to compounds of formula (I) useful for degrading BTK via a ubiquitin proteolytic pathway. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.
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Paragraph 0893; 0895; 0901
(2021/05/15)
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- TARGETED BIFUNCTIONAL DEGRADERS
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The present invention provides, in one aspect, bifunctional compounds that can be used to promote or enhance degradation of certain circulating proteins. In another aspect, the present invention provides bifunctional compounds that can be used to promote or enhance degradation of certain autoantibodies. In certain embodiments, treatment or management of a disease and/or disorder requires degradation, removal, or reduction in concentration of the circulating protein or the autoantibody in the subject. Thus, in certain embodiments, administration of a compound of the invention to the subject removes or reduces the circulation concentration of the circulating protein or the autoantibody, thus treating, ameliorating, or preventing the disease and/or disorder. In certain embodiments, the circulating protein is TNF.
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Page/Page column 189
(2021/04/17)
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- BIFUNCTIONAL MOLECULES CONTAINING AN E3 UBIQUITINE LIGASE BINDING MOIETY LINKED TO A BCL6 TARGETING MOIETY
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Bifunctional compounds, which find utility as modulators of B-cell lymphoma 6 protein (BCL6; target protein), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand that 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 bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 00561; 00562
(2021/04/23)
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- 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 0275-0276; 0307-0308; 0456-0457; 0474-0475
(2021/09/11)
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- POLYCYCLIC COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF RAPIDLY ACCELERATED FIBROSARCOMA POLYPEPTIDES
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The present disclosure relates to bifunctional compounds, ULM— L—PTM, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (RAF, such as c-RAF, A- RAF and/or B-RAF; the 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 RAF, 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 or accumulation of the target protein, or the constitutive activation of the target protein, are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 2144; 2145
(2020/03/29)
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- 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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supporting information
(2020/01/31)
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- THERAPEUTIC METHODS
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The invention provides methods and compositions for delivering a nucleic acid to a cell or the cytosol of the target cell. The method includes contacting the cell with, 1) a membrane-destabilizing polymer; and 2) a nucleic acid conjugate. The nucleic acid conjugate includes a targeting ligand bound to an optional linker and a nucleic acid.
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Page/Page column 149; 151
(2020/05/28)
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- MERTK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 00674; 00676
(2020/01/31)
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- IRAK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 2097; 2098
(2019/07/10)
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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 001248-001249
(2019/10/29)
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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 0044-0045; 0055-0057
(2019/10/01)
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- METHODS FOR TREATING HEPATITIS B INFECTIONS
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Certain embodiments of the invention provide a method for identifying a patient that has a higher likelihood of responding to an HBV antigen inhibitor, such a method comprising detecting a hepatitis B virus (HBV) infected patient's genotype at one or more of the IL28B/A associated SNPs described herein, wherein the relevant genotype(s) described herein are indicative of a patient that has a higher likelihood of responding to an HBV antigen inhibitor as compared to an HBV infected patient having different genotypes at these locations.
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Page/Page column 217-219
(2019/04/09)
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- Molecular Swings as Highly Active Ion Transporters
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Ions are transported across membrane mostly via carrier or channel mechanisms. Herein, a unique class of molecular-machine-inspired membrane transporters, termed molecular swings is reported that utilize a previously unexplored swing mechanism for promoting ion transport in a highly efficient manner. In particular, the molecular swing, which carries a 15-crown-5 unit as the ion-binding and transporting unit, exhibits extremely high ion-transport activities with EC50 values of 46 nm (a channel:lipid molar ratio of 1:4800 or 0.021 mol % relative to lipid) and 110 nm for K+ and Na+ ions, respectively. Remarkably, such ion transport activities remain high in a cholesterol-rich environment, with EC50 values of 130 (0.045 mol % relative to lipid/cholesterol) and 326 nm for K+ and Na+ ions, respectively.
- Ren, Changliang,Chen, Feng,Ye, Ruijuan,Ong, Yong Siang,Lu, Hongfang,Lee, Su Seong,Ying, Jackie Y.,Zeng, Huaqiang
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supporting information
p. 8034 - 8038
(2019/05/16)
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- BIHETEROCYCLIC COMPOUND
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The present invention provides a compound of formula (1) and a pharmaceutical composition comprising the compound useful as a nerve regeneration promoter wherein R1-L- is R1—OC(O)—, or the like, R1 is hydrogen atom, optionally-substituted C1-6 alkyl group, optionally-substituted 3- to 8-membered cycloalkyl group, or the like, R2 is hydrogen atom or the like, Ring A is formula (2) or formula (3) wherein R3 is hydrogen atom, optionally-substituted C1-6 alkyl group, or the like, the part of X, Y, and Z is X═Y—Z, X—Y═Z, or X—Y—Z, X is nitrogen atom, NR4 (R4 is hydrogen atom, optionally-substituted C1-6 alkyl group, or the like), or the like, Y is carbon atom or the like, and Z is carbon atom, nitrogen atom or the like.
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Paragraph 1169-1171
(2019/02/01)
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- Ion Conducting ROMP Monomers Based on (Oxa)norbornenes with Pendant Imidazolium Salts Connected via Oligo(oxyethylene) Units and with Oligo(ethyleneoxy) Terminal Moieties
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A matrix of 22 two-armed norbornene-based imidazolium TFSI monomers (8) was synthesized to determine the optimal structure in terms of single ion conductivity. For the chain tethering the imidazolium ring to the norbornene ring three or four oxyethylene units are optimal. A terminal group of two ethyleneoxy units was optimal. NMR studies indicated that both the tether oxyethylene units and the terminal ethyleneoxy units interact with the imidazolium cation via hydrogen bonding. 8r (X = 4, Y = 2) exhibited a conductivity of 9.57 × 10-5 S/cm at 25 °C and a Tg of -46 °C. Low Tg values do not correlate with higher conductivity as a result of the H-bonding interactions. Stability toward autopolymerization and reasonable conductivities provide an acceptable platform for ion conducting ROMP polymers. Four one-armed norbornene-based imidazolium TFSI monomers (15) were prepared with tetra(ethyleneoxy) linkers/spacers and variable terminal groups. All of these exhibited low Tgs (10-4 S/cm, the highest being 4.39 × 10-4 S/cm for 15c (Tg = -69 °C), the analogue of 8r, providing hope for outstanding polymers. Three oxanorbornene-based two-armed imidazolium TFSI monomers (18) were prepared with varied linkers and terminal groups. 18b possesses a room temperature conductivity of 1.2 × 10-4 S/cm, again augering well for polymers derived therefrom by ROMP.
- Price, Terry L.,Choi, U Hyeok,Schoonover, Daniel V.,Arunachalam, Murugan,Xie, Renxuan,Lyle, Steven,Colby, Ralph H.,Gibson, Harry W.
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p. 1371 - 1388
(2019/02/19)
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- BIFUNCTIONAL SMALL MOLECULES TO TARGET THE SELECTIVE DEGRADATION OF CIRCULATING PROTEINS
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The present invention is directed to bifunctional small molecules which contain a circulating protein binding moiety (CPBM) linked through a linker group to a cellular receptor binding moiety (CRBM) which is a membrane receptor of degrading cell such as a hepatocyte or other degrading cell. In embodiments, the (CRBM) is a moiety which binds to asialoglycoprotein receptor (an asialoglycoprotein receptor binding moiety, or ASGPRBM) of a hepatocyte. In additional embodiments, the (CRBM) is a moiety which binds to a receptor of other cells which can degrade proteins, such as a LRP1, LDLR, FcyRI, FcRN, Transferrin or Macrophage Scavenger receptor. Pharmaceutical compositions based upon these bifunctional small molecules represent an additional aspect of the present invention. These compounds and/or compositions may be used to treat disease states and conditions by removing circulating proteins through degradation in the hepatocytes or macrophages of a patient or subject in need of therapy. Methods of treating disease states and/or conditions in which circulating proteins are associated with the disease state and/or condition are also described herein.
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Page/Page column 72
(2019/11/04)
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- TARGETED COMPOSITIONS
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The invention provides certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic double stranded siRNA to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).
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Page/Page column 137; 139
(2018/11/10)
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- Highly Ordered Self-Assembly of Native Proteins into 1D, 2D, and 3D Structures Modulated by the Tether Length of Assembly-Inducing Ligands
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In nature, proteins self-assemble into various structures with different dimensions. To construct these nanostructures in laboratories, normally proteins with different symmetries are selected. However, most of these approaches are engineering-intensive and highly dependent on the accuracy of the protein design. Herein, we report that a simple native protein LecA assembles into one-dimensional nanoribbons and nanowires, two-dimensional nanosheets, and three-dimensional layered structures controlled mainly by small-molecule assembly-inducing ligands RnG (n=1, 2, 3, 4, 5) with varying numbers of ethylene oxide repeating units. To understand the formation mechanism of the different morphologies controlled by the small-molecule structure, molecular simulations were performed from microscopic and mesoscopic view, which presented a clear relationship between the molecular structure of the ligands and the assembled patterns. These results introduce an easy strategy to control the assembly structure and dimension, which could shed light on controlled protein assembly.
- Yang, Guang,Ding, Hong-Ming,Kochovski, Zdravko,Hu, Rongting,Lu, Yan,Ma, Yu-Qiang,Chen, Guosong,Jiang, Ming
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supporting information
p. 10691 - 10695
(2017/08/30)
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- ALANINE-BASED MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE
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The description relates to inhibitors of Apoptosis Proteins (TAPs) binding compounds, including Afunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the IAP E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.
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Paragraph 00430
(2017/02/09)
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- TARGETED NUCLEIC ACID CONJUGATE COMPOSITIONS
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The invention provides conjugates that comprise a targeting moiety, a nucleic acid, and optional linking groups as well as synthetic intermediates and synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic nucleic acids to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).
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Page/Page column 110; 112
(2017/11/10)
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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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- TUNABLE PHENYLACETYLENE HOSTS
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A compound, or a salt thereof, having the formula wherein Y is n is 1 or 2; each R is independently H, alkyl, substituted alkyl, a polyether moiety, carboxyl, substituted carboxyl, carbamate, substituted carbonate, carbonyloxy, alkoxy, substituted alkoxy,
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Paragraph 0275
(2014/02/16)
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- 1,8-Dioxyanthracene-Derived Crown Ethers: Synthesis, Complexation with Paraquat and Assembly of a Tetracationic Cyclophane-Crown Ether Based [2]Catenane
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1,8-Dioxyanthracene-based bisarylene crown ethers, composed of ethylene glycol chains and aromatic moieties, have been synthesized. Complexation studies revealed that these crown ethers could form 1:1 complexes with methyl viologen dication (N,N′-dimethyl
- Tang, Bo,Yang, Hong-Mei,Hu, Wen-Jing,Ma, Ming-Liang,Liu, Yahu A.,Li, Jiu-Sheng,Jiang, Biao,Wen, Ke
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p. 6925 - 6934
(2016/02/19)
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- Structural fine-tuning of (-donor-spacer-acceptor-spacer-)n type foldamers. Effect of spacer segment length, temperature, and metal-ion complexation on the folding process
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The synthesis of a series of polymers (PDA-nOE) containing an alternating arrangement of electron rich (donor) and electron deficient (acceptor) aromatic units, which are linked by flexible oligo(oxyethylene) (nOE) spacers, is reported. The length of the
- Ghosh, Suhrit,Ramakrishnan
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p. 676 - 686
(2007/10/03)
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- Silver(I) oxide mediated highly selective monotosylation of symmetrical diols. Application to the synthesis of polysubstituted cyclic ethers
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(Matrix Presented) The reaction of symmetrical diols and oligo(ethylene glycol)s with a stoichiometric amount of p-toluenesulfonyl chloride in the presence of silver(I) oxide and a catalytic amount of potassium iodide led selectively to the monotosylate derivatives in high yields. Polysubstituted cyclic ethers were obtained readily upon treatment of the corresponding diols with an excess of silver oxide. The high selectivity was explained on the basis of the difference in acidity between the two hydroxy groups, which undergo an intramolecular hydrogen bonding.
- Bouzide, Abderrahim,Sauve, Gilles
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p. 2329 - 2332
(2007/10/03)
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- Phenothiazine - Bipyridinium cyclophanes
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The syntheses of oligooxa[8.8]-, -[11.11]-, -[14,14]-, -[17.17]and -[20.20]cyclophanes with phenothiazine as donor and bipyridinium dication as acceptor are described, together with preparations of the corresponding oligomethylene-[3.3]and -[4.4]cyclophanes. While the large [8.8]-, [11.11]- and [14.14]cyclophanes in particular show well-defined charge-transfer (CT) absorption maxima, the smallest [3.3]cyclophane does not exhibit any CT effect. For the large cyclophanes, a preferred conformation with crossed donor and acceptor units is proposed. The fluorescence quenching and electrochemical behaviour of all phenothiazine - bipyridinium cyclophanes is discussed.
- Bauer, Helmut,Stier, Falk,Petry, Christoph,Knorr, Andreas,Stadler, Christian,Staab, Heinz A.
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p. 3255 - 3278
(2007/10/03)
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- Dipyrido[3,2-a:2',3'-c]phenazine-tethered oligo-DNA: Synthesis and thermal stability of their DNA·DNA and DNA·RNA duplexes and DNA·DNA·DNA triplexes
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Dipyrido[3,2-a:2',3'-c]phenazine (dppz) derivatives were conjugated to 9-mer and 18-mer DNA (ODN) at a site without nucleobase, either at the 5'- or 3'-end or at a internucleotide position, via linkers of 7, 12, or 18 atoms lengths. These dppz-linked ODNs
- Ossipov, Dimitri,Zamaratski, Edouard,Chattopadhyava, Jyoti
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p. 2186 - 2200
(2007/10/03)
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- Podand Ionophores Capable of Forming Cation-Binding Cavities through Intramolecular Interactions between the Terminal Groups
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A series of podand hosts having suitable cavities for metal cations in virtue of intramolecular interactions between the terminal groups were designed and synthesized.The conformational informations of hosts were obtained by NMR studies including homonuclear NOE difference experiments.Intramolecular interactions between the terminal groups of podand hosts markedly increase binding affinities and selectivities to metal cations.
- Jeong, Kyu-Sung,Cho, Young Lag,Pyun, Seung Yup
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p. 2827 - 2830
(2007/10/02)
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