- Macrocyclic DNA-mismatch-binding ligands: Structural determinants of selectivity
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A collection of 15 homodi- meric and 5 heterodimeric macrocyclic bisintercalators was prepared by one- or two-step condensation of aromatic dialdehydes with aliphatic diamines; notably, the heterodimeric scaffolds were synthesized for the first time. The binding of these macrocycles to DNA duplexes containing a mispaired thy- mine residue (TX), as well as to the fully paired control (TA), was investi- gated by thermal denaturation and flu- orescent-intercalator-displacement experiments. The bisnaphthalene derivatives, in particular, the 2, 7-disubstituted ones, have the highest selectivity for the TX mismatches, as these macrocy- cles show no apparent binding to the fully paired DNA. By contrast, other macrocyclic ligands, as well as seven conventional DNA binders, show lesser or no selectivity for the mismatch sites. The study demonstrates that the topology of the ligands plays a crucial role in determining the mismatch-binding affinity and selectivity of the macrocy- clic bisintercalators. 2010 Wiley-VCH Verlag GmbH & Co. KGaA.
- Granzhan, Anton,Largy, Eric,Saettel, Nicolas,Teulade-Fichou, Marie-Paule
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Read Online
- Development of novel cyclic peptides as pro-apoptotic agents
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Our recent finding that paclitaxel behaves as a peptidomimetic of the endogenous protein Nur77 inspired the design of two peptides (PEP1 and PEP2) reproducing the effects of paclitaxel on Bcl-2 and tubulin, proving the peptidomimetic nature of paclitaxel.
- Brindisi, Margherita,Maramai, Samuele,Brogi, Simone,Fanigliulo, Emanuela,Butini, Stefania,Guarino, Egeria,Casagni, Alice,Lamponi, Stefania,Bonechi, Claudia,Nathwani, Seema M.,Finetti, Federica,Ragonese, Francesco,Arcidiacono, Paola,Campiglia, Pietro,Valenti, Salvatore,Novellino, Ettore,Spaccapelo, Roberta,Morbidelli, Lucia,Zisterer, Daniela M.,Williams, Clive D.,Donati, Alessandro,Baldari, Cosima,Campiani, Giuseppe,Ulivieri, Cristina,Gemma, Sandra
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Read Online
- Specific fluorescence labeling of target proteins by using a ligand-4-azidophthalimide conjugate
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We herein propose a simple affinity-labeling method using a ligand-4-azidophthalimide (AzPI) conjugate. As a proof of concept, we show that two different ligand-AzPI conjugates enabled highly specific fluorescence labeling of their individual target proteins even in crude cell lysates. This method was also applied to label endogenous target proteins inside living cells.
- Chiba, Kosuke,Asanuma, Miwako,Ishikawa, Minoru,Hashimoto, Yuichi,Dodo, Kosuke,Sodeoka, Mikiko,Yamaguchi, Takao
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Read Online
- Facile synthesis and evaluation of C-functionalized benzyl-1-oxa-4,7,10- triazacyclododecane-N,N′,N″-triacetic acid as chelating agent for 111In-labeled polypeptides
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A 12-membered polyazamacrocycle, 1-oxa-4,7,10-triazacyclododecane-N, N′,N″-triacetic acid (ODTA), has been reported to provide an indium chelate of net neutral charge with thermodynamic stability higher than 1,4,7,10-tetraazacyclododecane-N,N′,N″,N?-tetra
- Suzuki, Hiroyuki,Kanai, Ayaka,Uehara, Tomoya,Guerra Gomez, Francisco L.,Hanaoka, Hirofumi,Arano, Yasushi
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Read Online
- Synthesis and evaluation of a pseudocyclic tristhiourea-based anion host
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A novel methodology for the evaluation of receptor arrangement in structurally flexible anion chemosensors was developed and applied to map the binding site of a new pseudocyclic tristhiourea chemosensor (6). The syntheses of 6 and related macrocyclic chemosensor 10 (a model of the folded monomeric structure of 6) are reported. Both chemosensors were evaluated by titration with a variety of structurally different anions in CH3Cl and DMSO, showing a common preference for F-, CH3CO2 -, and H2PO4-. However, within this group of anions, the binding patterns of the chemosensors differed, indicating dissimilarity in the arrangement of the binding sites of 6 and 10.
- Dahan, Adi,Ashkenazi, Tali,Kuznetsov, Vladimir,Makievski, Svetlana,Drug, Eyal,Fadeev, Ludmila,Bramson, Maayan,Schokoroy, Sari,Rozenshine-Kemelmakher, Emily,Gozin, Michael
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Read Online
- LIGAND DRUG CONJUGATES AND MODIFIED BET INHIBITORS
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A ligand drug conjugate comprising a) a targeting ligand; b) a cleavable bridge; and a bromodomain and extraterminal (BET) inhibitor is provided. The targeting ligand may comprise a cancer targeting ligand. The BET inhibitor may comprise I-BET762, (+)-JQ1, MS417, OXT015, (2), RVX-208, (3), OXFBD02, OXFBD03, I-BET151, (4), PFI-1, I-BET726, MS436, XD14 or a modified BET inhibitor. Modified BET inhibitors are also provided, including RT48 ((S) -2- (6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-benzo[f] [1,2,4] triazolo [4,3-a] [1,4] diazepin-4-yl)-1-(4-(dimethylamino) piperidin-1-yl) ethan-1-one) and RT53 ((S) -2- (6- (4-chlorophenyl) -8-methoxy-1-methyl-4H-benzo[f] [1,2,4] triazolo [4,3-a] [1,4] diazepin-4-yl) -N-(4- (4- (dimethylamino) piperidin-1-yl) phenyl) acetamide). A pro-drug of a BET inhibitor is also provided. A method of preparing a ligand drug conjugate according to the invention is also provided. The method comprises i) functionalising a BET inhibitor with a tertiary amine to form a modified BET inhibitor according to the invention; ii) bonding the modified BET inhibitor formed in step i) to a cleavable bridge; and iii) bonding the cleavable bridge bound to the modified BET inhibitor formed in step ii) to a targeting ligand. A ligand drug conjugate according to the invention for use as a medicament is also provided.
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(2021/07/17)
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- Design, Synthesis, and Evaluation of VHL-Based EZH2 Degraders to Enhance Therapeutic Activity against Lymphoma
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Traditional EZH2 inhibitors are developed to suppress the enzymatic methylation activity, and they may have therapeutic limitations due to the nonenzymatic functions of EZH2 in cancer development. Here, we report proteolysis-target chimera (PROTAC)-based EZH2 degraders to target the whole EZH2 in lymphoma. Two series of EZH2 degraders were designed and synthesized to hijack E3 ligase systems containing either von Hippel-Lindau (VHL) or cereblon (CRBN), and some VHL-based compounds were able to mediate EZH2 degradation. Two best degraders, YM181 and YM281, induced robust cell viability inhibition in diffuse large B-cell lymphoma (DLBCL) and other subtypes of lymphomas, outperforming a clinically used EZH2 inhibitor EPZ6438 (tazemetostat) that was only effective against DLBCL. The EZH2 degraders displayed promising antitumor activities in lymphoma xenografts and patient-derived primary lymphoma cells. Our study demonstrates that EZH2 degraders have better therapeutic activity than EZH2 inhibitors, which may provide a potential anticancer strategy to treat lymphoma.
- Tu, Yalin,Sun, Yameng,Qiao, Shuang,Luo, Yao,Liu, Panpan,Jiang, Zhong-Xing,Hu, Yumin,Wang, Zifeng,Huang, Peng,Wen, Shijun
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p. 10167 - 10184
(2021/07/26)
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- Design, synthesis and biological evaluation of tyrosinase-targeting PROTACs
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The human tyrosinase is the most prominent therapeutic target for pigmentary skin disorders. However, the overwhelming majority efforts have been devoted to search mushroom tyrosinase inhibitors, which show poor inhibitory activity on human tyrosinase and certain side effects that cause skin damage in practical application. Herein, a series of degraders that directly targeted human tyrosinase was firstly designed and synthesized based on newly developed PROTAC technology. The best PROTAC TD9 induced human tyrosinase degradation obviously in dose and time-dependent manner, and its mechanism of inducing tyrosinase degradation has also been clearly demonstrated. Besides, encouraging results that low-toxicity PROTAC TD9 was applied to reduce zebrafish melanin synthesis have been obtained, highlighting the potential to treatment of tyrosinase-related disorders. Moreover, this work has innovatively expanded the application scope of PROTAC technology and laid a solid foundation for further development of novel drugs treating pigmentary skin disorders.
- Cui, Xin,Deng, Yun,Fu, Dingqiang,Li, Guangxun,Qin, Fengming,Tang, Zhuo,Xu, Yan,Yao, Shaohua,Yuan, Yi
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supporting information
(2021/10/12)
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- A MedChem toolbox for cereblon-directed PROTACs
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A modular chemistry toolbox was developed for cereblon-directed PROTACs. A variety of linkers was attached to a CRBN ligand via the 4-amino position of pomalidomide. We used linkers of different constitution to modulate physicochemical properties. We equipped one terminus of the linker with a set of functional groups, e.g. protected amines, protected carboxylic acids, alkynes, chloroalkanes, and protected alcohols, all of which are considered to be attractive for PROTAC design. We also highlight different opportunities for the expansion of the medicinal chemists' PROTAC toolbox towards heterobifunctional molecules, e.g. with biotin, fluorescent, hydrophobic and peptide tags.
- Steinebach, Christian,Sosi?, Izidor,Lindner, Stefanie,Bricelj, Ale?a,Kohl, Franziska,Ng, Yuen Lam Dora,Monschke, Marius,Wagner, Karl G.,Kr?nke, Jan,Gütschow, Michael
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p. 1037 - 1041
(2019/06/27)
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- Evaluation of linker length effects on a BET bromodomain probe
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Fueled by the therapeutic potential of the epigenetic machinery, BET bromodomains have seen high interest as drug targets. Herein, we introduce different linkers to a BET bromodomain benzodiazepine ligand (I-BET762) to gauge its implications in the develo
- Traquete, Rui,Henderson, Elizabeth,Picaud, Sarah,Cal, Pedro M. S. D.,Sieglitz, Florian,Rodrigues, Tiago,Oliveira, Rudi,Filippakopoulos, Panagis,Bernardes, Gon?alo J. L.
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supporting information
p. 10128 - 10131
(2019/08/30)
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- Thiazole orange – Spermine conjugate: A potent human telomerase inhibitor comparable to BRACO-19
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In this report, we synthesized a series of TO conjugates containing different amino side chains and investigated their binding to telomeric G-quadruplex DNA (G4) using several biophysical methods including fluorometric titration and thermal denaturation monitored by fluorescence and circular dichroism. The composition of side chains strongly affects the binding of these molecules to G-quadruplex DNA. Incorporation of amino side chains increases the binding affinity of TO toward G4 but has a minimal effect on its selectivity for G4 over duplex DNA. The plausible binding modes are a synergistic effect of end-stacking and groove interactions as indicated by docking studies. Inhibition of human telomerase activity by TO derivatives was determined in vitro by the TRAP assay. Several derivatives can selectively inhibit the activity of telomerase over DNA polymerase at low concentrations. More significantly, TO-spermine conjugate (16) exhibits a remarkable effect on telomerase inhibition in the submicromolar range, which is comparable to the inhibition effect of a well-known G4 ligand, BRACO-19. Our results here provide guidance of utilizing TO derivatives as a viable scaffold to design novel G4 ligands, G4 probes, and potent telomerase inhibitors.
- Wang, Siwen,Yang, Dazhou,Singh, Mandeep,Joo, Hyun,Rangel, Vanessa M.,Tran, Aaron,Phan, Erich,Xue, Liang
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- NOVEL NON-SYSTEMIC TGR5 AGONISTS
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The present invention relates to tricyclic compounds of formula (I) and formula (II), or a pharmaceutically acceptable salt thereof. The present tricyclic compounds are useful non-sytemic TGR5 agonists that can be used to treat diabetic diseases in human. The present invention provides a pharmaceutical composition containing tricyclic compounds of formula (I) and formula (II) and a method of making as well as a method of using same in treating patients inflicted with metabolic disorders by administering same. The compounds of the present invention may be used in combination with additional anti-diabetic drugs.
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Page/Page column 213
(2018/02/28)
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- Practical synthesis of a phthalimide-based Cereblon ligand to enable PROTAC development
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The use of small molecules to regulate cellular levels of specific proteins is poised to become a powerful technique in the coming years. Critical to the success of any project utilizing such an approach will be the ability to synthesize libraries of candidate small molecules for testing in cellular systems. Herein, we describe a practical synthesis of a phthalimide-based scaffold, which can be easily diversified to make Cereblon-targeting PROTACs. We demonstrate the effectiveness of this approach by synthesizing a ‘PROTAC toolbox’ of four amines which can be coupled to inhibitors in a straightforward manner.
- Lohbeck, Jasmin,Miller, Aubry K.
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supporting information
p. 5260 - 5262
(2016/10/30)
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- Fatty acid COX inhibitor derivatives and their uses
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The invention relates to fatty acid COX inhibitor derivatives; compositions comprising an effective amount of a fatty acid COX inhibitor derivative; and methods for treating or preventing a metabolic, autoimmune, inflammatory, or neurodegenerative disorde
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Page/Page column 53-54
(2016/01/09)
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- USE OF FATTY ACID NIACIN CONJUGATES FOR TREATING DISEASES
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The invention relates to fatty acid niacin conjugates; compositions comprising an effective amount of a fatty acid niacin conjugate; methods for treating or preventing an metabolic disease comprising the administration of an effective amount of a fatty acid niacin conjugate, and methods for treating or preventing an metabolic disease comprising the administration of an effective amount of a fatty acid niacin conjugate and another therapeutic agent.
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Paragraph 0329
(2014/07/22)
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- PAK INHIBITORS FOR THE TREATMENT OF CELL PROLIFERATIVE DISORDERS
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Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of cell proliferative disorders and/or CNS disorders.
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- FATTY ACID CONJUGATES OF STATIN AND FXR AGONISTS; COMPOSITIONS AND METHOD OF USES
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The invention relates to fatty acid statin conjugates and fatty acid FXR agonist conjugates; compositions comprising an effective amount of a fatty acid statin conjugate or a fatty acid FXR agonist conjugate; and methods for treating or preventing a metab
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Paragraph 0239
(2013/11/19)
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- METHODS OF LOWERING PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9)
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The invention relates to new methods of modulating cholesterol by inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) with fatty acid derivatives; and new methods for treating or preventing a metabolic disease comprising the administration of an effective amount of a fatty acid derivative. The present invention is also directed to fatty acid bioative derivatives and their use in the treatment of metabolic diseases.
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Paragraph 0241
(2014/01/07)
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- FATTY ACID GUANIDINE AND SALICYLATE GUANIDINE DERIVATIVES AND THEIR USES
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The invention relates to fatty acid guanidine or salicylate guanidine derivatives; compositions comprising an effective amount of a fatty acid guanidine or salicylate guanidine derivative; and methods for treating or preventing a metabolic disease compris
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Page/Page column 36-37
(2012/11/08)
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- FATTY ACID NON-FLUSHING NIACIN DERIVATIVES AND THEIR USES
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The invention relates to fatty non-flushing acid niacin derivatives; compositions comprising an effective amount of a fatty acid non-flushing niacin derivative; and methods for treating or preventing an metabolic disease comprising the administration of an effective amount of a fatty acid non-flushing niacin derivative.
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Page/Page column 31-32
(2012/10/08)
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- Fluorogenic protein labeling through photoinduced electron transfer-based BL-tag technology
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Keeping quenchers on a short leash: Shortening of the linker chain length combined with modification of the quencher moiety was found to improve fluorogenic probes useful for protein labeling by the mutant β-lactamase-tag (BL-tag) technology. The most eff
- Sadhu, Kalyan K.,Mizukami, Shin,Lanam, Carolyn R.,Kikuchi, Kazuya
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supporting information; scheme or table
p. 272 - 276
(2012/05/20)
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- Ring Closing and Related Methods and Intermediates
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Methods and intermediates useful for making compounds of the formula: and the preparation of compounds of Formula I, preferably including the formation of intermediate compounds of the formula:
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- PEPTIDE NUCLEIC ACID DERIVATIVES WITH GOOD CELL PENETRATION AND STRONG AFFINITY FOR NUCLEIC ACID
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The present invention provides a novel class of peptide nucleic acid derivatives, which show good cell penetration and strong binding affinity for nucleic acid.
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- FATTY ACID NIACIN CONJUGATES AND THEIR USES
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The invention relates to fatty acid niacin conjugates; compositions comprising an effective amount of a fatty acid niacin conjugate; and methods for treating or preventing an metabolic disease comprising the administration of an effective amount of a fatty acid niacin conjugate.
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Page/Page column 19
(2011/04/14)
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- FATTY ACID ACIFRAN DERIVATIVES AND THEIR USES
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The invention relates to fatty acid acifran derivatives; compositions comprising an effective amount of a fatty acid acifran derivative; and methods for treating or preventing an metabolic disease comprising the administration of an effective amount of a
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Page/Page column 21-22
(2011/04/24)
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- FATTY ACID FIBRATE DERIVATIVES AND THEIR USES
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The invention relates to fatty acid fibrate derivatives; compositions comprising an effective amount of a fatty acid fibrate derivative; and methods for treating or preventing an metabolic disease comprising the administration of an effective amount of a
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Page/Page column 34-35
(2011/04/24)
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- SUBSTITUTED THIOACETIC ACID SALICYLATE DERIVATIVES AND THEIR USES
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The invention relates to substituted thioacetic acid salicylate derivatives; compositions comprising an effective amount of a substituted thioacetic acid salicylate derivative; and methods for treating or preventing an metabolic disease comprising the adm
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Page/Page column 18
(2011/04/24)
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- FATTY ACID ACIPIMOX DERIVATIVES AND THEIR USES
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The invention relates to fatty acid acipimox derivatives; compositions comprising an effective amount of a fatty acid acipimox derivative; and methods for treating or preventing an metabolic disease comprising the administration of an effective amount of a fatty acid acipimox derivative.
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Page/Page column 19
(2011/04/24)
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- FATTY ACID FUMARATE DERIVATIVES AND THEIR USES
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The invention relates to Fatty Acid Fumarate Derivatives; compositions comprising an effective amount of a Fatty Acid Fumarate Derivative; and methods for treating or preventing cancer, a metabolic disorder or neurodegenerative disorder comprising the adm
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Page/Page column 36
(2011/08/03)
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- LIPOIC ACID ACYLATED SALICYLATE DERIVATIVES AND THEIR USES
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The invention relates to lipoic acid acylated salicylate derivatives; compositions comprising an effective amount of a lipoic acid acylated salicylate derivative; and methods for treating or preventing an metabolic disease comprising the administration of
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Page/Page column 29
(2011/04/24)
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- FATTY ACID MYCOPHENOLATE DERIVATIVES AND THEIR USES
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The invention relates to fatty acid mycophenolate derivatives; compositions comprising an effective amount of a fatty acid mycophenolate derivative; and methods for treating and preventing organ rejection and autoimmune diseases such as systemic lupus erythematosus, psoriasis and multiple sclerosis comprising the administration of an effective amount of a fatty acid mycophenolate derivative.
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Page/Page column 29
(2011/09/20)
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- Disassembly-driven turn-on fluorescent nanoprobes for selective protein detection
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"Switchable" fluorescent probes, which induce changes in the fluorescence properties (e.g., intensity and/or wavelength) only at the intended target protein, are particularly useful for selective protein detection or imaging. However, the strategy for designing such smart probes remains very limited. We report herein a novel mechanism for generating protein-specific "turn-on" fluorescent probes. Our approach uses an amphiphilic, self-assembling compound consisting of a fluorophore and a protein ligand. In the absence of target protein, the probe forms self-assembled aggregates in aqueous solution and displays almost no fluorescence because of efficient quenching. On the other hand, it emits bright fluorescence in response to the target protein through recognition-induced disassembly of the probe. On the basis of this strategy, we successfully developed three types of fluorescent probes that allow the detection of carbonic anhydrase, avidin, and trypsin via turn-on emission signals. It is anticipated that the present supramolecular approach may facilitate the development of new protein-specific switchable fluorescent probes that are useful for a wide range of applications, such as diagnosis and molecular imaging.
- Mizusawa, Keigo,Ishida, Yoshiyuki,Takaoka, Yousuke,Miyagawa, Masayoshi,Tsukiji, Shinya,Hamachi, Itaru
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supporting information; experimental part
p. 7291 - 7293
(2010/07/20)
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- PEPTIDE NUCLEIC ACID DERIVATIVES WITH GOOD CELL PENETRATION AND STRONG AFFINITY FOR NUCLEIC ACID
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The present invention provides a novel class of peptide nucleic acid derivatives, which show good cell penetration and strong binding affinity for nucleic acid.
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- THE TETRACYCLIC ANTHRAQUINONES POSSESSING ANTI-CANCER EFFECT
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The present invention provides aminoside tetracyclic anthraquinones represented by formula (I) or formula (II), wherein the piptides are introduced to connect tetracyclic anthraquinones and fatty acid saturated or unsaturated in order to make the anticancer agents to be absorbed and released selectively; meanwhile some water-solubility groups are also introduced into the branched chain, aminosaccharide and tetracyclic moiety of the compounds to improve the water-solubility. The present invention also provides the preparative method and the use thereof as pharmaceutically active components for treating the diseases cured by aminoside tetracyclic anthraquinone, for example cancer, such as intestines, liver, gastric, breast, lung, ovary, prostate, brain glioma, lymph, skin, pigment, thyroid gland, multiple bone marrow cancer and leukemia.
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Page/Page column 15
(2009/12/07)
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- TETRACYCLIC ANTHRAQUINONES POSSESSING ANTI-CANCER PROPERTIES
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The present invention provides aminoside tetracyclic anthraquinones represented by formula (I) or formula (II), wherein the peptides are introduced to connect tetracyclic anthraquinones and fatty acid saturated or unsaturated in order to make the anticancer agents to be absorbed and released selectively; meanwhile some water-solubility groups are also introduced into the branched chain, aminosaccharide and tetracyclic moiety of the compounds to improve the water-solubility. The present invention also provides the preparative method and the use thereof as pharmaceutically active components for treating the diseases cured by aminoside tetracyclic anthraquinone, for example cancer, such as intestines, liver, gastric, breast, lung, ovary, prostate, brain glioma, lymph, skin, pigment, thyroid gland, multiple bone marrow cancer and leukemia.
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Page/Page column 10
(2010/01/31)
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- Method of conjugating therapeutic compounds to cell targeting moieties via metal complexes
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The present invention relates to a cell-targeting complex comprising a targeting moiety and a deliverable compound, wherein said targeting moiety and said deliverable compound are joined by means of a (transition) metal ion complex having at least a first reactive moiety for forming a coordination bond with a reactive site of said targeting moiety and having at least a second reactive moiety for forming a coordination bond with a reactive site of said deliverable compound, and wherein said deliverable compound is a therapeutic compound.
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Page/Page column 17
(2010/11/25)
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- Design and synthesis of novel photoaffinity reagents for labeling VEGF receptor tyrosine kinases
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Novel biotin-tagged photoaffinity probes based on a trifunctional tertiary amine scaffold were synthesized and evaluated as vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors. Probes 3a-c inhibit VEGF induced proliferation in HUVE cells, w
- Han, Sun-Young,Choi, Seo Hyun,Kim, Myung Hee,Lee, Woo Ghil,Kim, Seong Hwan,Min, Yong Ki,Kim, Bum Tae
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p. 2915 - 2919
(2007/10/03)
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- Sulfonamido ether substituted imidazoquinolines
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Imidazoquinoline and tetrahydroimidazoquinoline compounds that contain ether and sulfonamide or sulfamide functionality at the 1-position are useful as immune response modifiers. The compounds and compositions of the invention can induce the biosynthesis of various cytokines and are useful in the treatment of a variety of conditions including viral diseases and neoplastic diseases.
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- Ether substituted imidazopyridines
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Imidazopyridine compounds that contain an ether or thioether functionality at the 1-position are useful as immune response modifiers. The compounds and compositions of the invention can induce the biosynthesis of various cytokines and are useful in the treatment of a variety of conditions including viral diseases and neoplastic diseases. Methods of preparing the compounds and intermediates useful in the preparation of the compounds are also disclosed.
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- Amido ether substituted imidazoquinolines
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Imidazoquinoline and tetrahydroimidazoquinoline compounds that contain ether and amide functionality at the 1-position are useful as immune response modifiers. The compounds and compositions of the invention can induce the biosynthesis of various cytokines and are useful in the treatment of a variety of conditions including viral diseases and neoplastic diseases.
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Page column 23
(2008/06/13)
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- Urea substituted imidazoquinoline ethers
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Imidazoquinoline and tetrahydroimidazoquinoline compounds that contain ether and urea functionality at the 1-position are useful as immune response modifiers. The compounds and compositions of the invention can induce the biosynthesis of various cytokines and are useful in the treatment of a variety of conditions including viral diseases and neoplastic diseases.
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- Sulfonamido ether substituted imidazoquinolines
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Imidazoquinoline and tetrahydroimidazoquinoline compounds that contain ether and sulfonamide or sulfamide functionality at the 1-position are useful as immune response modifiers. The compounds and compositions of the invention can induce the biosynthesis of various cytokines and are useful in the treatment of a variety of conditions including viral diseases and neoplastic diseases.
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- Amido ether substituted imidazoquinolines
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Imidazoquinoline and tetrahydroimidazoquinoline compounds that contain ether and amide functionality at the 1-position are useful as immune response modifiers. The compounds and compositions of the invention can induce the biosynthesis of various cytokines and are useful in the treatment of a variety of conditions including viral diseases and neoplastic diseases.
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- Urea substituted imidazoquinoline ethers
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Imidazoquinoline and tetrahydroimidazoquinoline compounds that contain ether and urea functionality at the 1-position are useful as immune response modifiers. The compounds and compositions of the invention can induce the biosynthesis of various cytokines and are useful in the treatment of a variety of conditions including viral diseases and neoplastic diseases.
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Page column 21
(2008/06/13)
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- Design of a neutral macrocyclic ionophore: Synthesis and binding properties for nitrate and bromide anions
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A macrocyclic neutral ionophore 8 (X = O) capable of binding weakly coordinating anions such as nitrate and bromide in DMSO solution has been designed by a stepwise, deductive approach. The optimum geometrical arrangement of the hydrogen bond donor sites
- Herges, Rainer,Dikmans, Anton,Jana, Umasish,Koehler, Felix,Jones, Peter G.,Dix, Ina,Fricke, Tom,Koenig, Burkhard
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p. 3004 - 3014
(2007/10/03)
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- Chelating agents
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A bifunctional chelating agent for joining an antibody or antibody fragment and a metallic radionuclide is disclosed. The agent consists of a derivative of 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid or a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, an organic linking radical which optionally contains a cleavable group, and a function capable of reacting with a site on a protein. Radiodiagnostic or radiotherapeutic precursors comprising an antibody or antibody fragment and the above-described bifunctional chelating agent and radiodiagnostic or radiotherapeutic agent comprising a metallic radionuclide and the above mentioned precursor are also disclosed.
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