- Dendrimer-based transient supramolecular networks
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Association of a 16-fold excess of a monodisperse telechelic oligo(THF) (Mw = 1270 g/mol) containing two end groups that selectively bind to the 32 binding sites of a fifth generation dendritic host (Mw = 18511 g/mol and radius R h = 2.4 nm) re
- Versteegen, Ron M.,Van Beek,Sijbesma, Rint P.,Vlassopoulos, Dimitris,Fytas, George,Meijer
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Read Online
- BRM TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE
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The present disclosure relates to bifunctional compounds, which find utility as modulators of SMARCA2 or BRM (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand that binds to the Von Hippel-Lindau 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 or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 1000-1001
(2019/10/23)
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- A Protocol for Direct Stereospecific Amination of Primary, Secondary, and Tertiary Alkylboronic Esters
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The direct, stereospecific amination of alkylboronic and borinic esters can be conducted by treatment of the organoboron compound with methoxyamine and potassium tert -butoxide. In addition to being stereospecific, this process also enables the direct amination of tertiary boronic esters in an efficient fashion.
- Edelstein, Emma K.,Grote, Andrea C.,Palkowitz, Maximilian D.,Morken, James P.
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supporting information
p. 1749 - 1752
(2018/06/26)
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- Ligand-biased and probe-dependent modulation of chemokine receptor CXCR3 signaling by negative allosteric modulators
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Over the last decade, functional selectivity (or ligand bias) has evolved from being a peculiar phenomenon to being recognized as an essential feature of synthetic ligands that target G protein-coupled receptors (GPCRs). The CXC chemokine receptor 3 (CXCR3) is an outstanding platform to study various aspects of biased signaling, because nature itself uses functional selectivity to manipulate receptor signaling. At the same time, CXCR3 is an attractive therapeutic target in the treatment of autoimmune diseases and cancer. Herein we report the discovery of an 8-azaquinazolinone derivative (N-{1-[3-(4-ethoxy-phenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-2-yl]ethyl}-4-(4-fluorobutoxy)-N-[(1-methylpiperidin-4-yl)methyl]butanamide, 1b) that can inhibit CXC chemokine 11 (CXCL11)-dependent G protein activation over β-arrestin recruitment with 187-fold selectivity. This compound also demonstrates probe-dependent activity, that is, it inhibits CXCL11- over CXCL10-mediated G protein activation with 12-fold selectivity. Together with a previously reported biased negative allosteric modulator from our group, the present study provides additional information on the molecular requirements for allosteric modulation of CXCR3.
- Bernat, Viachaslau,Brox, Regine,Heinrich, Markus R.,Auberson, Yves P.,Tschammer, Nuska
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supporting information
p. 566 - 574
(2015/03/13)
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- Light-mediated deoxygenation of alcohols with a dimeric gold catalyst
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A new protocol for the reductive deoxygenation of primary alcohols was explored. This photo-mediated method combines a novel approach to bromination of alcohols merged with the powerful reducing capability of [Au2(dppm)2]Cl2 [dppm = 1,1-bis(diphenylphosphino)methane] as a photoredox catalyst. The highly efficient methods discussed are marked by the use of UVA light-emitting diodes, which have significantly reduced reaction times and lowered setup cost.
- McCallum, Terry,Slavko, Ekaterina,Morin, Mathieu,Barriault, Louis
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supporting information
p. 81 - 85
(2015/02/18)
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- Tricyclic challenges: Synthetic approaches toward dodecahydrocyclopenta[a] indenes
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Tetrahydrospiro[1,3-dioxolane-2,1′-pentalen]-4′-ones were stereoselectively converted to either (cis,anti,cis)- or (cis,syn)-linear dodecahydrocyclopenta[a]indene isomers employing a 1,4- or 1,2-conjugate addition of organometallic reagents and an intramolecular aldol reaction as the key steps. The relative configuration of the products was determined by X-ray crystal structure analysis and 1D NOE spectroscopy.
- Krebs, Michael,Kalinowski, Matth?us,Frey, Wolfgang,Claasen, Birgit,Baro, Angelika,Schobert, Rainer,Laschat, Sabine
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p. 7373 - 7380
(2013/08/23)
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- Synthesis and evaluation of cyclic RGD-boron cluster conjugates to develop tumor-selective boron carriers for boron neutron capture therapy
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Boron-containing agents play a key role in successful boron neutron capture therapy (BNCT). Icosahedral boron cluster-Arg-Gly-Asp (RGD) peptide conjugates were designed, synthesized, and evaluated for the biodistribution to develop tumor-selective boron c
- Kimura, Sadaaki,Masunaga, Shin-Ichiro,Harada, Tomohiro,Kawamura, Yasuo,Ueda, Satoshi,Okuda, Kensuke,Nagasawa, Hideko
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supporting information; experimental part
p. 1721 - 1728
(2011/04/18)
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- A new strategy for the stereoselective synthesis of 2,2′-bipyrrolidines
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A new strategy for the stereoselective synthesis of the 2,2′-bipyrrolidine scaffold is presented using a metathesis reaction followed by asymmetric dihydroxylation for the introduction of the stereogenic elements. This straightforward high-yielding process is suitable for application to the synthesis of additional heterocycles.
- Gresser, Mary J.,Keller, Paul A.,Wales, Steven M.
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scheme or table
p. 4899 - 4902
(2009/12/05)
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- Biomimetic design of reversibly unfolding cross-linker to enhance mechanical properties of 3D network polymers
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We report here a biomimetic design of a reversibly unfolding modular cross-linker to enhance mechanical properties of 3D network polymers. The inspiration comes from the modular biopolymers observed in nature. A cyclic modular cross-linker based on the quadruple hydrogen bonding 4-ureido-2-pyrimidone (UPy) motif was synthesized via multistep organic synthesis. The modular cross-linker was incorporated into poly(n-butyl acrylate) by free radical polymerization. Stress-strain measurements show that the samples containing our modular cross-linker exhibit significantly enhanced mechanical properties over the control samples. Most strikingly, with increasing cross-linker density, both modulus and tensile strength are significantly improved without sacrificing extensibility. The enhanced tensile properties are attributed to the increased energy dissipating ability of the reversibly unfolding cross-linker. This introduces a novel biomimetic concept to enhance network mechanical properties through design of molecularly engineered cross-linkers. Copyright
- Kushner, Aaron M.,Gabuchian, Vahe,Johnson, Evan G.,Guan, Zhibin
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p. 14110 - 14111
(2008/09/17)
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- Combination preparation of estrogen and anti-estrogen
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The invention describes a combination preparation of an oestrogen and an antioestrogen, characterized in that the oestrogen is selected from the group consisting of 17-β-oestradiol, 17-α-ethynyloestradiol, oestriol, oestrone, oestrone sulphate, oestrogen sulphamates, 17α-oestradiol, mestranol, stilboestrol and naturally conjugated oestrogens and in that the antioestrogen is a substituted 7α-(ξ-aminoalkyl)oestratriene of the general formula I The combination preparation according to the invention can be used for hormone substitution therapy.
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- 11BETA-HALOGEN-7ALPHA-SUBSTITUTED ESTRATRIENES, METOD FOR PRODUCING PHARMACEUTICAL PREPARATIONS CONTAINING SAID 11BETA-HALOGEN-7ALPHA- SUBSTITUTED ESTRATRIENES AND USE OF THE SAME FOR PRODUCING MEDICAMENTS
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This invention describes the new 11β-halogen-7α-substituted estratrienes of general formula I in which R11 is a fluorine or chlorine atom, and the other substituents have the meanings that are explained in more detail in the description. The compounds have antiestrogenic properties or tissue-selective estrogenic properties and are suitable for the production of pharmaceutical agents.
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- BENZOIC ACID COMPOUNDS AND USE THEREOF AS MEDICAMENTS
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Benzoic acid compounds of the formula STR1 wherein each symbol is as defined in the specification, optical isomers thereof and pharmaceutically acceptable salts thereof; pharmaceutical composition comprising this compound and pharmaceutically acceptable additive; and serotonin 4 receptor agonists, gastrointestinal prokinetic agents and therapeutic agents for various gastrointestinal diseases, which comprise this compound as active ingredient. The compounds of the present invention have high and selective affinity for serotonin 4 receptor, and show agonistic effects thereon. Accordingly, they are useful medications for the prophylaxis and treatment of various gastrointestinal diseases, central nervous disorders, cardiac function disorders, urinary diseases, and the like, as well as useful anti-nociceptors for analgesic use which increase threshold of pain.
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- BENZOIC ACID COMPOUNDS AND MEDICINAL USE THEREOF
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A benzoic acid compound of the formula wherein each symbol is as defined in the specification, an optical isomer thereof and a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprising this compound and a pharmaceutically acceptable additive, a serotonin 4 receptor agonist comprising this compound as an active ingredient, a gastrointestinal prokinetic agent and a therapeutic agent for gastrointestinal diseases. The compound of the present invention shows selective and high affinity for serotonin 4 receptors, activates same, is useful as a pharmaceutical agent for the prophylaxis and treatment of gastrointestinal diseases (e.g., reflux esophagitis; gastroesophageal reflux such as that accompanying cystic fibrosis; Barrett syndrome; intestinal pseudoileus; acute or chronic gastritis; gastric or duodenal ulcer; Crohn's disease; non-ulcer dyspepsia; ulcerative colitis; postgastrectomy syndrome; postoperative digestive function failure; delayed gastric emptying caused by gastric neurosis, gastroptosis, diabetes, and the like; gastrointestinal disorders such as indigestion, meteorism, abdominal indefinite complaint, and the like; constipation such as atonic constipation, chronic constipation, and that caused by spinal cord injury, pelvic diaphragm failure and the like; and irritable bowel syndrome), central nervous disorders (e.g., schizophrenia, depression, anxiety, disturbance of memory and dementia), cardiac function disorders (e.g., cardiac failure and myocardial ischemia), urinary diseases (e.g., dysuria caused by urinary obstruction, ureterolith, prostatomegaly, spinal cord injury, pelvic diaphragm failure, etc.), and shows superior absorption.
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- Enantiopure N-Acyldihydropyridones as Synthetic Intermediates: Asymmetric Syntheses of Indolizidine Alkaloids (-)-205A, (-)-207A, and (-)-235B
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Concise asymmetric syntheses of indolizidine alkaloids (-)-205A, (-)-207A, and (-)-235B were accomplished with a high degree of stereocontrol in eleven steps. Addition of 4-(1-butenyl)-magnesium bromide to 1-acylpyridinium salt 5, prepared in situ from 4-methoxy-3-(triisopropylsilyl)-pyridine and the chloroformate of (+)trans-2-(α-cumyl)cyclohexanol, gave a 91% yield of diastereomerically pure dihydropyridone 6. Oxidative cleavage of 6 and subsequent reduction provided alcohol 7 in 81% yield. Removal of the chiral auxilliary and TIPS group (NaOMe; 10% HCl), N-acylation with BnOCOCCl, and treatment with NCS/Ph3P gave chloride 10. Methylation at C-3, copper-mediated conjugate addition of 4-(benzyloxy)butylmagnesium bromide, and vinyl triflate formation provided 13 in a stereoselective fashion. Catalytic reduction of the vinyl triflate moiety, simultaneous cleavage of the benzyl ether and Cbz groups, and cyclization to give amino alcohol 14 was effected via a one-pot reaction. Oxidation of 14 with the Dess-Martin reagent gave a 97% yield of amino aldehyde 4. Synthesis of each of the three title alkaloids was accomplished in one step from 4. The Seyferth-Gilbert reaction provided a 41% yield of (-)-205A. The appropriate Wittig olefination of 4 gave indolizidines (-)-207A and (-)-235B in 70% and 86% yield, respectively.
- Comins, Daniel L.,LaMunyon, Donald H.,Chen, Xinghai
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p. 8182 - 8187
(2007/10/03)
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- Immunological detection of organophosphates
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A compound useful for forming immunoconjugates used in the detection of organophosphate pesticides is provided. The compound has the formula STR1 wherein X is selected from the group consisting of R--O--, R--S-- and R--NH--, where R is an optionally subst
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- 9-(SULFOXIMINOALKYL)GUANINE NUCLEOSIDES AS POTENTIAL ANTIHERPETIC AGENTS
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A novel series of guanine nucleoside analogues 5-8 which contain a C-terminal sulfoximine have been synthesized.Key features of the synthesis include 1) the successful application of the trifluoroacetyl functional group as a stable, base-labile protecting group for the sulfoximine nitrogen and 2) the Mitsunobu-type coupling of alcohols 14 and 18-20 with purine 15.
- Dolle, Roland E.,McNair, David
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p. 133 - 136
(2007/10/02)
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- Use of Polyoxetane Resin-Supported Quaternary Onium Salts as a Polymeric Phase-Transfer Catalyst for Preparing Ethers from Hydroxy Compounds and Alkyl Halides
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As a polymer support for preparing polymeric phase-transfer catalysts (PTC), soft, moderately polar polyoxetane resins were employed which were synthesized by a cationic ring-opening copolymerization of oxetanes Br(CH2)nOCH2-X with bisoxetanes X-CH2O(CH2)nOCH2-X, where X=3-methyl-3-oxetanyl and n=4 or 6.In a few cases of those polymerizations, 3-(2-oxadecyl)-3-methyloxetane was used as a comonomer with a lipophilic pendant.The terminal bromine of the pendant groups of such polyoxetane resins was quaternized with tributylamine or tributylphosphine in DMF in order to examine the phase-transfer catalyzing ability of the resultant quaternary onium bromides in the etherification reaction between alkyl halides and alcohols or phenols.These reactions gave the desired products in fairly good yields within reaction periods of 1-3 h, indicating that the catalytic activities of those PTCs are comparable to that of tetrabutylammonium bromide.A fairly high catalytic activity of the polymeric PTC was observed at each of ten stages in a process using the polymeric PTC repeatedly for the etherification reaction of 3-hydroxymethyl-3-methyloxethane with 1,4-dibromobutane.
- Motoi, Masatoshi,Shimamura, Katsuhiko,Shimamura, Chikako,Muramoto, Satoru,Kanoh, Shigeyoshi,Suda, Hiroshi
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p. 2553 - 2561
(2007/10/02)
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- Selective Cleavage of Dimethylhydrazones to the Carbonyl Compounds Using Silica Gel and its Application in the Synthesis of (Z)-9-Tetradecenyl Acetate
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A new method for the selective hydrolytic cleavage of dimethylhydrazones consists of treatment of the hydrazones with silica gel (pH 6.80) in wet tetrahydrofuran.Utilizing this method as one of the key steps, (Z)-9-tetradecenyl acetate, the pheromone of Spodoptera frugiperda, was synthesized.
- Mitra, R. B.,Reddy, G. Bhaskar
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p. 694 - 698
(2007/10/02)
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- MECHANISMUS DER PROTONKATALYSIERTEN GASPHASENDEHYDRATISIERUNG VON FURFURYLALKOHOL
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The gas phase proton catalysed water elimination of tetrahydrofurfuryl alcohol (1) gives exclusively the ring-enlarged oxonium-ion 12.There is no experimental indication for the generation of 11 via a -hydrogen migration.From the analysis of appropriately 13C-labelled precursors in combination with collisional activation mass spectrometry the mechanism for the ring-enlargement has been derived, clearly indicating that the oxygen/carbon bond is cleaved.A comparison of the experimental results with computational investigation (ab initio molecular orbital calculations at the 4-31G level) suggests that free tetrahydrofurfuryl cation 7 is not generated in the gas phase solvolysis.The elimination of H2O from the protonated molecule of 1 is a process characterised by anchimeric assistance of the ether oxygen 15.
- Thies, H.,Wolfschuetz, R.,Frenking, G.,Schmidt, J.,Schwarz, H.
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p. 1647 - 1656
(2007/10/02)
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