- Semi-aromatic biobased polyesters derived from lignin and cyclic carbonates
-
The synthesis of biobased aromatic polyesters from lignin-derived monomers has become well described in the literature, but robust extrusion, thermomechanical, tensile and degradation studies of these materials is lacking. In this work, we have systematically investigated the mechanical and biodegradation properties of semi-aromatic polyesters that can potentially be derived from lignin. AB monomers were synthesized from reduced analogues of coumaric, ferulic, and sinapic acids along with cyclic carbonates, where the synthetic methodology was assessed using E-Factor and EcoScale. Polymerization yielded both semi-crystalline and amorphous polyesters with mechanical properties varying over three orders of magnitude. Detailed characterization revealed a wide array of properties including a highly ductile thermoplastic, a strong and rigid thermoplastic, and an elastomer. Composting biodegradation tests showed both degradable and nondegradable polymers can be achieved in this class. This work demonstrates the versatility of this class of polymers and illustrates their potential to replace non-sustainably derived plastics. This journal is
- Horn, Jessica,Locklin, Jason,Ring, John,White, Evan M.,Winfield, Demichael
-
supporting information
p. 9658 - 9668
(2021/12/09)
-
- Preparation method of iprolol hydrochloride
-
The invention provides a preparation method of iprolol hydrochloride. The method comprises the following steps: reacting thionyl chloride and methanol to prepare methyl chloride. Methyl p-hydroxyphenylpropionic acid methyl ester is prepared by substitution reaction of p-hydroxyphenylpropionic acid and methyl chlorite. The etherification reaction of methyl hydroxy phenylpropionic acid methyl ester and epichlorohydrin is prepared to obtain 3 - [4 - (2, 3 - epoxypropoxy] phenylpropionic acid methyl ester. 3 - [4 - (2, 3 - Epoxypropoxy] phenylpropionic acid methyl ester and isopropylamine undergo amination reaction to prepare the ilomolol. Diaprolol hydrochloride and hydrochlorination of hydrogen chloride to obtain ilomolol hydrochlorideThe method has the advantages of easily available raw materials, low cost and simple preparation method. The target product has high yield, high purity and market competitiveness.
- -
-
Paragraph 0053-0055; 0074
(2021/10/11)
-
- A 2-formylphenylboronic acid (2FPBA)-maleimide crosslinker: a versatile platform for Cys-peptide-hydrazine conjugation and interplay
-
In this work, we describe the preparation of a heterobifunctional 2-formylphenylboronic acid (2-FPBA)-maleimide crosslinker and explore its versatility in the preparation of various bioconjugates. We demonstrate the straightforward attachment of hydrazine payloads to cysteine residues in peptides, as well as the crosslinking of different thiol-bearing peptides or payloads withN-terminal cysteine peptides. Importantly, the dynamic nature of the 2-FPBA handle enables an interplay between the thiazolidine and diazaborine forms, which allows obtaining various products controlled by (and in some cases independent of) the order of addition of the components.
- António, Jo?o P. M.,Faustino, Hélio,Gois, Pedro M. P.
-
p. 6221 - 6226
(2021/07/28)
-
- Diazaborines Are a Versatile Platform to Develop ROS-Responsive Antibody Drug Conjugates**
-
Antibody–drug conjugates (ADCs) are a new class of therapeutics that combine the lethality of potent cytotoxic drugs with the targeting ability of antibodies to selectively deliver drugs to cancer cells. In this study we show for the first time the synthesis of a reactive-oxygen-species (ROS)-responsive ADC (VL-DAB31-SN-38) that is highly selective and cytotoxic to B-cell lymphoma (CLBL-1 cell line, IC50 value of 54.1 nM). The synthesis of this ADC was possible due to the discovery that diazaborines (DABs) are a very effective ROS-responsive unit that are also very stable in buffer and in plasma. DFT calculations performed on this system revealed a favorable energetic profile (ΔGR=?74.3 kcal mol?1) similar to the oxidation mechanism of aromatic boronic acids. DABs’ very fast formation rate and modularity enabled the construction of different ROS-responsive linkers featuring self-immolative modules, bioorthogonal functions, and bioconjugation handles. These structures were used in the site-selective functionalization of a VL antibody domain and in the construction of the homogeneous ADC.
- Aguiar, Sandra I.,André, Ana S.,António, Jo?o P. M.,Bernardes, Gon?alo J. L.,Carvalho, Joana Inês,Dias, Joana N. R.,Faustino, Hélio,Gois, Pedro M. P.,Lopes, Ricardo M. R. M.,Veiros, Luis F.,da Silva, Frederico A.
-
supporting information
p. 25914 - 25921
(2021/11/09)
-
- Preparation process of high-purity iprolol hydrochloride
-
The invention belongs to the technical field of organic chemistry and medical chemistry. In particular, the invention relates to a preparation process of high-purity iprolol hydrochloride. To the preparation process, p-hydroxyphenylpropionic acid and methanol are subjected to esterification reaction under the action of first catalyst, and the p-hydroxyphenylpropionic acid methyl ester and epoxy chloropropane are reacted under the action of second catalyst to obtain 3 - [4 - (2, 3 - epoxypropoxy) phenyl] propanoate, and then, methyl propionate is added in the methyl alcohol solvent in this order to obtain methyl p-hydroxybenzenepropanoic acid methyl ester and then in a methanolic solvent, and then the 3 - preparation 4 - process 2 can 3 - be carried out. The crude hydrochloride and hydrogen chloride is subjected to heating dissolution, activated carbon decoloration, cooling crystallization and centrifugation and drying operation in sequence to obtain final high-purity ilomolol hydrochloride with a total impurity lower than 0.5% and a single unknown single impurity lower than 0.05%.
- -
-
Paragraph 0031
(2021/11/19)
-
- Synthesis of HBED–CC–tris(tert-butyl ester) using a solid phase and a microwave reactor
-
N,N′-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid (HBED-CC) belongs to the acyclic, bifunctional complexing compounds used mainly for radiolabeling with gallium-68 (68Ga). Due to the high stability of the 68Ga3+complex, HBED-CC is well known for its rapid and efficient labeling at ambient temperature and the high stability of the complexes in vivo. The HBED-CC chelator in combination with a PSMA (Prostate Specific Membrane Antigen) inhibitor and labeled with isotope of gallium is an important tool for diagnosing the stage of cancer in patients with prostate cancer. Many HBED-CC derivatives have been described in the literature, but one of the most commonly used is 3-(3-{[(2-{[5-(2-tert-butoxycarbonylethyl)-2-hydroxybenzyl]-tert-butoxycarbonylmethylamino}-ethyl)-tert-butoxy-carbonylmethylamino]-methyl}-4-hydroxyphenyl)propionic acid (HBED–CC–tris(tert-butyl ester)). This compound is very expensive and commercially limited. Therefore this work describes an innovative method of synthesis on solid phase using of a microwave reactor. Optimization of the reaction allowed to obtain HBED-CC-tris(tert-butyl ester) with high purity and yield.
- Jerzyk,Kludkiewicz,Pijarowska-Kruszyna,Jaron,Maurin,Sikora,Kordowski,Garnuszek
-
-
- A General Organocatalytic System for Electron Donor-Acceptor Complex Photoactivation and Its Use in Radical Processes
-
We report herein a modular class of organic catalysts that, acting as donors, can readily form photoactive electron donor-acceptor (EDA) complexes with a variety of radical precursors. Excitation with visible light generates open-shell intermediates under mild conditions, including nonstabilized carbon radicals and nitrogen-centered radicals. The modular nature of the commercially available xanthogenate and dithiocarbamate anion organocatalysts offers a versatile EDA complex catalytic platform for developing mechanistically distinct radical reactions, encompassing redox-neutral and net-reductive processes. Mechanistic investigations, by means of quantum yield determination, established that a closed catalytic cycle is operational for all of the developed radical processes, highlighting the ability of the organic catalysts to turn over and iteratively drive every catalytic cycle. We also demonstrate how the catalysts' stability and the method's high functional group tolerance could be advantageous for the direct radical functionalization of abundant functional groups, including aliphatic carboxylic acids and amines, and for applications in the late-stage elaboration of biorelevant compounds and enantioselective radical catalysis.
- De Pedro Beato, Eduardo,Melchiorre, Paolo,Spinnato, Davide,Zhou, Wei
-
supporting information
p. 12304 - 12314
(2021/08/20)
-
- Reduction of Electron-Deficient Alkenes Enabled by a Photoinduced Hydrogen Atom Transfer
-
Direct hydrogen atom transfer from a photoredox-generated Hantzsch ester radical cation to electron-deficient alkenes has enabled the development of an efficient formal hydrogenation under mild, operationally simple conditions. The HAT-driven mechanism is supported by experimental and computational studies. The reaction is applied to a variety of cinnamate derivatives and related structures, irrespective of the presence of electron-donating or electron-withdrawing substituents in the aromatic ring and with good functional group compatibility. (Figure presented.).
- Larionova, Natalia A.,Ondozabal, Jun Miyatake,Cambeiro, Xacobe C.
-
p. 558 - 564
(2020/12/07)
-
- Novel drug isolated from mistletoe (1: E,4 E)-1,7-bis(4-hydroxyphenyl)hepta-1,4-dien-3-one for potential treatment of various cancers: Synthesis, pharmacokinetics and pharmacodynamics
-
(1E,4E)-1,7-Bis(4-hydroxyphenyl)hepta-1,4-dien-3-one (DHDK) is a novel curcuminoid analogue isolated from mistletoe. DHDK exhibits better anti-tumour activity, higher bioavailability and superior stability than curcumin. DHDK is difficult to isolate from Viscum coloratum, but it can be synthesised. MTT (methylthiazolyldiphenyl tetrazolium bromide) assay was used to evaluate the in vitro cytotoxic activity of synthesised DHDK on 12 cancer cell lines. Results showed that DHDK exhibited excellent potential as an anticancer agent, especially for breast and lung cancer. Efficacy was further evaluated in vivo by using MCF-7 breast cancer models. DHDK showed a dose-dependent relationship without weight reduction, mortality growth inhibition or tissue toxicity. Pharmacokinetics and tissue distribution statistics were determined by LC-ESI-MS/MS. This work provided preliminary data on this natural compound and could open up new prospects for changing related parameters to improve drug efficacy.
- Hong, Jing,Meng, Lin,Qin, Feng,Yu, Peipei,Yu, Zhiguo,Zhang, Zhaoyan,Zhao, Yunli,Zhou, Ceng
-
p. 27794 - 27804
(2020/08/17)
-
- Computer-Aided Fragment Growing Strategies to Design Dual Inhibitors of Soluble Epoxide Hydrolase and LTA4 Hydrolase
-
Multitarget ligands are interesting candidates for drug discovery and development due to improved safety and efficacy. However, rational design and optimization of multitarget ligands is tedious because affinity optimization for two or more targets has to be performed simultaneously. In this study, we demonstrate that, given a molecular fragment, which binds to two targets of interest, computer-aided fragment growing can be applied to optimize compound potency, relying on either ligand- or structure-derived information. This methodology is applied to the design of dual inhibitors of soluble epoxide hydrolase and leukotriene A4 hydrolase.
- Hefke, Lena,Hiesinger, Kerstin,Kramer, Jan S.,Proschak, Ewgenij,Zhu, W. Felix
-
supporting information
p. 1244 - 1249
(2020/07/04)
-
- Exploring bulky natural and natural-like periphery in the design of p-(benzyloxy)phenylpropionic acid agonists of free fatty acid receptor 1 (GPR40)
-
Six derivatives of 3-phenylpropionic acid bearing various natural and natural-like, spatially defined peripheral motifs have been synthesized and evaluated in vitro for free fatty acid receptor 1 (FFA1) activation. Two frontrunner compounds (bearing a bornyl and cytosine groups) were evaluated in an oral glucose tolerance test in mice where both demonstrated the ability to sustain blood glucose levels following a glucose challenge. The bornyl compound displayed a somewhat superior, dose-dependent efficacy and, therefore, can be regarded as a lead compounds for further development as a therapeutic agent for type 2 diabetes mellitus. Its high affinity to FFA1 was rationalized by docking experiments.
- Gureev, Maxim,Krasavin, Mikhail,Kuranov, Sergey O.,Luzina, Olga A.,Onopchenko, Oleksandra,Pishel, Iryna,Salakhutdinov, Nariman F.,Zozulya, Sergey
-
-
- Engineering Boron Hot Spots for the Site-Selective Installation of Iminoboronates on Peptide Chains
-
Boronic acids (BAs) are a promising bioconjugation function to design dynamic materials as they can establish reversible covalent bonds with oxygen/nitrogen nucleophiles that respond to different pH, ROS, carbohydrates and glutathione levels. However, the dynamic nature of these bonds also limits the control over the stability and site-selectivity of the bioconjugation, which ultimately leads to heterogeneous conjugates with poor stability under physiological conditions. Here we disclose a new strategy to install BAs on peptide chains. In this study, a “boron hot spot“ based on the 3-hydroxyquinolin-2(1H)-one scaffold was developed and upon installation on a peptide N-terminal cysteine, enables the site-selective formation of iminoboronates with 2-formyl-phenyl boronic acids (Ka of 58128±2 m?1). The reaction is selective in the presence of competing lysine ?-amino groups, and the resulting iminoboronates, displayed improved stability in buffers solutions and a cleavable profile in the presence of glutathione. Once developed, the methodology was used to prepare cleavable fluorescent conjugates with a laminin fragment, which enabled the validation of the 67LR receptor as a target to deliver cargo to cancer HT29 cells.
- Russo, Roberto,Padanha, Rita,Fernandes, Fábio,Veiros, Luis F.,Corzana, Francisco,Gois, Pedro M. P.
-
supporting information
p. 15226 - 15231
(2020/10/20)
-
- Preparation method of esmolol hydrochloride intermediate
-
The invention belongs to the field of organic synthesis of medicines, and particularly relates to a preparation method of a medicine esmolol hydrochloride intermediate for treating hypertension. The synthesis route provided by the invention comprises the following steps: reacting p-bromophenol with methyl acrylate in the presence of a palladium catalyst and a phosphine ligand to generate 3-(4-hydroxyphenyl) methyl acrylate; and hydrogenating the generated 3-(4-hydroxyphenyl) methyl acrylate in the presence of a palladium-carbon catalyst to obtain a target product methyl 4-hydroxyphenylpropionate. The method has the advantages of short reaction steps, cheap and accessible raw materials, simple technique and convenience of operation, and does not need special reaction conditions, thereby being more suitable for industrial production.
- -
-
Paragraph 0041; 0044-0046; 0049-0050
(2020/09/16)
-
- Complex of bifunctional connecting agent realizing core coordination with carbonyl metal and preparation method thereof
-
The invention relates to a complex of a bifunctional connecting agent realizing core coordination with carbonyl metal and a preparation method thereof, and belongs to the technical field of radiopharmaceutical chemistry. The bifunctional connecting agent is N,N'-bi[2-hydroxyl-5-( propyloic) benzyl] ethylenediamine-N,N'-oxalic acid, and has a structure shown in the description, wherein at least onein R1 and R2 is a targeted small molecule or polypeptide or protein big molecule; the metal is Tc or Re. The carbonyl Tc/Re core marked HBED-CC complex is successfully obtained for the first time, different nuclide (68Ga, 99mTc/Re) marks of the same marking precursors can be realized; by aiming at the mutual supplementation of two development modes (PET/SPECT) in the same target point, the 188/186Re complex can be used for radioactive therapy medicine study. A novel idea is provided for the development of a Tc-99m single photon radioactive tracer agents and Re-188/186 radioactive treatment medicine; meanwhile, the application range of the HBED-CC derivatives as radiopharmaceutical marker precursors is also expanded.
- -
-
Paragraph 0071; 0073; 0074; 0075; 0076; 0077
(2019/04/02)
-
- A Convenient Synthesis for HBED-CC-tris(tert -butyl ester)
-
HBED-CC is a bifunctional complexing agent that, at ambient temperature, tightly chelates the trivalent radiometal 68 Ga (T 1/2 = 68 min). This complexing agent has attracted a lot of interest in tumor imaging applications. Depending on the chemical structure, different HBED-CC variants may be employed as radiolabeling precursor for the synthesis of desired radiopharmaceuticals. In this context, HBED-CC-tris(tert-butyl ester) is the only known monovalent variant of HBED-CC which is used for the synthesis of non-symmetric HBED-CC-based radiopharmaceuticals. Commercial HBED-CC-tris(tert -butyl ester) is very expensive, with limited availability. Nevertheless, no synthetic procedure for this useful product has been reported to date. This work introduces a convenient and comparatively cost-efficient method for the preparation of HBED-CC-tris(tert -butyl ester).
- Makarem, Ata,Konrad, Moritz,Liolios, Christos,Kopka, Klaus
-
p. 1239 - 1243
(2018/03/21)
-
- Synthetic process of esmolol intermediate 3-(4-hydroxyphenyl) methyl propionate
-
The invention belongs to the field of medicinal chemical industry, and particularly relates to a synthetic process of an esmolol intermediate 3-(4-hydroxyphenyl) methyl propionate. The synthetic process comprises the steps of: adopting p-methyl phenol and acetic anhydride as raw materials, performing an acylation reaction to obtain (4-methyl) phenol acetate, performing a halogenation reaction between the obtained (4-methyl) phenol acetate and a halogenating reagent, then carrying out a substitution reaction between the halogenated product and diethyl malonate, performing hydrolysis decarboxylation, and then carrying out an esterification reaction between the obtained product with methanol to obtain the 3-(4-hydroxyphenyl) methyl propionate. Through the route of the synthetic process, the process conditions are optimized, and the synthetic process has simple operation, easy and available raw materials and low cost; and the 3-(4-hydroxyphenyl) methyl propionate is obtained finally through acylation, halogenation, substitution, hydrolysis decarboxylation and the esterification reaction, and the synthetic process has a good industrial value and a total yield of 48.8%.
- -
-
Paragraph 0020; 0028; 0029; 0034
(2018/11/03)
-
- Method for synthesizing 1, 7-2-(4-hydroxy phenyl)-heptane-1, 4-diene-3-ketone
-
The invention relates to the field of pharmaceutical synthesis, in particular to a method for synthesizing 1,7-2-(4-hydroxy phenyl)-heptane-1,4-diene-3-ketone. The method, selecting 3-(4- hydroxy phenyl)propionic acid and 4-hydroxybenzaldehyde as raw materials, includes (1), subjecting the 3-(4-hydroxy phenyl)propionic acid to esterification, methyl protection, reduction and oxidation to obtain 3-(4-(methoxy methyl)phenyl)propionaldehyde; (2), subjecting the 4-hydroxybenzaldehyde to etherification and aldol reaction to obtain 4-(4-((methoxy methyl)phenyl)butyl-3-alkene-2-ketone; (3), subjecting the 4-(4-((methoxy methyl)phenyl) butyl-3-alkene-2-ketone and the 3-(4-(methoxy methyl)phenyl)propionaldehyde to aldol condensation, and allowing the reactor to react with hydrochloric acid to obtain 1, 7-2-(4-hydroxy phenyl)-heptane-1,4-diene-3-ketone. The method has the advantages of simplicity, easiness in operation, high yield and high purity.
- -
-
Paragraph 0043; 0044-0046
(2018/04/03)
-
- Modulating the selectivity of matriptase-2 inhibitors with unnatural amino acids
-
Matriptase-2, a type II transmembrane serine protease (TTSP), is expressed in the liver and regulates iron homeostasis via the cleavage of hemojuvelin. Matriptase-2 emerges as an attractive target for the treatment of conditions associated with iron overload, such as hemochromatosis or beta-thalassemia. Starting from the crystal structure of its closest homolog matriptase, we constructed a homology model of matriptase-2 in order to further optimize the selectivity of serine trap peptidomimetic inhibitors for matriptase-2 vs matriptase. Careful modifications of the P4, P3 and P2 positions with the help of unnatural amino acids led to a thorough understanding of Structure-Activity Relationship and a >60-fold increase in selectivity for matriptase-2 vs matriptase. Additionally, the introduction of unnatural amino acids led to significant increases in plasma stability. Such compounds represent useful pharmacological tools to test matriptase-2 inhibition in a context of iron overload.
- St-Georges, Catherine,Désilets, Antoine,Béliveau, Fran?ois,Ghinet, Mariana,Dion, Sébastien P.,Colombo, éloic,Boudreault, Pierre-Luc,Najmanovich, Rafael J.,Leduc, Richard,Marsault, éric
-
p. 110 - 123
(2017/02/23)
-
- Discovery of the First Environment-Sensitive Fluorescent Probe for GPR120 (FFA4) Imaging
-
GPR120, which is activated by long-chain free fatty acids (FFAs), has been recognized as a new attractive target for the treatment of type 2 diabetes and metabolic disease. The visualization and location of GPR120 in native cells can provide powerful information for guiding the physiological and pathological studies of GPR120. We report herein the first potent fluorescent probes that sensitively detect GPR120. We designed and synthesized a series of novel environment-sensitive probes with suitable fluorescence property, high biological activity on the GPR120, and acceptable cytotoxicity. These fluorescent probes targeting GPR120 are expected to expand the toolkit for further studies on GPR120.
- Liu, Jiaxiang,Tian, Chengsen,Jiang, Tianyu,Gao, Yuqi,Zhou, Yubin,Li, Minyong,Du, Lupei
-
supporting information
p. 428 - 432
(2017/04/21)
-
- UREA-BASED PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA) INHIBITORS FOR IMAGING AND THERAPY
-
The present invention relates to compounds according to Formula I and Formula IV. These compounds display very good binding affinities to the PSMA binding sites. They can be labeled with [68Ga]GaCl3 with high yields and excellent radiochemical purity. The present invention also relates to pharmaceutical compositions comprising a pharmaceutical acceptable carrier and a compound of Formula I or Formula IV, or a pharmaceutically acceptable salt thereof.
- -
-
Paragraph 0072
(2017/07/31)
-
- 3-tertiary butyl-4-hydroxyphenylpropionic acid preparation method
-
The invention relates to a 3-tertiary butyl-4-hydroxyphenylpropionic acid preparation method. The 3-tertiary butyl-4-hydroxyphenylpropionic acid preparation method solves the problems of poor reaction selectivity, low yield and serious environmental pollution in the existing preparation process of 3-tertiary butyl-4-hydroxyphenylpropionic acid. The 3-tertiary butyl-4-hydroxyphenylpropionic acid preparation method comprises the following steps: step one, carrying out dealkylation reaction; step two, carrying out selective hydrolyzation, extracting to obtain a water phase and an organic phase, and recycling a solvent from the organic phase to obtain an organic phase concentrate; step three, separating and purifying to obtain crude 3-tertiary butyl-4-hydroxyphenylpropionic acid; recrystallizing the 3-tertiary butyl-4-hydroxyphenylpropionic acid to obtain the pure 3-tertiary butyl-4-hydroxyphenylpropionic acid, and recycling the solvent from a recrystallized mother solution to obtain mother solution recovered materials for later use; and step four, using the organic phase concentrate obtained in the step two as dealkylation reaction raw materials, recycling and reacting. The products prepared by the method are white crystals and have the purity of up to above 98.5%; the total yield of the products reaches above 90%; and the preparation method is used for preparing the 3-tertiary butyl-4-hydroxyphenylpropionic acid.
- -
-
Paragraph 0064-0067
(2017/09/01)
-
- Cholic acid derivatives and their preparation method and medical application
-
The invention relates to the field of pharmaceutical chemistry and relates to cholic acid derivatives and their preparation method and medical application and particularly relates to cholic acid derivatives having the general formula (I), their preparation method, a pharmaceutical composition containing the compounds, medical application of the cholic acid derivatives, and medical application of the cholic acid derivatives as drugs for preventing or treating hyperlipidemia, obesity or type II diabetes.
- -
-
Paragraph 0089; 0090; 0091; 0095; 0096; 0097
(2017/07/21)
-
- Traceless and Chemoselective Amine Bioconjugation via Phthalimidine Formation in Native Protein Modification
-
ortho-Phthalaldehyde (OPA) and its derivatives are found to react chemoselectively with amino groups on peptides and proteins rapidly and tracelessly under the physiological condition via formation of phthalimidines, which provides a novel and promising approach when performing bioconjugation on native proteins. The notable advantages of this method over the existing native protein lysine-labeling approaches include a traceless process, a self-reacting, specific and fast reaction, ease of operation, and the ability to use nonhydrolyzable reagents. Its applications have been effectively demonstrated including conjugation of peptides and proteins, and generation of an active PEGlyated l-asparaginase.
- Tung, Chun Ling,Wong, Clarence T. T.,Fung, Eva Yi Man,Li, Xuechen
-
supporting information
p. 2600 - 2603
(2016/06/15)
-
- 68Ga-Bivalent Polypegylated Styrylpyridine Conjugates for Imaging Aβ Plaques in Cerebral Amyloid Angiopathy
-
Aβ plaques deposited on blood vessels are associated with cerebral amyloid angiopathy (CAA). In an effort to selectively map these Aβ plaques, we are reporting a new series of 68Ga labeled styrylpyridine derivatives with high molecular weights. In vitro binding to Aβ plaques in post-mortem Alzheimer's disease (AD) brain tissue showed that these 68Ga labeled bivalent styrylpyridines displayed good affinities and specificity (Ki 68Ga complexes to Aβ plaques. Biodistribution studies in normal mice showed very low initial brain uptakes (68Ga labeled bivalent styrylpyridines may be promising candidates as PET imaging radiotracers for detecting CAA.
- Zha, Zhihao,Song, Jin,Choi, Seok Rye,Wu, Zehui,Ploessl, Karl,Smith, Megan,Kung, Hank
-
p. 1314 - 1323
(2016/06/09)
-
- A butene liquid crystal compound and its preparation method
-
The invention relates to a butylene type liquid crystal compound and a preparation method of the same. Such compounds are novel negative liquid crystal materials with low viscosity and high absolute value of dielectric constant, have better chemical stability and better stability in light environment and high-temperature environment, and have very high application valve. The butylene type liquid crystal compound is structured as a structural formula shown in the specification, wherein in the structural formula of the compound, R1 refers to hydrogen atom, linear alkyl with 1-8 carbon atoms or linear alkenyl with 2-8 carbon atoms, or alkoxy or alkenyloxy formed by substituting one or two nonadjacent CH2 in the linear alkyl or the linear alkenyl with oxygen atoms, and 0-4 hydrogen atoms in the R1 group are substituted by fluorine; R2 refers to hydrogen atoms or linear alkyl with 1-8 carbon atoms, and 0-4 hydrogen atoms in the R2 group are substituted by fluorine; n = 1 to 2.
- -
-
Paragraph 0070; 0082; 0083
(2016/10/10)
-
- Palladium-Catalyzed Directed para C?H Functionalization of Phenols
-
Various practical methods for the selective C?H functionalization of the ortho and recently also of the meta position of an arene have already been developed. Following our recent development of the directing-group-assisted para C?H functionalization of toluene derivatives, we herein report the first remote para C?H functionalization of phenol derivatives by using a recyclable silicon-containing biphenyl-based template. The effectiveness of this strategy was illustrated with different synthetic elaborations and by the synthesis of various phenol-based natural products.
- Patra, Tuhin,Bag, Sukdev,Kancherla, Rajesh,Mondal, Anirban,Dey, Aniruddha,Pimparkar, Sandeep,Agasti, Soumitra,Modak, Atanu,Maiti, Debabrata
-
supporting information
p. 7751 - 7755
(2016/07/07)
-
- Carbon nanotubes supported tyrosinase in the synthesis of lipophilic hydroxytyrosol and dihydrocaffeoyl catechols with antiviral activity against DNA and RNA viruses
-
Hydroxytyrosol and dihydrocaffeoyl catechols with lipophilic properties have been synthesized in high yield using tyrosinase immobilized on multi-walled carbon nanotubes by the Layer-by-Layer technique. All synthesized catechols were evaluated against a large panel of DNA and RNA viruses, including Poliovirus type 1, Echovirus type 9, Herpes simplex virus type 1 (HSV-1), Herpes simplex virus type 2 (HSV-2), Coxsackievirus type B3 (Cox B3), Adenovirus type 2 and type 5 and Cytomegalovirus (CMV). A significant antiviral activity was observed in the inhibition of HSV-1, HSV-2, Cox B3 and CMV. The mechanism of action of the most active dihydrocaffeoyl derivative was investigated against a model of HSV-1 infection.
- Botta, Giorgia,Bizzarri, Bruno Mattia,Garozzo, Adriana,Timpanaro, Rossella,Bisignano, Benedetta,Amatore, Donatella,Palamara, Anna Teresa,Nencioni, Lucia,Saladino, Raffaele
-
supporting information
p. 5345 - 5351
(2015/11/11)
-
- COMPOUND EXHIBITING REGULATORY ACTIVITY ON LYSOPHOSPHATIDYLSERINE RECEPTOR FUNCTION
-
The object of the present invention is to provide a compound having a lysophosphatidylserine receptor function modulation activity or a salt thereof. A compound having a lysophosphatidylserine receptor function modulation activity or a salt thereof, or a pharmaceutical composition or a lysophosphatidylserine receptor function moderator containing such compound or salt is provided by the present invention.
- -
-
Paragraph 0217
(2015/12/19)
-
- Synthesis and evaluation of cationic norbornanes as peptidomimetic antibacterial agents
-
A series of structurally amphiphilic biscationic norbornanes have been synthesised as rigidified, low molecular weight peptidomimetics of cationic antimicrobial peptides. A variety of charged hydrophilic functionalities were attached to the norbornane scaffold including aminium, guanidinium, imidazolium and pyridinium moieties. Additionally, a range of hydrophobic groups of differing sizes were incorporated through an acetal linkage. The compounds were evaluated for antibacterial activity against both Gram-negative and Gram-positive bacteria. Activity was observed across the series; the most potent of which exhibited an MIC's ≤ 1 μg mL-1 against Streptococcus pneumoniae, Enterococcus faecalis and several strains of Staphylococcus aureus, including multi-resistant methicillin resistant (mMRSA), glycopeptide-intermediate (GISA) and vancomycin-intermediate (VISA) S. aureus.
- Hickey, Shane M.,Ashton, Trent D.,Khosa, Simren K.,Robson, Ryan N.,White, Jonathan M.,Li, Jian,Nation, Roger L.,Yu, Heidi Y.,Elliott, Alysha G.,Butler, Mark S.,Huang, Johnny X.,Cooper, Matthew A.,Pfeffer, Frederick M.
-
supporting information
p. 6225 - 6241
(2015/06/08)
-
- Catechol-based substrates of chalcone synthase as a scaffold for novel inhibitors of PqsD
-
A new strategy for treating Pseudomonas aeruginosa infections could be disrupting the Pseudomonas Quinolone Signal (PQS) quorum sensing (QS) system. The goal is to impair communication among the cells and, hence, reduce the expression of virulence factors and the formation of biofilms. PqsD is an essential enzyme for the synthesis of PQS and shares some features with chalcone synthase (CHS2), an enzyme expressed in Medicago sativa. Both proteins are quite similar concerning the size of the active site, the catalytic residues and the electrostatic surface potential at the entrance of the substrate tunnel. Hence, we evaluated selected substrates of the vegetable enzyme as potential inhibitors of the bacterial protein. This similarity-guided approach led to the identification of a new class of PqsD inhibitors having a catechol structure as an essential feature for activity, a saturated linker with two or more carbons and an ester moiety bearing bulky substituents. The developed compounds showed PqsD inhibition with IC50 values in the single-digit micromolar range. The binding mode of these compounds was investigated by Surface Plasmon Resonance (SPR) experiments revealing that their interaction with the protein is not influenced by the presence of the anthranilic acid bound to active site cysteine. Importantly, some compounds reduced the signal molecule production in cellulo.
- Allegretta, Giuseppe,Weidel, Elisabeth,Empting, Martin,Hartmann, Rolf W.
-
p. 351 - 359
(2015/02/19)
-
- Computational and Experimental Studies of Phthaloyl Peroxide-Mediated Hydroxylation of Arenes Yield a More Reactive Derivative, 4,5-Dichlorophthaloyl Peroxide
-
The oxidation of arenes by the reagent phthaloyl peroxide provides a new method for the synthesis of phenols. A new, more reactive arene oxidizing reagent, 4,5-dichlorophthaloyl peroxide, computationally predicted and experimentally determined to possess enhanced reactivity, has expanded the scope of the reaction while maintaining a high level of tolerance for diverse functional groups. The reaction proceeds through a novel "reverse-rebound" mechanism with diradical intermediates. Mechanistic insight was achieved through isolation and characterization of minor byproducts, determination of linear free energy correlations, and computational analysis of substituent effects of arenes, each of which provided additional support for the reaction proceeding through the diradical pathway.
- Camelio, Andrew M.,Liang, Yong,Eliasen, Anders M.,Johnson, Trevor C.,Yuan, Changxia,Schuppe, Alex W.,Houk,Siegel, Dionicio
-
p. 8084 - 8095
(2015/09/01)
-
- A recyclable CO surrogate in regioselective alkoxycarbonylation of alkenes: Indirect use of carbon dioxide
-
Herein, we report a Pd-catalysed alkoxycarbonylation of alkenes based on the use of a recyclable CO2 reduction product, the crystalline and air-stable N-formylsaccharin, as a CO surrogate. The carbonylation proceeds under ambient conditions in an exceptionally complementary regioselective fashion yielding the desired branched products from styrene derivatives and valuable linear esters from alkyl-substituted alkenes.
- Gehrtz,Hirschbeck,Fleischer
-
supporting information
p. 12574 - 12577
(2015/08/06)
-
- HYDROXY ALIPHATIC SUBSTITUTED PHENYL AMINOALKYL ETHER DERIVATIVES
-
New hydroxy aliphatic substituted phenyl aminoalkyl ether compounds of formula (I), compositions thereof and their use as a medicament in the treatment of nervous system diseases and/or the treatment of developmental, behavioral and/or mental disorders associated with cognitive deficits.
- -
-
-
- THIOARYL DERIVATIVES AS GPR120 AGONISTS
-
The present invention relates to thioaryl derivatives of Formula 1 as defined in the specification, a method for preparing the same, a pharmaceutical composition comprising the same and use thereof. The thioaryl derivatives of Formula 1 according to the present invention promote GLP-1 formation in the gastrointestinal tract and improve insulin resistance in macrophages, pancreas cells, etc. due to anti-inflammatory action, and can accordingly be effectively used for preventing or treating diabetes, complications of diabetes, inflammation, obesity, non-alcoholic fatty liver, steatohepatitis or osteoporosis.
- -
-
Paragraph 355-357
(2014/05/24)
-
- CYCLIC PEROXIDE OXIDATION OF AROMATIC COMPOUND PRODUCTION AND USE THEREOF
-
The present invention provides a method for converting an aromatic hydrocarbon to a phenol by providing an aromatic hydrocarbon comprising one or more aromatic C-H bonds and one or more activated C-H bonds in a solvent; adding a phthaloyl peroxide to the solvent; converting the phthaloyl peroxide to a di-radical; contacting the di-radical with the one or more aromatic C-H bonds; oxidizing selectively one of the one or more aromatic C-H bonds in preference to the one or more activated C-H bonds; adding a hydroxyl group to the one of the one or more aromatic C-H bonds to form one or more phenols; and purifying the one or more phenols.
- -
-
Page/Page column 10
(2014/10/15)
-
- Pd(II)-catalyzed intermolecular arylation of unactivated C(sp 3)-H bonds with aryl bromides enabled by 8-aminoquinoline auxiliary
-
An example of using readily available, less reactive aryl bromides as arylating reagents in the Pd(II)-catalyzed intermolecular arylation of unactivated C(sp3)-H bonds is described. This reaction was promoted by a crucial 8-aminoquinolinyl directing group and a K2CO3 base, enabling regiospecific installation of an aryl scaffold at the β-position of carboxamides. A mechanistic study by DFT calculations reveals a C(sp3)-H activation-led pathway featuring the oxidative addition as the highest energy transition state.
- Wei, Yu,Tang, Huarong,Cong, Xuefeng,Rao, Bin,Wu, Chao,Zeng, Xiaoming
-
supporting information
p. 2248 - 2251
(2014/05/06)
-
- Ti/Ni-mediated inter- and intramolecular conjugate addition of aryl and alkenyl halides and triflates
-
In this work, we show that the unique combination of a nickel catalyst and Cp2TiCl allows the direct conjugate addition of aryl and alkenyl iodides, bromides, and to a lesser extent, chlorides and triflates to α,β-unsaturated carbonyls at room temperature, without requiring the previous formation of an organometallic nucleophile. The reaction proceeds inter- and intramolecularly with good functional group compatibility, which is key for the development of free protecting group methodologies. Carbo- and heterocycles of five- and six-membered rings are obtained in good yields. Moreover, some insights about the mechanism involved have been obtained from cyclic voltammetry, UV-vis, and HRTEM measurements.
- Marquez, Irene R.,Miguel, Delia,Millan, Alba,Marcos, M. Luisa,De Cienfuegos, Luis Alvarez,Campana, Araceli G.,Cuerva, Juan M.
-
p. 1529 - 1541
(2014/03/21)
-
- Hydroxy aliphatic substituted phenyl aminoalkyl ether derivatives
-
New hydroxy aliphatic substituted phenyl aminoalkyl ether compounds of formula (1), compositions thereof and their use as a medicament in the treatment of nervous system diseases and/or the treatment of developmental, behavioral and/or mental disorders associated with cognitive deficits.
- -
-
-
- A biocompatible alkene hydrogenation merges organic synthesis with microbial metabolism
-
Organic chemists and metabolic engineers use orthogonal technologies to construct essential small molecules such as pharmaceuticals and commodity chemicals. While chemists have leveraged the unique capabilities of biological catalysts for small-molecule production, metabolic engineers have not likewise integrated reactions from organic synthesis with the metabolism of living organisms. Reported herein is a method for alkene hydrogenation which utilizes a palladium catalyst and hydrogen gas generated directly by a living microorganism. This biocompatible transformation, which requires both catalyst and microbe, and can be used on a preparative scale, represents a new strategy for chemical synthesis that combines organic chemistry and metabolic engineering. Reduction to practice: A hydrogenation reaction has been developed that employs hydrogen generated in situ by a microorganism and a biocompatible palladium catalyst to reduce alkenes on a synthetically useful scale. This type of transformation, which directly combines tools from organic chemistry with the metabolism of a living organism for small-molecule production, represents a new strategy for chemical synthesis.
- Sirasani, Gopal,Tong, Liuchuan,Balskus, Emily P.
-
p. 7785 - 7788
(2014/08/05)
-
- Asymmetric NHC-catalyzed redox α-amination of α- aroyloxyaldehydes
-
Asymmetric α-amination through an N-heterocyclic carbene (NHC)-catalyzed redox reaction of α-aroyloxyaldehydes with N-aryl-N-aroyldiazenes to form α-hydrazino esters with high enantioselectivity (up to 99% ee) is reported. The hydrazide products are readily converted into enantioenriched N-aryl amino esters through samarium(II) iodide mediated N-N bond cleavage.
- Taylor, James E.,Daniels, David S. B.,Smith, Andrew D.
-
supporting information
p. 6058 - 6061
(2014/01/06)
-
- A singlet oxygen approach to oxaspirocycles
-
A method for the preparation of oxygen containing spirocycles using singlet oxygen is reported. A series of phenols were converted into the corresponding peroxy-cyclohexadienone derivatives by irradiation with visible light in the presence of a sensitizer and oxygen. The resulting peroxides could be converted into ether and lactone spirocycles in one or two steps. The synthesis of the oxaspirocycles from the phenols can also be performed in a one-pot fashion, avoiding the isolation of the peroxide intermediates.
- Jones, Kevin M.,Hillringhaus, Tim,Klussmann, Martin
-
supporting information
p. 3294 - 3297
(2013/06/27)
-
- π-Conjugated polymer-Eu3+ complexes: Versatile luminescent molecular probes for temperature sensing
-
We report π-conjugated polymer-Eu3+ ion complexes as new potential luminescent thermo-sensitive molecular probes. Carboxylic acid functionalized segmented π-conjugated polymers having oligophenylenevinylene (OPV) chromophores in the poly(ethyleneoxide) or polymethylene backbones were custom designed, synthesized and utilized as efficient photosensitizers for Eu3+ ions. These π-conjugated polymer-Eu3+ ion complexes were found to be thermo-sensitive and behaved as reversible 'turn-on' or 'turn-off' luminescent switches in solution and in solid state. Luminescent decay studies revealed that the red-emission from the Eu3+ ion excited state was highly sensitive to temperature which drove the functioning of optical switches. The decay rate constants followed a typical Arrhenius trend over a wide temperature range having similar activation energies. Both the nature as well as length of the segmented polymer chain that tied the OPV optical chromophores in the backbone determine the temperature range of the luminescent on-off process. The emission characteristics of the oligomer-Eu 3+ ion complex were found to be non-thermosensitive which emphasized the need for the segmented π-conjugated polymer ligand structure for the probes based on Eu3+ ion complexes. The present strategy opens up new concept and molecular design principles for π-conjugated polymer-lanthanide ion complexes as potential candidates for temperature sensitive luminescent molecular probes. The Royal Society of Chemistry 2013.
- Balamurugan,Reddy,Jayakannan
-
p. 2256 - 2266
(2013/07/31)
-
- Tyrosinase and Layer-by-Layer supported tyrosinases in the synthesis of lipophilic catechols with antiinfluenza activity
-
Catechol derivatives with lipophilic properties have been selectively synthesized by tyrosinase in high yield avoiding long and tedious protection/deprotection steps usually required in traditional procedures. The synthesis was effective also with immobilized tyrosinase able to perform for more runs. The novel catechols were evaluated against influenza A virus, that continue to represent a severe threat worldwide. A significant antiviral activity was observed in derivatives characterized by antioxidant activity and long carbon alkyl side-chains, suggesting the possibility of a new inhibition mechanism based on both redox and lipophilic properties.
- Bozzini, Tiziana,Botta, Giorgia,Delfino, Michela,Onofri, Silvano,Saladino, Raffaele,Amatore, Donatella,Sgarbanti, Rossella,Nencioni, Lucia,Palamara, Anna Teresa
-
p. 7699 - 7708
(2014/01/06)
-
- NITRIC OXIDE DONOR NEPRILYSIN INHIBITORS
-
In one aspect, the invention relates to compounds having the formula: where R1, R2, R3, R7, R8, Z, X, b, and c are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds are nitric oxide donors and have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.
- -
-
Paragraph 0387; 0388
(2014/01/07)
-
- Design, synthesis, and evaluation of curcumin-derived arylheptanoids for glioblastoma and neuroblastoma cytotoxicity
-
Using an innovative approach toward multiple carbon-carbon bond-formations that relies on the multifaceted catalytic properties of titanocene complexes we constructed a series of C1-C7 analogs of curcumin for evaluation as brain and peripheral nervous system anti-cancer agents. C2-Arylated analogs proved efficacious against neuroblastoma (SK-N-SH & SK-N-FI) and glioblastoma multiforme (U87MG) cell lines. Similar inhibitory activity was also evident in p53 knockdown U87MG GBM cells. Furthermore, lead compounds showed limited growth inhibition in vitro against normal primary human CD34+hematopoietic progenitor cells. Taken together, the present findings indicate that these curcumin analogs are viable lead compounds for the development of new central and peripheral nervous system cancer chemotherapeutics with the potential for little effects on normal hematopoietic progenitor cells.
- Campos, Catherine A.,Gianino, Joseph B.,Bailey, Barbara J.,Baluyut, Mary E.,Wiek, Constanze,Hanenberg, Helmut,Shannon, Harlan E.,Pollok, Karen E.,Ashfeld, Brandon L.
-
supporting information
p. 6874 - 6878
(2014/01/06)
-
- Catalytic methyl transfer from dimethylcarbonate to carboxylic acids
-
Although methylation reactions are commonplace, currently used reagents are hazardous, toxic, and/or unstable. Dimethylcarbonate has been put forth as an inexpensive, nontoxic, and green potential methylating reagent. Herein we report a general, base-catalyzed methyl transfer from dimethylcarbonate to carboxylic acids. High selectivity for esterification is observed even in the presence of unprotected phenols, and the mild reaction conditions enable conservation of stereochemistry at epimerizable stereocenters. Isotope-labeling studies suggest a mechanism proceeding by direct methyl transfer from dimethylcarbonate to the substrate.
- Ji, Yuan,Sweeney, Jessica,Zoglio, Jillian,Gorin, David J.
-
p. 11606 - 11611
(2013/12/04)
-
- Renewable benzoxazine monomers from Lignin-like naturally occurring phenolic derivatives
-
The benzoxazines of three naturally occurring phenylpropanoid phenols: ferulic, coumaric, and phloretic acids, and their esters are described. Benzoxazines with conjugated unsaturated chains exhibit unusual poor thermal stability and degrade partially at the polymerization temperature making necessary the use of a catalyst (BF3.Et2O) to low the polymerization temperature and prevent degradation. Polybenzoxazines are prepared thermally and characterized by DSC and TGA techniques. The resulting materials have superior Tgs when compared with those prepared from an unsubstituted monofuctional benzoxazine due to the additional crosslinking through the ester and carboxylic moieties.
- Comí, Marc,Lligadas, Gerard,Ronda, Juan C.,Galià, Marina,Cádiz, Virginia
-
p. 4894 - 4903
(2013/11/06)
-
- Hitting a soft drug with a hard nucleophile: Preparation of esmolol's metabolite by treatment with bis(tributyltin) oxide
-
A facile method for the production of esmolol's metabolite in high purity is described. Bis(tributyltin) oxide is used to disrupt esmolol's ester linkage, and hydrolysis is completed by addition of water, which also allows the inorganic side products to be conveniently extracted into ether. Evaporation of the aqueous phase and trituration with ethyl acetate provides the carboxylic acid-amine internal salt as a white, free-flowing powder. Taylor & Francis Group, LLC.
- Zhang, Cunyu A.,Erhardt, Paul W.
-
scheme or table
p. 722 - 726
(2012/01/13)
-
- AGONISTS OF GPR40
-
The present invention relates to compounds that have the ability to modulate the activity of GPR40 and are there-fore useful in the treatment of GPR40 related disorders. In addition the invention relates to the compounds, methods for their preparation, pharmaceutical compositions containing the compounds and the uses of these compounds in the treatment of certain disorders related to GPR40 activity.
- -
-
Page/Page column 59; 60
(2012/02/05)
-
- A simple and straightforward approach toward selective C=C bond reduction by hydrazine
-
A simple and straightforward method for reducing the C=C double bond with hydrazine is described. A number of representative C=C bonds in various steric and electronic environments were examined. Substituted alkenes can be selectively reduced in EtOH in the presence of hydrazine to give the corresponding products in up to 100% yields.
- Chen, Hao,Wang, Jianmin,Hong, Xuechuan,Zhou, Hai-Bing,Dong, Chune
-
supporting information
p. 758 - 761
(2012/11/07)
-