- New calcium-selective smart contrast agents for magnetic resonance imaging
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Calcium plays a vital role in the human body and especially in the central nervous system. Precise maintenance of Ca2+ levels is very crucial for normal cell physiology and health. The deregulation of calcium homeostasis can lead to neuronal cell death and brain damage. To study this functional role played by Ca2+ in the brain noninvasively by using magnetic resonance imaging, we have synthesized a new set of Ca2+-sensitive smart contrast agents (CAs). The agents were found to be highly selective to Ca 2+ in the presence of other competitive anions and cations in buffer and in physiological fluids. The structure of CAs comprises Gd3+-DO3A (DO3A=1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane) coupled to a Ca2+ chelator o-amino phenol-N,N,O-triacetate (APTRA). The agents are designed to sense Ca2+ present in extracellular fluid of the brain where its concentration is relatively high, that is, 1.2-0.8 mM. The determined dissociation constant of the CAs to Ca2+ falls in the range required to sense and report changes in extracellular Ca2+ levels followed by an increase in neural activity. In buffer, with the addition of Ca2+ the increase in relaxivity ranged from 100-157 %, the highest ever known for any T1-based Ca2+-sensitive smart CA. The CAs were analyzed extensively by the measurement of luminescence lifetime measurement on Tb 3+ analogues, nuclear magnetic relaxation dispersion (NMRD), and 17O NMR transverse relaxation and shift experiments. The results obtained confirmed that the large relaxivity enhancement observed upon Ca 2+ addition is due to the increase of the hydration state of the complexes together with the slowing down of the molecular rotation and the retention of a significant contribution of the water molecules of the second sphere of hydration. Smart Ca2+ sensing in the brain: To study Ca2+ in the brain noninvasively by magnetic resonance imaging, a new set of Ca2+-sensitive smart contrast agents (CAs) have been synthesized. The agents were found to be highly selective to Ca2+ in the presence of other competitive anions and cations in buffer and in physiological fluids. The determined dissociation constant of the CAs to Ca 2+ falls in the range required to sense and report changes in extracellular Ca2+ levels in response to neural activity (see figure). Copyright
- Verma, Kirti Dhingra,Forgacs, Attila,Uh, Hyounsoo,Beyerlein, Michael,Maier, Martin E.,Petoud, Stephane,Botta, Mauro,Logothetis, Nikos K.
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- Low toxicity functionalised imidazolium salts for task specific ionic liquid electrolytes in dye-sensitised solar cells: A step towards less hazardous energy production
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Novel solvent free task specific ionic liquid (TSIL) electrolytes for dye sensitised solar cells (DSSC) were synthesised and tested. Of great concern is the replacement of low-moderate toxicity second generation ILs, with high toxicity third generation TSILs. As most 1-butyl-3-methylimidazolium (Bmim) and especially 1-ethyl-3-methylimidazolium (Emim) based ILs have low toxicity, the designing of replacement TSILs of comparable toxicity is a challenge. Structural features of TSIL investigated herein were incorporation of heteroatoms into the side chain of imidazolium cations (i.e. ether, ester and amide) and anion (bromide, iodide, and triflimide [NTf2]). Preliminary toxicity screening against 20 microorganisms (8 bacteria and 12 fungi) found that all ILs, imidazolium salts, N-butylbenzimidazole (NBB) and guanidinium thiocyanate (GNCS) do not exhibit high antimicrobial toxicity. However NBB and a pentyl ester substituted IL displayed moderate toxicity to several strains of bacteria and fungi. Further toxicity testing to establish IC50 values shows several novel TSIL compounds and imidazolium salts are in fact less toxic to microorganisms (e.g. bacteria) than commonly used 1-ethyl-3-methylimidazolium iodide (EmimI) and 1,3-dimethylimidazolium iodide (DmimI). We have demonstrated that the presence of ether and either ester or amide groups in the structure of the cation of the TSIL and imidazolium salts reduces antimicrobial toxicity, which is consistent with the lowering of the lipophilicity of ILs. Iodide and bromide analogues have lower toxicity than the NTf2 examples in this study. The DSSC performance using these "greener" ILs in place of the standard EmimI compare quite favourably. Two low antibacterial toxicity iodide examples exhibit photocurrents of 9.27 mA cm-2 and 8.85 mA cm -2, respectively, achieving promising efficiencies of 3.39% and 3.31%, respectively (EmimI = 4.94%). DSSC performance is further improved by 15% minimum to 66% maximum, depending on IL chosen, by the presence of small amounts of moisture and DSSCs employing a low antibacterial toxicity iodide TSIL or imidazolium salt can surpass the performance of dry EmimI. Of note the DSSC containing TSIL NTf2 examples, performed poorly compared to the halide analogues, with the outcome that the most toxic TSILs under investigation are also the least preferred based on performance. the Partner Organisations 2014.
- Ghavre, Mukund,Byrne, Owen,Altes, Lena,Surolia, Praveen K.,Spulak, Marcel,Quilty, Brid,Thampi, K. Ravindranathan,Gathergood, Nicholas
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- Exploring packing features of N-substituted acridone derivatives: Synthesis and X-ray crystallography studies
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The title compounds include an acridone as a parent molecule in which nitrogen is linked to other nitrogen-containing heterocyclic molecules through two carbon chain alkyl linkers connected by a C—N single bond. These acridone derivatives crystallized as Triclinic, Monoclinic, Tetragonal, and Orthorhombic having space group P1, P21/c, I41/a, Pca21, respectively at T = 273 K. In the present work, synthesis and single-crystal X-ray crystallographic study of four novel acridone derivatives are reported from the perspective of crystal engineering. This work is based on the comprehensive analysis of Hirshfeld surfaces, 2D fingerprint plots, and DFT studies. The single-crystal structure analysis showed that compounds are connected by various intermolecular interactions such as C – H?O, C – H?C/π, and π?π (C?C) stacking interactions, which are accountable for the arrangement and amplification of molecular assembly. The DFT studies using the B3LYP functional with the 6-311++ G (d,p) basis set are employed to compare the experimental results with theoretically obtained molecular parameters. The HOMO and LUMO analyzes were used to elucidate information regarding molecular reactivity and charge transfer within the molecule.
- Hussain, Javeena,Sahrawat, Parul,Dubey, Pankaj,Kirubakaran, Sivapriya,Thiruvenkatam, Vijay
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- Benzofuran substituted amide compound as well as preparation method and application thereof
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The invention relates to a benzofuran substituted amide compound as well as a preparation method and application thereof. The chemical structural general formula of the benzofuran substituted amide compound is represented by a formula VII. The invention discloses the structural general formula, a synthetic route and a preparation method of the benzofuran substituted amide compound, an application of the benzofuran substituted amide compound in a pesticide composition and an application of the benzofuran substituted amide compound in prevention and treatment of plant diseases in agriculture, forestry and horticulture when the benzofuran substituted amide compound is combined with a bactericide.
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Paragraph 0063-0066
(2021/06/12)
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- Biomimetic synthesis and anti-inflammatory evaluation of violacin A analogues
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Violacin A, a chromanone derivative, isolated from a fermentation broth of Streptomyces violaceoruber, has excellent anti-inflammatory potential. Herein, a biogenetically modeled approach to synthesize violacin A and twenty-five analogues was described, which involved the preparation of aromatic polyketide precursor through Claisen condensation and its spontaneous cyclization. The inhibitory effect on nitric oxide (NO) production of all synthetic molecules was evaluated by lipopolysaccharide (LPS)-induced Raw264.7 cells. The results revealed that introduction of aliphatic amine moieties on C-7 obviously improved the anti-inflammation effect of violacin A, and also the aromatic ether instead of ketone group at side chain was favorable to increase the activity. Among them, analogue 7a and 16d were screened as the most effective anti-inflammatory candidates. Molecular mechanism research revealed that 7a and 16d acquired anti-inflammatory ability due to the inhibition of NF-κB signaling pathway.
- Wu, Wenxi,Mu, Yu,Liu, Bo,Wang, Zixuan,Guan, Peipei,Han, Li,Jiang, Mingguo,Huang, Xueshi
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- Development of Selective Steroid Inhibitors for the Glucose-6-phosphate Dehydrogenase from Trypanosoma cruzi
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Chagas disease is a parasitic infection affecting millions of people across Latin America, imposing a dramatic socioeconomic burden. Despite the availability of drugs, nifurtimox and benznidazole, lack of efficacy and incidence of side-effects prompt the identification of novel, efficient, and affordable drug candidates. To address this issue, one strategy could be probing the susceptibility of Trypanosoma parasites toward NADP-dependent enzyme inhibitors. Recently, steroids of the androstane group have been described as highly potent but nonselective inhibitors of parasitic glucose-6-phosphate dehydrogenase (G6PDH). In order to promote selectivity, we have synthesized and evaluated 26 steroid derivatives of epiandrosterone in enzymatic assays, whereby 17 compounds were shown to display moderate to high selectivity for T. cruzi over the human G6PDH. In addition, three compounds were effective in killing intracellular T. cruzi forms infecting rat cardiomyocytes. Altogether, this study provides new SAR data around G6PDH and further supports this target for treating Chagas disease.
- Fredo Naciuk, Fabrício,Do Nascimento Faria, Jéssica,Gonc?lves Eufrásio, Amanda,Torres Cordeiro, Artur,Bruder, Marjorie
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supporting information
p. 1250 - 1256
(2020/07/27)
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- Synthesis, anticancer, and computational studies of 1, 3, 4-oxadiazole-purine derivatives
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Theophylline-7-acetic acid (acefylline) (3) and its derivatives are pharmacologically active compounds and generally recognized as bronchodilators for the treatment of respiratory diseases like acute asthma for over 70 years. In this article, synthesis of
- Faisal, Shahla,Kamal, Shagufta,Parveen, Bushra,Rasool, Nasir,Rasul, Azhar,Raza, Zohaib,Shahzadi, Irum,Zahid, Faisal M.,Zahoor, Ameer F.,Zia-ur-Rehman, Muhammad
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p. 2782 - 2794
(2020/04/16)
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- Synthesis and characterization of a new class of phenothiazine molecules with 10H-substituted morpholine & piperidine derivatives: A structural insight
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A series of 10H-substituted phenothiazine-based molecules were prepared by the base-catalyzed reactions. The synthesized compounds are characterized by Mass spectroscopy, NMR, and SCXRD to examine the role of different functional groups involved in the intermolecular interactions and conformational geometries. The crystal packing of the compounds is governed by O–H?O, C–H?O, and π–π interactions. A complete understanding of the intermolecular interactions is studied employing the Hirshfeld analysis, 2D Fingerprint plot. Furthermore, the density functional theory (DFT/B3LYP) method at the 6–311++G(d,p) basis set was performed to support and compare experimental & theoretical geometrical parameters of phenothiazine derivatives.
- Angira, Deekshi,Dubey, Pankaj,Hans, Tanya,Hussain, Javeena,Kirubakaran, Sivapriya,Thiruvenkatam, Vijay
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- Usnic Acid Enaminone-Coupled 1,2,3-Triazoles as Antibacterial and Antitubercular Agents
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(+)-Usnic acid, a product of secondary metabolism in lichens, has displayed a broad range of biological properties such as antitumor, antimicrobial, antiviral, anti-inflammatory, and insecticidal activities. Interested by these pharmacological activities and to tap into its potential, we herein present the synthesis and biological evaluation of new usnic acid enaminone-conjugated 1,2,3-triazoles 10-44 as antimycobacterial agents. (+)-Usnic acid was condensed with propargyl amine to give usnic acid enaminone 8 with a terminal ethynyl moiety. It was further reacted with various azides A1-A35 under copper catalysis to give triazoles 10-44 in good yields. Among the synthesized compounds, saccharin derivative 36 proved to be the most active analogue, inhibiting Mycobacterium tuberculosis (Mtb) at an MIC value of 2.5 μM. Analogues 16 and 27, with 3,4-difluorophenacyl and 2-acylnaphthalene units, respectively, inhibited Mtb at MIC values of 5.4 and 5.3 μM, respectively. Among the tested Gram-positive and Gram-negative bacteria, the new derivatives were active on Bacillus subtilis, with compounds 18 [3-(trifluoromethyl)phenacyl] and 29 (N-acylmorpholinyl) showing inhibitory concentrations of 41 and 90.7 μM, respectively, while they were inactive on the other tested bacterial strains. Overall, the study presented here is useful for converting natural (+)-usnic acid into antitubercular and antibacterial agents via incorporation of enaminone and 1,2,3-triazole functionalities.
- Bangalore, Pavan K.,Vagolu, Siva K.,Bollikanda, Rakesh K.,Veeragoni, Dileep K.,Choudante, Pallavi C.,Misra, Sunil,Sriram, Dharmarajan,Sridhar, Balasubramanian,Kantevari, Srinivas
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supporting information
p. 26 - 35
(2020/01/03)
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- NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF FIBROSIS
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The present invention discloses compounds according to Formula (I) Wherein R1, R2, L, A1, A2, A3, Cy and the subscript n are as defined herein. The present invention relates to antagonists compounds of sphingosine 1-phosphate (SIP) receptor, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases, inflammatory diseases, respiratory diseases, autoimmune diseases, metabolic diseases, cardiovascular diseases, and/or proliferative diseases by administering the compound of the invention.
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Paragraph 0255
(2019/01/21)
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- Design, Synthesis, Antimicrobial Evaluation, and Laccase Catalysis Effect of Novel Benzofuran–Oxadiazole and Benzofuran–Triazole Hybrids
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Novel structural hybrids of benzofuran–oxadiazole and benzofuran–triazole have been synthesized and evaluated for their potential against Staphylococcus aureus, Bacillus subtilis, and Escherichia coli. The excellent antibiotic activity was shown by compou
- Faiz, Sadia,Zahoor, Ameer Fawad,Ajmal, Muhammad,Kamal, Shagufta,Ahmad, Sajjad,Abdelgawad, Abdelrahman M.,Elnaggar, Mehrez E.
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p. 2839 - 2852
(2019/11/03)
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- Imidazo ring PAR4 antagonist and medical applications thereof
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The invention relates to an imidazo ring compound represented by formula (I) or formula (II), or a pharmaceutically acceptable salt or ester or solvate thereof. The compound disclosed by the inventioncan be used for preparing medicines for preventing or treating thromboembolic diseases.
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Paragraph 0755-0758
(2020/01/12)
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- Enantioselective Spirocyclopropanation of para-Quinone Methides Using Ammonium Ylides
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The use of Cinchona alkaloid-based chiral ammonium ylides allows for the first highly enantioselective and broadly applicable spirocyclopropanation reactions of para-quinone methides. This strategy provides a straightforward protocol toward the chiral spiro[2.5]octa-4,7-dien-6-one skeleton, which is a frequently found structural motif in important biologically active molecules.
- Roiser, Lukas,Waser, Mario
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supporting information
p. 2338 - 2341
(2017/05/12)
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- Modulators of ROR-gamma Receptors, Composition and Use Thereof
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The present invention provides novel methods to treat disease by modulating retinoid-related orphan receptor gamma (ROR-gamma) in vitro and in vivo with ursolic acid analogs, and compositions thereof. The methods and compounds disclosed herein are useful for inhibiting the differentiation of a population of T cells, or treating a disease related to Th17 cell responses in a subject. Examples of such diseases include, but are not limited to, autoimmune diseases, multiple sclerosis, rheumatoid arthritis, psoriasis and diabetes.
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Paragraph 0141; 0142
(2017/11/07)
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- Design, synthesis, and biological evaluation of chrysin derivatives as potential FabH inhibitors
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New series of chrysin derivatives (4a–4t) were designed and synthesized by introducing different substituted piperazines at C-7 position. Their inhibitory effects on FabH were evaluated using two Gram-negative bacterial strains, Escherichia coli and Pseudomonas aeruginosa, and two Gram-positive bacterial strains, Bacillus subtilis and Staphylococcus aureus. To our delight, most of these compounds exhibited a dramatic increase in inhibitory potency, compared with the control positive drugs. Among them, compound 4s exhibited the most potent inhibitory activity with IC50 values of 5.78?±?0.24?μm inhibiting E.?coli FabH and potent antibacterial activity against S.?aureus and E.?coli with MIC of 1.25?±?0.01, 1.15?±?0.12?μg/mL, respectively, comparing to the control positive drugs penicillin G (7.56?±?0.30?μm). Docking simulation was performed to position compound 4s into the FabH active site, and the result showed that compound 4s could bind well with the FabH as potent FabH inhibitor.
- Li, Hong-Xia,Wang, Zhong-Chang,Qian, Yu-Mei,Yan, Xiao-Qiang,Lu, Ya-Dong,Zhu, Hai-Liang
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p. 136 - 140
(2016/12/16)
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- On-resin N-terminal peptoid degradation: Toward mild sequencing conditions
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A novel approach to sequentially degrade peptoid N-terminal N-(substituted)glycine residues on the solid-phase using very mild conditions is reported. This method relies on the treatment of resin-bound, bromoacetylated peptoids with silver perchlorate in THF, leading to an intramolecular cyclization reaction to liberate the terminal residue as a N-substituted morpholine-2,5-dione, resulting in a truncated peptoid upon hydrolysis and a silver bromide byproduct. Side-chain functional group tolerance is explored and reaction kinetics are determined. In a series of pentapeptoids possessing variable, non-nucleophilic side-chains at the second position (R2), we demonstrate that sequential N-terminal degradation of the first two residues proceeds in 87% and 74% conversions on average, respectively. We further demonstrate that the degradation reaction is selective for peptoids, and represents substantial progress toward a mild, iterative sequencing method for peptoid oligomers.
- Proulx, Caroline,No?, Falko,Yoo, Stan,Connolly, Michael D.,Zuckermann, Ronald N.
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p. 726 - 736
(2017/02/14)
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- PREPARATION OF TICAGRELOR
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The present application relate to processes for preparing Ticagrelor and to intermediates that are useful in the processes.
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Page/Page column 23
(2016/01/25)
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- Synthesis of α-Functionalized Trichloromethylcarbinols
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A new series of α-functionalized trichloromethylcarbinols have been synthesized from corresponding α-halomethyl ketones, esters, and amides in 48-78% overall yields. Reactivity of nitrates obtained in the first step was dependent on the electron-withdrawi
- Ram, Ram N.,Soni, Vineet Kumar
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p. 8922 - 8928
(2015/09/15)
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- Synthesis of triazole-functionalized 2-DOS analogues and their evaluation as A-site binders
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Aminoglycoside-antibiotics represent important tools for studying the biological functions of RNA. An orthogonal protection strategy applied on 2-deoxystreptamine (2-DOS) revealed a series of key intermediates that enable its regioselective functionalization. Our approach allowed the construction of selected representatives of triazole-containing analogues with diverse molecular frameworks for biological evaluation regarding their binding and antibacterial potencies.
- Anastasopoulou, Panoula,Kythreoti, Georgia,Cosmidis, Tilemachos,Pyrkotis, Constantina,Nahmias, Victoria R.,Vourloumis, Dionisios
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supporting information
p. 1122 - 1126
(2014/03/21)
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- INHIBITING NEUROTRANSMITTER REUPTAKE
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This document relates to compounds as well as methods and materials involved in modulating neurotransmitter reuptake. For example, compounds, methods for synthesizing compounds, and methods for inhibiting neurotransmitter reuptake are provided.
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Page/Page column 132
(2014/10/15)
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- α-Bromodiazoacetamides - a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C-H insertion reactions
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In this work, we introduce a new class of halodiazocarbonyl compounds, α-halodiazoacetamides, which through a metal-free, ambient-temperature thermolysis perform intramolecular C-H insertions to produce α-halo-β-lactams. When carried out with α-bromodiazoacetamides bearing cyclic side chains, the thermolysis reaction affords bicyclic α-halo-β-lactams, in some cases in excellent yields, depending on the ring size and substitution pattern of the cyclic amide side chains.
- Kaupang, Asmund,Bonge-Hansen, Tore
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supporting information
p. 1407 - 1413
(2013/08/23)
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- Synthesis of berberine bromide analogs containing tertiary amides of acetic acid in the 9-O-position
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9-O-Acetamide analogs of berberine bromide were prepared in 20-87% yields via reaction of the isoquinoline alkaloid berberrubine with tertiary amides of bromoacetic acid. Aminolysis did not occur during reaction of methyl-2-(9-demethoxyberberine bromide-9-yl)hydroxyacetate with secondary amines. The corresponding acid or its ethyl ester was isolated.
- Nechepurenko,Komarova,Vasil'ev,Salakhutdinov
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p. 1047 - 1053
(2013/04/23)
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- Tandem ionic liquid antimicrobial toxicity and asymmetric catalysis study: Carbonyl-ene reactions with trifluoropyruvate
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The asymmetric carbonyl-ene reaction of trifluoropyruvate with five alkenes catalysed by [Pd{(R)-BINAP}](SbF6)2 were carried out in good yields and enantioselectivities (up to 96% yield and 96% ee) in low antimicrobial toxicity C2-substituted imidazolium ionic liquids (ILs). Toxicity data was included in the selection criteria for reaction optimisation after a preliminary IL screen. The Pd(ii) catalyst immobilised in an IL was recycled and reused up to 7 times without decrease of either yield or ee. One IL prepared, which was determined to be of high antimicrobial toxicity was assigned a low priority for future applications.
- Gore, Rohitkumar G.,Truong, Thi-Kim-Thu,Pour, Milan,Myles, Lauren,Connon, Stephen J.,Gathergood, Nicholas
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p. 2727 - 2739
(2013/10/08)
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- Isoxazolodihydropyridinones: 1,3-dipolar cycloaddition of nitrile oxides onto 2,4-dioxopiperidines
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Practical and efficient methods have been developed for the diversity-oriented synthesis of isoxazolodihydropyridinones via the 1,3-dipolar cycloaddition of nitrile oxides onto 2,4-dioxopiperidines. A select few of these isoxazolodihydropyridinones were further elaborated with triazoles by copper-catalyzed azide-alkyne cycloaddition reactions. A total of 70 compounds and intermediates were synthesized and analyzed for drug likeness. Sixty-four of these novel compounds were submitted to the NIH Molecular Libraries Small Molecule Repository for high-throughput biological screening.
- Coffman, Keith C.,Hartley, Timothy P.,Dallas, Jerry L.,Kurth, Mark J.
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body text
p. 280 - 284
(2012/05/19)
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- A formal method for the de-N,N-dialkylation of Sommelet-Hauser rearrangement products
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Selective amine de-alkylation enables the conversion of Sommelet-Hauser rearrangement products into 2-aryl-2-bromoacetic acid derivatives. These compounds are valuable synthetic intermediates in the synthesis of α-aryl-α-amino or α-aryl-β-amino acid deriv
- Tayama, Eiji,Sato, Ryota,Takedachi, Keisuke,Iwamoto, Hajime,Hasegawa, Eietsu
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supporting information; experimental part
p. 4710 - 4718
(2012/07/28)
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- Stereoselective synthesis of ambiphilic alkenes via regioselective methylation of α-trifluoromethanesulfonyl carbonyl compounds with trimethylsilyldiazomethane
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α-Trifluoromethanesulfonyl esters, ketones and amides are C-H acids capable of reacting with trimethylsilyldiazomethane to afford the corresponding ambiphilic alkenes. While esters were found to be non-selective, ketones were highly regioselective for O-methylation and displayed variable E/Z stereoselectivity. Amides were observed to be both highly regio- and stereoselective, affording O-methylation with exclusive formation of the Z-alkene.
- Kong, Han Il,Crichton, Jennifer E.,Manthorpe, Jeffrey M.
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supporting information; experimental part
p. 3714 - 3717
(2011/08/06)
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- The Davis-Beirut reaction: N 1, N 2-disubstituted-1 H-indazolones via 1,6-electrophilic addition to 3-alkoxy-2 H-indazoles
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A variety of electrophiles (anhydrides, acid chlorides, carbonochloridates, sulfonyl chlorides, and alkyl bromides) react with 3-methoxy-2H-indazole (1a), benzoxazin[3,2-b]indazole (1d), and oxazolino[3,2-b]indazole (1e) - substrates available by the Davi
- Conrad, Wayne E.,Fukazawa, Ryo,Haddadin, Makhluf J.,Kurth, Mark J.
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supporting information; experimental part
p. 3138 - 3141
(2011/07/31)
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- Bis(2-t-butylphenyl)phosphonoacetamides for the highly cis-selective synthesis of α,β-unsaturated amides
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New Horner-Wadsworth-Emmons reagents, (o-t-BuPhO)2P(O)CH2CONMe(OMe) and (o-t-BuPhO)2P(O)CH2CON(CH2CH2) 2O were prepared via the Arbuzov reaction in good yields. The HWE reaction
- Ando, Kaori,Nagaya, Shigeo,Tarumi, Yuko
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scheme or table
p. 5689 - 5691
(2011/02/26)
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- Stereoseleetive synthesis of polysubstituted alkenes through a phosphine-mediated three-component system of aldehydes, α-halo carbonyl compounds, and terminal alkenes
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A study was conducted to demonstrate stereoselective synthesis of polysubstituted alkenes through a phosphine-mediated three-component system of aldehydes, α-halo carbonyl compounds, and terminal alkenes. Triphenylphosphine, α-halo carbonyl compounds, and methyl acrylate were added to a solution of aldehyde in chloroform or 1-propanol under nitrogen at room temperature. The resulting mixture was stirred at the specified temperature until transformation was completely observed by thin layer chromatography (TLC) analysis. The mixture was cooled to room temperature and purified by column chromatography on silica gel, eluting with petroleum ether/ethyl acetate. The study demonstrated that the first one-pot and three-component reaction of aldehydes, α-haloacetates, and terminal alkenes was developed in the presence of phenylphosphine to produce a wide range of trisubstituted alkenes with significant stereoselectivity.
- Liu, Da-Neng,Tian, Shi-Kai
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supporting information; experimental part
p. 4538 - 4542
(2009/12/25)
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- Original TDAE strategy using α-halocarbonyl derivatives
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We report herein the selective C-C bond formation by the reaction of nitrobenzyl carbanions, formed via the TDAE strategy, with α-haloesters and α-haloamides. This reaction, extended in benzodioxole and dimethoxybenzene series provides new potentially CNS
- Since, Marc,Terme, Thierry,Vanelle, Patrice
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body text
p. 6128 - 6134
(2011/03/19)
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- Inhibition Of Raf Kinase Using Symmetrical And Unsymmetrical Substituted Diphenyl Ureas
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This invention relates to the use of a group of aryl ureas in treating raf mediated diseases, and pharmaceutical compositions for use in such therapy.
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Page/Page column 12
(2008/12/04)
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- Identification of a novel class of succinyl-nitrile-based Cathepsin S inhibitors
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The synthesis and in vitro activities of a series of succinyl-nitrile-based inhibitors of Cathepsin S are described. Several members of this class show nanomolar inhibition of the target enzyme as well as cellular potency. The inhibitors displaying the greatest potency contain N-alkyl substituted piperidine and pyrrolidine rings spiro-fused to the α-carbon of the P1 residue.
- Bekkali, Younes,Thomson, David S.,Betageri, Raj,Emmanuel, Michel J.,Hao, Ming-Hong,Hickey, Eugene,Liu, Weimin,Patel, Usha,Ward, Yancey D.,Young, Erick R.R.,Nelson, Richard,Kukulka, Alison,Brown, Maryanne L.,Crane, Kathy,White, Della,Freeman, Dorothy M.,Labadia, Mark E.,Wildeson, Jessi,Spero, Denice M.
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p. 2465 - 2469
(2008/03/11)
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- Synthesis and biological evaluations of sulfanyltriazoles as novel HIV-1 non-nucleoside reverse transcriptase inhibitors
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A novel sulfanyltriazole was discovered as an HIV-1 non-nucleoside reverse transcriptase inhibitor via HTS using a cell-based assay. Chemical modifications and molecular modeling studies were carried out to establish its SAR and understand its interactions with the enzyme. These modifications led to the identification of sulfanyltriazoles with low nanomolar potency for inhibiting HIV-1 replication and promising activities against selected NNRTI resistant mutants. These novel and potent sulfanyltriazoles could serve as advanced leads for further optimization.
- Wang, Zhiwei,Wu, Baogen,Kuhen, Kelli L.,Bursulaya, Badry,Nguyen, Truc N.,Nguyen, Deborah G.,He, Yun
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p. 4174 - 4177
(2007/10/03)
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- ALKYLOXY SUBSTITUTED THIAZOLOQUINOLINES AND THIAZOLONAPHTHYRIDINES
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Thiazoloquinolines and thiazolonaphthyridines with an alkoxy substituent at the 6, 7, 8, or 9-position, pharmaceutical compositions containing the compounds, intermediates, methods of making and methods of use of these compounds as immunomodulators, for inducing cytokine biosynthesis in animals and in the treatment of diseases including viral and neoplastic diseases are disclosed.
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Page/Page column 93-94
(2008/06/13)
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- SUBSTITUTED FUSED [1,2]IMIDAZO[4,5-C] RING COMPOUNDS AND METHODS
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Fused [1,2]imidazo[4,5-c] ring compounds, e.g., fused [1,2]imidazo[4,5-c]quinolines and [1,2]imidazo[4,5-c]naphthyridines, with a substituent, e.g., a substituted alkoxy substituent, at the 6, 7, 8, or 9-position, pharmaceutical compositions containing th
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Page/Page column 65
(2008/06/13)
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- INHIBITION OF p38 KINASE USING SYMMETRICAL AND UNSYMMETRICAL DIPHENYL UREAS
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This invention relates to the use of a group of aryl ureas in treating cytokine mediated diseases and proteolytic enzyme mediated diseases, and pharmaceutical compositions for use in such therapy.
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Page/Page column 24-25
(2010/02/11)
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- ALKOXY SUBSTITUTED IMIDAZOQUINOLINES
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Imidazoquinoline compounds with an alkoxy substituent at the 6, 7, 8, or 9-position, pharmaceutical compositions containing the compounds, intermediates, methods of making, and methods of use of these compounds as immunomodulators, for inducing or inhibit
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Page/Page column 118-119
(2008/06/13)
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- BIPHENYL CARBOXYLIC AMIDE P38 KINASE INHIBITORS
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Compounds of formula (I) or pharmaceutically acceptable derivatives thereof, and their use as pharmaceuticals, particularly as p38 kinase inhibitors.
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- Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas
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This invention relates to the use of a group of aryl ureas in treating cytokine mediated diseases and proteolytic enzyme mediated diseases, and pharmaceutical compositions for use in such therapy.
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- Inhibition of raf kinase using symmetrical and unsymmetrical substituted diphenyl ureas
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This invention relates to the use of a group of aryl ureas in treating raf mediated diseases, and pharmaceutical compositions for use in such therapy.
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- Salicylamides as serine protease inhibitors
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The present invention provides novel compounds of Formula I: its prodrug forms, or pharmaceutically acceptable salts thereof. The compounds of this invention are inhibitors of serine proteases, Urokinase (uPA), Factor Xa (FXa), and/or Factor VIIa (FVIIa),
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- Pyrimidofuroxans, their preparation and their use
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The present invention relates to pyrimidofuroxans of the general formula I STR1 in which A denotes STR2 where in each case the nitrogen atom is bonded via the C-4 and the carbon atom via the C-3 of the furoxan ring and the R radicals are defined as indicated in Claim 1, processes for their preparation and their use for the control and prevention of disorders of the cardiovascular system, in particular for the control and prevention of angina pectoris, and for the treatment of erectile dysfunctions.
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- Synthesis and antiviral activity of a series of HIV-1 protease inhibitors with functionality tethered to the P1 or P1'phenyl substituents: X-ray crystal structure assisted design
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By tethering of a polar hydrophilic group to the P1 or P1' substituent of a Phe-based hydroxyethylene isostere, the antiviral potency of a series of HIV protease inhibitors was improved. The optimum enhancement of anti-HIV activity was observed with the 4-morpholinylethoxy substituent. The substituent effect is consistent with a model derived from inhibitor docked in the crystal structure of the native enzyme. An X-ray crystal structure of the inhibited enzyme determined to 2.25 A verifies the modeling predictions.
- Thompson,Fitzgerald,Holloway,Emini,Darke,McKeever,Schleif,Quintero,Zugay,Tucker,Schwering,Homnick,Nunberg,Springer,Huff
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p. 1685 - 1701
(2007/10/02)
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