- Photoaffinity labeling of rat steroid 5α-reductase (isozyme-1) by a benzophenone derivative of a 4-methyl-4-azasteroid
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[1,2-3H]N-4(Benzylbenzoyl)-3-oxo-4-aza-4-methyl-5α-androstane-17β- carboxamide ([3H]-4MABP) has been synthesized as a photoaffinity probe of the steroid 5α-reductase isozyme-1 (5αR-1). Reversible binding of the probe to 5αR-1 in microsomal preparations yielded a reversible dissociation constant (K(d)) of ~3 nM, whereas inhibition experiments indicated that the probe had a 50% inhibition concentration of 4.4 nM and was a competitive inhibitor of the enzyme (K(i) ? 3 nM) with respect to testosterone. SDS- PAGE analysis of microsomal, detergent-solubilized, and (6.5%) polyethylene glycol-precipitated fractions of 5αR-1 photolyzed with [3H]4MABP in the presence of NADPH showed that the radioactivity was incorporated into a single protein band with a mass of 26 kDa (apparent molecular weight of 5αR- 1). UV photolysis was accompanied by an irreversible loss in enzyme activity, consistent with its covalent modification. Increasing the time of UV irradiation and concentration of [3H]4MABP indicated that the half-life and apparent K(d) for its photo insertion were ~3 min and 7.5 nM, respectively. Photolysis in the presence of a 20-fold excess of N,N-diethyl-4-aza-4- methyl-3-oxo-5α-androstune-17β-carboxamide or the 3-carboxysteroid SKF- 105111 resulted in partial protection of 5αR-1 from the probe, whereas minimal incorporation of radioactivity was observed in the absence of NADPH or in the presence of NADP+. The results indicated that [3H]4MABP is an effective probe of the steroid (D-ring) binding domain of 5αR-1.
- Taylor, Matthew F.,Bhattacharyya, Anjan K.,Rajagopalan, Krishnan,Hiipakka, Richard,Liao, Shutsung,Collins, Delwood C.
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Read Online
- Polar Radicals. 15. Interpretation of Substituent Effects on the Mechanism of Electrolytic Reduction of the Carbon-Halogen Bond in Series of Substituted Benzyl Halides
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The electrochemical polarographic reduction of a series of substituted benzyl chlorides and benzyl bromides showed half-wave potentials which gave excellent Hammett linear free-energy correlations for each series.These correlations were obtained using ?- substituent constants.The correlation with ?- suggests that the potential-determining electrochemical process involves carbon-halogen bond breaking or, alternatively, radical anion intermediate formation.The Hammett ρ values for each correlation were calculated; their magnitudes, Cl>Br, were in the inverse order of their reactivity toward chemical reduction.As in the case of trialkyltin hydride reduction, both ρ values were positive.The results of the polarographic electroreduction of benzyl iodide and benzylmercuric iodide confirmed the previously reported mechanism for reduction;namely, that the iodide underwent reaction with mercury to form benzylmercuric iodide, which was subsequently reduced, as was benzylmercuric iodide itself, by a process having two distinct polarographic waves.The half-wave potentials for the second wave (the wave at the most negative potential) for series of substituted benzyl iodides and benzylmercuric iodides were both found to give excellent Hammett correlation, having positive ρ values.The correlations were both obtained by using ?- substituent constants.The success of the use of these substituent constants was taken as a confirmation of the suggestion, previously made, that the second step in the electroreduction was the reduction of the benzylmercuryl radical, and suggests that the process is concerted with carbon-mercury bond rupture.
- Tanner, Dennis D.,Plambeck, James A.,Reed, Darwin W.,Mojelski, Thomas W.
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Read Online
- Development of a photoactivatable allosteric ligand for the M1 muscarinic acetylcholine receptor
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The field of G protein-coupled receptor drug discovery has benefited greatly from the structural and functional insights afforded by photoactivatable ligands. One G protein-coupled receptor subfamily for which photoactivatable ligands have been developed is the muscarinic acetylcholine receptor family, though, to date, all such ligands have been designed to target the orthosteric (endogenous ligand) binding site of these receptors. Herein we report the synthesis and pharmacological investigation of a novel photoaffinity label, MIPS1455 (4), designed to bind irreversibly to an allosteric site of the M1 muscarinic acetylcholine receptor; a target of therapeutic interest for the treatment of cognitive deficits. MIPS1455 may be a valuable molecular tool for further investigating allosteric interactions at this receptor.
- Davie, Briana J.,Sexton, Patrick M.,Capuano, Ben,Christopoulos, Arthur,Scammells, Peter J.
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Read Online
- Synthesis and characteristics of photopolymerized benzophenone
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Photopolymerization is extensively used in today's industrial field due to its advantages of rapid reaction, environmental friendly, energy saving and economical. Benzophenone is a most common photoinitiator (PI) using in photopolymerization because of its superior ability to initiate acrylate monomers. However, the intrinsic nature of initiator molecules is that they migrate out of polymer network, which limits its application, especially in the domain of food packaging materials. A polymerizable PI 4-methylbenzophenone acrylate (MBPAc) was synthesized by a facile procedure and characterized by 1H NMR, 13C NMR, and MS analyses. A systematic study of the photopolymerization kinetics of MBPAc was explored by the Real-Time Fourier Transform Infrared Spectrometer. The results show that the final conversion and photopolymerization rate of acrylate monomers are closely related to the factors of their chemical structure, viscosity, functionality and light intensity, which means MBPAc is an efficient PI. Ultraviolet-visible Spectrophotometer and vitro cytotoxicity measurement results indicate that the noncytotoxic MBPAc shows significantly lower migration than its analogue.
- Tang, Yunhui,Zhang, Yuxuan,Yang, Jinliang,Nie, Jun
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Read Online
- Surfaces and coating compositions having antifouling, antithrombotic, and antibacterial properties and methods of making
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Coating compositions, coated articles including the coating compositions, and methods of making the coating compositions and coated articles are provided. In some aspects, the coating compositions areapplied to a substrate having nitric oxide-releasing properties. The coating compositions can include copolymers having crosslinking agents that can be activated with mild UV light (about 345 nm to 365 nm) to avoid damaging the substrate while creating strong covalent bonds to the substrate. The copolymers can include hydrophilic repeat units, and in particular zwitterionic repeat units such as repeat units containing phosphorylcholine groups. In some aspects, the coating compositions are applied to a surface of a polymer substrate, wherein the polymer substrate had nitric oxide releasing properties. The coating compositions and the coated articles can have antifouling, antithrombotic, and/or antibacterial properties.
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Paragraph 0215-0216
(2020/11/23)
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- Development of a Raltegravir-based Photoaffinity-Labeled Probe for Human Immunodeficiency Virus-1 Integrase Capture
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Photoaffinity labeling (PAL) is one of the upcoming and powerful tools in the field of molecular recognition. It includes the determination of dynamic parameters, such as the identification and localization of the target protein and the site of drug binding. In this study, a photoaffinity-labeled probe for full-length human immunodeficiency virus-1 integrase (HIV-1 IN) capture was designed and synthesized, following the structure of the FDA-approved drug Raltegravir. This photoprobe was found to retain the HIV IN inhibitory potential in comparison with its parent molecule and demonstrates the ability to label the HIV-1 IN protein. Putative photoprobe/inhibitor binding sites near the catalytic site were then identified after protein digestion coupled to mass and molecular modeling analyses.
- Pala, Nicolino,Esposito, Francesca,Tramontano, Enzo,Singh, Pankaj Kumar,Sanna, Vanna,Carcelli, Mauro,Haigh, Lisa D.,Satta, Sandro,Sechi, Mario
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supporting information
p. 1986 - 1992
(2020/11/09)
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- Visible Light-Catalyzed Benzylic C-H Bond Chlorination by a Combination of Organic Dye (Acr+-Mes) and N-Chlorosuccinimide
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By combining "N-chlorosuccinimide (NCS)"as the safe chlorine source with "Acr+-Mes"as the photocatalyst, we successfully achieved benzylic C-H bond chlorination under visible light irradiation. Furthermore, benzylic chlorides could be converted to benzylic ethers smoothly in a one-pot manner by adding sodium methoxide. This mild and scalable chlorination method worked effectively for diverse toluene derivatives, especially for electron-deficient substrates. Careful mechanistic studies supported that NCS provided a hydrogen abstractor "N-centered succinimidyl radical,"which was responsible for the cleavage of the benzylic C-H bond, relying on the reducing ability of Acr?-Mes.
- Xiang, Ming,Zhou, Chao,Yang, Xiu-Long,Chen, Bin,Tung, Chen-Ho,Wu, Li-Zhu
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p. 9080 - 9087
(2020/08/14)
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- ANTIBACTERIAL HYDROPHILIC COMPOUND AND USE THEREOF
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The present disclosure provides an antibacterial hydrophilic compound. The antibacterial hydrophilic compound may react, induced by light through a hydrogen abstraction group in the structural formula thereof, with a C—H group and thus bind to a surface of a material having the C—H group (for example, chemical fibers such as polyester, chinlon, and the like; plastics, rubbers, and other similar materials), which can impart a durable antibacterial activity and hydrophilicity to the material. The antibacterial hydrophilic compound has a relatively strong binding force to the surface of the material without damaging the mechanical properties of the raw material. The present disclosure also provides a modified material that is modified by the antibacterial hydrophilic compound.
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Paragraph 0144
(2020/04/10)
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- Novel high-activity diphenyl ketone photoinitiator and preparation method thereof
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The invention belongs to the field of photosensitive high polymer materials, and provides a novel high-activity diphenyl ketone photoinitiator. Two diphenyl ketone derivatives are synthesized into a novel diphenyl ketone photoinitiator through synthesis reaction, so that ultraviolet absorption wavelength and absorption peak area of the photoinitiator are increased, a utilization rate on ultraviolet light is increased, the photoinitiating activity is greatly improved, and range of application is increased. The invention provides a preparation method for the novel diphenyl ketone photoinitiator,and the preparation method is simple in reaction process, is gentle in reaction condition, is simple in post-treatment, and is easy to purify.
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Paragraph 0031; 0034; 0037; 0040
(2019/02/19)
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- Antistatic compound, surface treatment method for material, and modified material
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The present invention provides an antistatic compound. The antistatic compound is obtained by chemically reacting a compound with the structural formula represented by L1' or L2' with a compound Q', and the compound Q' is one or more of a polyhydroxy compound, a polycarboxy compound and a polysulfonate compound; L1' and L2' are shown in the description; and in the formulas L1' and L2', r is 1 or 2, Y is one of a single bond, the oxygen atom, the sulfur atom, the selenium atom, -C(O)-, -SO2-, -NH- and a C1-3 alkylene group, R1 to R10 and R to R are respectively independently selected from the hydrogen atom, a halogen atom, a monovalent polar group and a substituted or unsubstituted monovalent C1-18 hydrocarbon group, and at least one of the R1 to R10 or R to R reacts with the compound Q' to achieve chemical bonding. The antistatic compound can be combined with -CH- group-containing materials such as polyester and nylon to make the materials have antistatic properties and dyeability without reducing the mechanical properties of the materials.
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Paragraph 0096; 0097
(2019/10/01)
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- Structure-Based Optimization of N-Substituted Oseltamivir Derivatives as Potent Anti-Influenza A Virus Agents with Significantly Improved Potency against Oseltamivir-Resistant N1-H274Y Variant
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Due to the emergence of highly pathogenic and oseltamivir-resistant influenza viruses, there is an urgent need to develop new anti-influenza agents. Herein, five subseries of oseltamivir derivatives were designed and synthesized to improve their activity toward drug-resistant viral strains by further exploiting the 150-cavity in the neuraminidases (NAs). The bioassay results showed that compound 21h exhibited antiviral activities similar to or better than those of oseltamivir carboxylate (OSC) against H5N1, H5N2, H5N6, and H5N8. Besides, 21h was 5- to 86-fold more potent than OSC toward N1, N8, and N1-H274Y mutant NAs in the inhibitory assays. Computational studies provided a plausible rationale for the high potency of 21h against group-1 and N1-H274Y NAs. In addition, 21h demonstrated acceptable oral bioavailability, low acute toxicity, potent antiviral activity in vivo, and high metabolic stability. Overall, the above excellent profiles make 21h a promising drug candidate for the treatment of influenza virus infection.
- Zhang, Jian,Murugan, Natarajan Arul,Tian, Ye,Bertagnin, Chiara,Fang, Zengjun,Kang, Dongwei,Kong, Xiujie,Jia, Haiyong,Sun, Zhuosen,Jia, Ruifang,Gao, Ping,Poongavanam, Vasanthanathan,Loregian, Arianna,Xu, Wenfang,Ma, Xiuli,Ding, Xiao,Huang, Bing,Zhan, Peng,Liu, Xinyong
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p. 9976 - 9999
(2018/12/11)
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- Intramolecular energy transfer and photoisomerization in stilbene dendrimers
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Stilbene dendrimers with energy harvesting chromophores, such as naphthalene and benzophenone, have been prepared and their photochemical and photophysical properties have been examined. These dendrimers underwent trans-cis mutual photoisomerization on excitation of the core stilbene or the peripheral naphthalene and benzophenone chromophores through several energy transfer processes, and photophysical processes such as intersystem crossing finally resulted in cis-trans isomerization of the core stilbene.
- Taima, Masahiro,Ishida, Yuka,Arai, Tatsuo
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supporting information
p. 1013 - 1023
(2017/09/07)
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- SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1
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The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): (Iar) wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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Page/Page column 842-843
(2018/01/20)
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- Conjugated dyes carrying N, N-dialkylamino and ketone groups: One-component visible light Norrish type II photoinitiators
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This work presents new conjugated dyes carrying N, N-dialkylamino and ketone groups for using as one-component Norrish type II visible light photoinitiators. The novel dyes without ketone group were also synthesized to compose two-component visible light photoinitiators for comparisons. The target dyes show the remarkable absorption in visible light region. Photo-differential scanning calorimetry was employed to study visible light photoinitiating polymerization kinetics of methyl methacrylate by new one-component photoinitiators and two-component photoinitiators respectively. The results suggest that the one-component photoinitiators showed much more efficient photoinitiating polymerization of methyl methacrylate than the two-component photoinitiating systems under visible light irradiation. The molecular weight of visible light photopolymer produced by the new photoinitiators was determined. The visible light photoinitiating mechanism of the one-component photoinitiators was studied by absorption and emission spectra, electron spin resonance spectra and cyclic voltammograms analysis.
- Ding, Ge,Jing, Chuan,Qin, Xiaozhuan,Gong, Yulong,Zhang, Xueping,Zhang, Shengtao,Luo, Ziping,Li, Hongru,Gao, Fang
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p. 456 - 467
(2016/12/09)
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- Stilbene-benzophenone dyads for free radical initiating polymerization of methyl methacrylate under visible light irradiation
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The AB and AB2 trans-stilbene-benzophenone dyads were synthesized through multi-step pathway. The target dyads showed remarkable absorption in visible light region. Visible light photoinitiating polymerization of methyl methacrylate by the new dyads was studied by photo-differential scanning calorimetry. The results suggested that the AB2 dyad showed more efficient photoinitiating polymerization of methyl methacrylate than the AB one under visible light irradiation. Furthermore, the new dyads yielded the greater visible light photoinitiaing polymerization effect than the intermolecular photoinitiating systems and the commercial photoinitiator titanocene respectively. The molecular weights of visible light photopolymers produced by the new dyads were determined by gel permeation chromatography. The visible light photoinitiating mechanism of the new dyads was analyzed by the static and transient absorption and emission spectra, electron spin resonance spectra and cyclic voltammograms. The thermal stabilities of the new dyads were further studied by differential scanning calorimetry and thermograving.
- Qin, Xiaozhuan,Ding, Ge,Gong, Yulong,Jing, Chuan,Peng, Guangyue,Liu, Shihong,Niu, Lanying,Zhang, Shengtao,Luo, Ziping,Li, Hongru,Gao, Fang
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- The benzoquinone derivatives and their use
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The invention provides a p-benzoquinone derivative and an application thereof. The p-benzoquinone derivative has the inhibitory activity on a plasminogen activator inhibitor-1 (PAI-1); on cellular level, the compound can inhibit the transfer ability of HepG2 liver cancer cells; and in-vitro experiments show that the compound has an inhibition effect on formation of fibrin clots. The p-benzoquinone derivative can be used as a medicine for treating tumors and thrombotic diseases.
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Paragraph 0122
(2016/11/17)
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- NOVEL POLYMERIC PHOTOINITIATORS AND PHOTOINITIATOR MONOMERS
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The present invention provides polymeric photoinitiators being co-polymers of photoinitiator monomers and at least one further monomer, as well as photoinitiator monomers being intermediates in the preparation of such polymeric photoinitiators. Additionally, there is provided polyacrylate obtained by radical polymerization of at least one acrylate monomer (Ac) in the presence of such polymeric photoinitiators. In the photoinitiator monomers and polymeric photoinitiators, a photoinitiator moiety, a hydrolytic stable linker and two polymerisable functional groups are incorporated into the photoinitiator structure.
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(2015/06/03)
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- PHOTOSENSITIVE COMPOSITION
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The present invention refers to attenuation or light irradiated number colored masking a substance such as a high-density film transmitting thick presence the nozzles less even in a case of a low energy dose curable a photosensitive composition and gives a cured article is defined to be in the, these compositions comprise photosensitive of the present invention (1) ～ (4) as disclosed is a photosensitive composition containing, radical disclosure number (A), number (C) base generation and number (B) acid generator at least 1 by the irradiation of the light active dog generates active species (H), (H) active species thereof disclosure number (A) radical is, number (B) acid generator or base generation number (C) reacts with the new active species (I) the registrant produces new active species by polymeric material (I) is performed by polymerization of (D), (I) or (H) active species thereof acid or base is characterized in that; (1) radical disclosure number (A) (2) acid generator or base generation number (C) number (B) (3) polymeric material (D) (4) number (E) colored, metal oxide powder (F) or metal powder (G).
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Paragraph 0309-0314
(2021/07/03)
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- A reversible and selective inhibitor of monoacylglycerol lipase ameliorates multiple sclerosis
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Monoacylglycerol lipase (MAGL) is the enzyme responsible for the inactivation of the endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL inhibitors show analgesic and tissue-protecting effects in several disease models. However, the few efficient and selective MAGL inhibitors described to date block the enzyme irreversibly, and this can lead to pharmacological tolerance. Hence, additional classes of MAGL inhibitors are needed to validate this enzyme as a therapeutic target. Here we report a potent, selective, and reversible MAGL inhibitor (IC50 = 0.18 mm) which is active in vivo and ameliorates the clinical progression of a multiple sclerosis (MS) mouse model without inducing undesirable CB1-mediated side effects. These results support the interest in MAGL as a target for the treatment of MS.
- Hernndez-Torres, Gloria,Cipriano, Mariateresa,Hedn, Erika,Bj?rklund, Emmelie,Canales, Angeles,Zian, Debora,Feli, Ana,Mecha, Miriam,Guaza, Carmen,Fowler, Christopher J.,Ortega-Gutirrez, Silvia,Lpez-Rodrguez, Maria L.
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supporting information
p. 13765 - 13770
(2015/01/16)
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- A scalable procedure for light-induced benzylic brominations in continuous flow
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A continuous-flow protocol for the bromination of benzylic compounds with N-bromosuccinimide (NBS) is presented. The radical reactions were activated with a readily available household compact fluorescent lamp (CFL) using a simple flow reactor design based on transparent fluorinated ethylene polymer (FEP) tubing. All of the reactions were carried out using acetonitrile as the solvent, thus avoiding hazardous chlorinated solvents such as CCl4. For each substrate, only 1.05 equiv of NBS was necessary to fully transform the benzylic starting material into the corresponding bromide. The general character of the procedure was demonstrated by brominating a diverse set of 19 substrates containing different functional groups. Good to excellent isolated yields were obtained in all cases. The novel flow protocol can be readily scaled to multigram quantities by operating the reactor for longer time periods (throughput 30 mmol h-1), which is not easily possible in batch photochemical reactors. The bromination protocol can also be performed with equal efficiency in a larger flow reactor utilizing a more powerful lamp. For the bromination of phenylacetone as a model, a productivity of 180 mmol h -1 for the desired bromide was achieved.
- Cantillo, David,De Frutos, Oscar,Rincon, Juan A.,Mateos, Carlos,Oliver Kappe
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supporting information
p. 223 - 229
(2014/01/17)
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- One-pot transformation of methylarenes into aromatic aldehydes under metal-free conditions
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On the basis of studies of the transformation of benzylic bromides into the corresponding aromatic aldehydes by treatment with N-methylmorpholine N-oxide, various methylarenes were treated either with DBDMH in the presence of AIBN in acetonitrile at reflux (Method A) or with NBS in CCl4 under irradiation with a tungsten lamp at 30 °C (Method B), followed by treatment with N-methylmorpholine N-oxide to provide aromatic aldehydes in good yields. These methods could be adopted in one-pot transformations of methylarenes into aromatic aldehydes under conditions free of less toxic reagents and transition metals. Copyright
- Tabata, Masayuki,Moriyama, Katsuhiko,Togo, Hideo
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p. 3402 - 3410
(2014/06/09)
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- Synthesis of structurally diverse diarylketones through the diarylmethyl sp3 C-H oxidation
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Under open-flask conditions, an efficient method to assemble a series of diversely functionalized diarylketones in the presence of commercially available NBS has been developed. Yields of up to 99% have been achieved employing diarylmethanes as starting material. Based on 18O-labeled experiment, the addition of stoichiometric water eventually leads to excellent yields in all carbonylation cases.
- He, Chao,Zhang, Xiaohui,Huang, Ruofeng,Pan, Jing,Li, Jiaqiang,Ling, Xuege,Xiong, Yan,Zhu, Xiangming
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supporting information
p. 4458 - 4462
(2014/08/05)
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- Revisiting the bromination of c-h bonds with molecular bromine by using a photo-microflow system
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The photobromination of C-H bonds by using molecular bromine was reinvestigated under microfluidic conditions. The continuous-flow method suppressed the production of dibrominated compounds and effectively produced the desired monobrominated products with high selectivity. Rapid bromination of benzylic substrates containing a photoaffinity azide group was achieved without any decomposition. Go with the (micro)flow: Photobromination of C-H bonds by using molecular bromine under microfluidic conditions has been investigated (see scheme). The continuous-flow method suppressed the production of dibrominated compounds and effectively produced the desired monobrominated compounds with high selectivity. Rapid bromination of benzylic substrates containing a photoaffinity azide group was achieved without any decomposition.
- Manabe, Yoshiyuki,Kitawaki, Yuriko,Nagasaki, Masahiro,Fukase, Koichi,Matsubara, Hiroshi,Hino, Yoshiko,Fukuyama, Takahide,Ryu, Ilhyong
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supporting information
p. 12750 - 12753
(2015/03/30)
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- Direct oxidative conversion of methylarenes into aromatic nitriles
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A variety of methylarenes were successfully converted into the corresponding aromatic nitriles in good to moderate yields by the treatment with NBS or DBDMH in the presence of a catalytic amount of AIBN or BPO, followed by the reaction with molecular iodine in aq NH3 in a one-pot procedure. The present reaction is a useful and practical transition-metal-free method for the preparation of aromatic nitriles from methylarenes.
- Tsuchiya, Daisuke,Kawagoe, Yuhsuke,Moriyama, Katsuhiko,Togo, Hideo
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supporting information
p. 4194 - 4197
(2013/09/12)
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- Structure-activity relationship of a new series of reversible dual monoacylglycerol lipase/fatty acid amide hydrolase inhibitors
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The two endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), play independent and nonredundant roles in the body. This makes the development of both selective and dual inhibitors of their inactivation an important priority. In this work we report a new series of inhibitors of monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH). Among them, (±)-oxiran-2-ylmethyl 6-(1,1′-biphenyl-4-yl)hexanoate (8) and (2R)-(-)-oxiran-2-ylmethyl(4-benzylphenyl)acetate (30) stand out as potent inhibitors of human recombinant MAGL (IC50 (8) = 4.1 μM; IC 50 (30) = 2.4 μM), rat brain monoacylglycerol hydrolysis (IC 50 (8) = 1.8 μM; IC50 (30) = 0.68 μM), and rat brain FAAH (IC50 (8) = 5.1 μM; IC50 (30) = 0.29 μM). Importantly, and in contrast to the other previously described MAGL inhibitors, these compounds behave as reversible inhibitors either of competitive (8) or noncompetitive nature (30). Hence, they could be useful to explore the therapeutic potential of reversible MAGL inhibitors.
- Cisneros, José A.,Bj?rklund, Emmelie,González-Gil, Inés,Hu, Yanling,Canales, ángeles,Medrano, Francisco J.,Romero, Antonio,Ortega-Gutiérrez, Silvia,Fowler, Christopher J.,López-Rodríguez, María L.
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supporting information; experimental part
p. 824 - 836
(2012/04/10)
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- Ugi reaction-assisted rapid assembly of affinity-based probes against potential protein tyrosine phosphatases
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The multi-component Ugi reaction has been employed to assemble a small library of affinity-based probes (AfBPs) that target potential protein tyrosine phosphatases. The probes showed good labelling of PTP1B and MptpB, and were subsequently used to label endogenous PTP1B in MCF-7 cell lysates.
- Ge, Jingyan,Cheng, Xiamin,Tan, Lay Pheng,Yao, Shao Q.
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supporting information; experimental part
p. 4453 - 4455
(2012/05/20)
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- Synthesis and structure-activity analysis of new phosphonium salts with potent activity against African trypanosomes
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A series of 73 bisphosphonium salts and 10 monophosphonium salt derivatives were synthesized and tested in vitro against several wild type and resistant lines of Trypanosoma brucei (T. b. rhodesiense STIB900, T. b. brucei strain 427, TbAT1-KO, and TbB48). More than half of the compounds tested showed a submicromolar EC50 against these parasites. The compounds did not display any cross-resistance to existing diamidine therapies, such as pentamidine. In most cases, the compounds displayed a good selectivity index versus human cell lines. None of the known T. b. brucei drug transporters were required for trypanocidal activity, although some of the bisphosphonium compounds inhibited the low affinity pentamidine transporter. It was found that phosphonium drugs act slowly to clear a trypanosome population but that only a short exposure time is needed for irreversible damage to the cells. A comparative molecular field analysis model (CoMFA) was generated to gain insights into the SAR of this class of compounds, identifying key features for trypanocidal activity.
- Taladriz, Andrea,Healy, Alan,Flores Pérez, Eddysson J.,Herrero García, Vanessa,Ríos Martínez, Carlos,Alkhaldi, Abdulsalam A. M.,Eze, Anthonius A.,Kaiser, Marcel,De Koning, Harry P.,Chana, Antonio,Dardonville, Christophe
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supporting information; experimental part
p. 2606 - 2622
(2012/06/01)
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- Triplet phenacylimidazoliums-catalyzed photocycloaddition of 1,4-dihydropyridines: An experimental and theoretical study
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The photocycloadditions of 1,4-dihydropyridines (DHPs) were achieved by using phenacylimidazoliums (PIms) as photosensitizers. Irradiation of DHPs 3a-g in the presence of PIms 1a-e and 2 performed an efficient formation of 3,9-diazatetraasteranes in shorter times under a lower power lamp. The mechanism of photocycloaddition catalyzed by PIm was studied by laser flash photolysis and theoretical DFT computation. These time-resolved results showed that the triplet excited states of PIms were generated with high efficiency and detected by their characteristic ultraviolet absorptions, which were quenched by DHP at almost diffusion controlled rate. Theoretical studies suggest that PIm is involved in the photocycloaddition process through the 3(DHP? PIm)* triplet complexes and assists the stabilization of intermediates. All subsequent steps are predicted to be favorable and exothermic, leading to the cage dimers.
- Zhu, Xiaohe,Li, Weipeng,Yan, Hong,Zhong, Rugang
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experimental part
p. 13 - 20
(2012/08/13)
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- Coatings for medical articles including natural biodegradable polysaccharides
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Biodegradable coatings that include natural biodegradable polysaccharides are described. The coating is formed from a plurality of natural biodegradable polysaccharides having pendent coupling groups.
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- SAR and lead optimization of an HIV-1 Vif-APOBEC3G axis inhibitor
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We describe structure-activity relationship and optimization studies of RN-18, an HIV-1 Vif-APOBEC3G axis inhibitor. Targeted modifications of RN-18 ring C, ring B, ring A, bridge A-B, and bridge B-C were performed to identify the crucial structural features, which generated new inhibitors with similar (4g and 4i) and improved (5, 8b, and 11) activities. Two potent water-soluble RN-18 analogues, 17 and 19, are also disclosed, and we describe the results of pharmacological studies with compound 19. The findings described here will be useful in the development of more potent Vif inhibitors and in the design of probes to identify the target protein of RN-18 and its analogues.
- Mohammed, Idrees,Parai, Maloy K.,Jiang, Xinpeng,Sharova, Natalia,Singh, Gatikrushna,Stevenson, Mario,Rana, Tariq M.
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supporting information; experimental part
p. 465 - 469
(2012/09/22)
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- Photobase generator
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The object of the present invention is to provide a photobase generator capable of efficiently generating amines (tertiary amines and amidine) high in catalytic activity by sensing light with a wavelength of from 350 to 500 nm (especially, from 400 to 500 nm). The present invention is a photobase generator characterized in being represented by general formula (1) or (2). Y+ is a quaternary ammonio group of general formula (3) to (5), and X? is a counter anion selected from among a borate anion, a phenolate anion, and a carboxylate anion.
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Page/Page column 38-39
(2013/02/27)
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- Synthetic approach to stop-codon scanning mutagenesis
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A general combinatorial mutagenesis strategy using common dimethoxytrityl-protected mononucleotide phosphoramidites and a single orthogonally protected trinucleotide phosphoramidite (Fmoc-TAG; Fmoc = 9-fluorenylmethoxycarbonyl) was developed to scan a gene with the TAG amber stop codon with complete synthetic control. In combination with stop-codon suppressors that insert natural (e.g., alanine) or unnatural (e.g., p-benzoylphenylalanine, Bpa) amino acids, a single DNA library can be used to incorporate different amino acids for diverse purposes. Here, we scanned TAG codons through part of the gene for a model four-helix bundle protein, Rop, which regulates the copy number of ColE1 plasmids. Alanine was incorporated into Rop for mapping its binding site using an in vivo activity screen, and subtle but important differences from in vitro gel-shift studies of Rop function are evident. As a test, Bpa was incorporated using a Phe14 amber mutant isolated from the scanning library. Surprisingly, Phe14Bpa-Rop is weakly active, despite the critical role of Phe14 in Rop activity. Bpa is a photoaffinity label unnatural amino acid that can form covalent bonds with adjacent molecules upon UV irradiation. Irradiation of Phe14Bpa-Rop, which is a dimer in solution like wild-type Rop, results in covalent dimers, trimers, and tetramers. This suggests that Phe14Bpa-Rop weakly associates as a tetramer in solution and highlights the use of Bpa cross-linking as a means of trapping weak and transient interactions.
- Nie, Lihua,Lavinder, Jason J.,Sarkar, Mohosin,Stephany, Kimberly,Magliery, Thomas J.
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experimental part
p. 6177 - 6186
(2011/06/22)
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- Synthesis and spectroscopy of novel branched fluorescent dyes containing benzophenone parts and the possibility as fluorescence probes
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This paper describes a new fluorescent family of branched dyes containing benzophenone unit including 4-N, N-diphenylamino-4′-phenacyl-stilbene (C1), 4,4′-di(4-benzoylphenylethylene)yl-triphenylamine (C2) and 4,4′,4″-tri(4-benzoylphenylethylene)yl-triphenylamine (C3). Benzophenone part is coupled with core through C-C double bond. The chemical structures of the derivatives are characterized with 1H and 13C nuclear magnetic resonance and elemental analysis. Strong π-π stacking interactions are discovered with the analysis of the X-ray crystallographic data of C1. The absorption maxima and emission maxima of the derivatives exhibit gradual bathochromic shift from C1 to C3. The optical density of C1, C2 and C3 are shown to be related to the number of branches. The changes of dipole moments between the excited and ground states for C1, C2 and C3 were estimated to be 4.356, 8.091 and 8.479 Derby, respectively by Lippert equation, confirming that the internal charge transfer (ICT) dominates the process of excited singlet state. The possibility as fluorescence probes of the derivatives on the estimation of what region of micelles interacting with samples was evaluated.
- Gao, Fang,Niu, Lanying,Hu, Nvdan,Wang, Jianchao,Li, Hongru,Zhang, Shengtao
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scheme or table
p. 149 - 159
(2012/04/23)
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- Two-photon optical properties of novel branched conjugated derivatives carrying benzophenone moiety with various electron donor-acceptor substituent groups
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This paper presents a range of novel new branched conjugated dyes containing benzophenone moiety. As compared with those of 4-(p-benzoyl-styrene) yl-4′-(styrene)yl-triphenylamine (C1) and 4-(p-benzoyl-styrene)yl- 4′-3,4,5-trimethoxyl-styrene)yl-triphenylamine (C2), the maximal linear absorption and emission wavelength of 4-(p-benzoyl-styrene)yl-4′- (p′-nitro-styrene)yl-triphenylamine (C3) displays red-shifted remarkably, While the fluorescence quantum yields of C3 are lower than those of C1 and C2 in various solvents. The fluorescence lifetimes of the derivatives were measured, and radiative and non-radiative transition constants of the derivatives were calculated. Two-photon absorption (TPA) optical data of the derivatives were measured by Ti:sapphire femtosecond laser tuning from 720 to 880 nm at intervals of 20 nm. TPA induced fluorescence emission of C3 is red-shifted with respected to that of C1 and C2. TPA cross sections of C3 are larger than those of C1 and C2 in various excited laser frequencies. TPA cross section of C2 and C3 are much larger than those of 3,4,5-(trimethoxylstyrene)yl-triphenylamine (C4) and 4-(p-nitrostyrene)yl-triphenylamine (C5) respectively under various near-IR Ti:sapphire femtosecond laser wavelength. C1 and C2 show similar one- and two- photon optical nature. Geometry optimization with ab initio method confirms that C3 has different electron density distribution, the energy levels in frontier orbitals, the dipole moment changes, the absorption and emission spectroscopy from those of C1 and C2. The cyclic voltammograms of the derivatives were detected in methylene chloride at various scan rates, and the energy of frontier orbials were estimated further from the redox potentials.
- Li, Hongru,Yang, Long,Liu, Jian,Wang, Chunfeng,Gao, Fang,Zhang, Shengtao
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scheme or table
p. 393 - 407
(2012/04/23)
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- TAILORED CONTROL OF SURFACE PROPERTIES BY CHEMICAL MODIFICATION
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A process for producing a substrate having an adhesive surface, which process comprises: (a) contacting the substrate with a carbene precursor, which carbene precursor is a compound of the following formula (1): whose substituent groups are SP defined herein, provided that when R is aryl or heteroaryl, said aryl or heteroaryl may be substituted by one, two, three, four or five groups, which groups are independently selected from various groups including -LB-WB; and (b) either: (i) when WA or WB comprises an adhesive functional group, generating a carbene reactive intermediate from the carbene precursor so that it reacts with the substrate to functionalise the surface, thereby yielding said substrate having an adhesive surface; or (ii) when WA or WB comprises a group which is a precursor of an adhesive functional group, generating a carbene reactive intermediate from the carbene precursor so that it reacts with the substrate to functionalise the surface, and (c) converting said group which is a precursor into an adhesive functional group thereby yielding said substrate having an adhesive surface. The invention further relates to carbene precursor compounds for use in the process, substrates produced by the process and to processes for preparing certain precursor compounds.
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Page/Page column 26-27
(2010/04/23)
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- Two-photon absorption properties of novel conjugated dyes containing a benzophenone unit
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A variety of new conjugated dyes bearing a benzophenone unit were synthesized, and the linear absorption and emission were determined. Two-photon absorption properties of the derivatives have been measured by a Ti:sapphire femtosecond laser tuning from 720 to 880 nm at intervals of 20 nm. One- and two-photon optical properties of the derivatives were found to be significantly dependent on their chemical structures.
- Liu, Jian,Gao, Fang,Yang, Long,Wang, Chunfeng,Li, Hongru,Zhang, Shengtao
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supporting information; experimental part
p. 324 - 325
(2010/07/06)
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- Environmentally benign electrophilic and radical bromination 'on water': H2O2-HBr system versus N-bromosuccinimide
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A H2O2-HBr system and N-bromosuccinimide in an aqueous medium were used as a 'green' approach to electrophilic and radical bromination. Several activated and less activated aromatic molecules, phenylsubstituted ketones and styrene were efficiently brominated 'on water' using both systems at ambient temperature and without an added metal or acid catalyst, whereas various non-activated toluenes were functionalized at the benzyl position in the presence of visible light as a radical activator. A comparison of reactivity and selectivity of both brominating systems reveals the H2O2-HBr system to be more reactive than NBS for benzyl bromination and for the bromination of ketones, while for electrophilic aromatic substitution of methoxy-substituted tetralone it was higher for NBS. Also, higher yields of brominated aromatics were observed when using H2O2-HBr 'on water'. Bromination of styrene reveals that not just the structure of the brominating reagent but the reaction conditions: amount of water, organic solvent, stirring rate and interface structure, play a key role in defining the outcome of bromination (dibromination vs bromohydroxylation). In addition, mild reaction conditions, a straightforward isolation procedure, inexpensive reagents and a lower environment impact make aqueous brominating methods a possible alternative to other reported brominating protocols.
- Podgor?ek, Ajda,Stavber, Stojan,Zupan, Marko,Iskra, Jernej
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experimental part
p. 4429 - 4439
(2009/10/09)
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- BIODEGRADABLE OCULAR IMPLANTS AND METHODS FOR TREATING OCULAR CONDITIONS
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Biodegradable ocular implants are described. The ocular implants include a bioactive agent that can be released within the eye to treat an ocular condition or indication. The implants can be used for the administration of a bioactive agent over prolonged periods of time. In some aspects the implants are formed of a matrix of natural biodegradable polysaccharides.
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Page/Page column 43-44
(2008/12/05)
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- Tissue graft materials containing biocompatible agent and methods of making and using same
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The invention provides implantable tissue graft materials composed of a collagenous tissue scaffold and a biocompatible agent bonded to the tissue scaffold via an activated photoreactive group. The invention further provides methods including steps of obtaining a tissue graft material comprising a collagenous tissue scaffold; contacting the collagenous tissue scaffold with a biocompatible agent composition that includes biocompatible agent and one or more photoreactive groups; and treating the collagenous tissue scaffold and biocompatible agent composition to activate the photoreactive groups and bond the biocompatible agent to the tissue scaffold via one or more activated photoreactive groups. Implantable prostheses formed of the tissue graft material are also contemplated.
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Page/Page column 17
(2010/11/30)
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- Biodegradable ocular implants and methods for treating ocular conditions
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Biodegradable ocular implants are described. The ocular implants include a bioactive agent that can be released within the eye to treat an ocular condition or indication. The implants can be used for the administration of a bioactive agent over prolonged periods of time. In some aspects the implants are formed of a matrix of natural biodegradable polysaccharides.
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- Synthesis of potentially photoactivatable coumarin derivatives via a 1,3-dipolar cycloaddition
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(Chemical Equation Presented) A copper (I)-catalyzed 1,3-dipolar cycloaddition reaction was used to prepare a series of mono and disubstituted 1,2,3-triazolyl-coumarins using a 1,3-cycloaddition ("Click Chemistry"). Starting coumarins were synthesized using classical or modified Pechmann's reaction. The propargyl group was introduced as either propargylether or as a propargylamide. Azides were prepared in a three steps procedure. Cycloaddition products, containing a coumarin and a photoactivatable moiety, were obtained in good yields.
- Chenot, Elodie-Denise,Rodriguez-Dominguez, Juan Carlos,Hannewald, Paul,Comel, Alain,Kirsch, Gilbert
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experimental part
p. 1429 - 1435
(2009/04/07)
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- Study of the absorption and emission spectroscopy of "A-B" type photosensitive compounds including two-photon chromophore and benzophenone moiety
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"A-B" type photosensitive compounds including two-photon chromophore and benzophenone moiety have been designed, synthesized and characterized. The UV-vis absorption and fluorescence emission of the compounds have been extensively studied in various solvents. The results show that the absorption of "A-B" type compounds displays obvious double absorption bands, one of which at short-wavelength is related to the benzophenone moiety, the other at long-wavelength is mainly contributed by chromophore. The emission of "A-B" type compounds at 500-700 nm shows an "unexpected" blue-shift comparing with that of the sole chromophore. The photosensitive compounds with amino group display strong emission in apolar solvents and have a low fluorescence quantum yields in polar solvents. In contrast, the compounds without amino group exhibit strong fluorescence emission in polar solvents, and low fluorescence quantum yields in apolar solvents. The fluorescence quantum yields of "A-B" type compounds are higher than those of the sole chromophore. The discoveries suggest that charge redistribution induced by the introduction of benzophenone moiety plays a key role on the absorption and emission spectroscopy.
- Gao, Fang,Hu, Nvdan,Xie, Ting,Cheng, Zhibin,Yang, Long,Liu, Xiaojiao,Li, Zedong,Wang, Xinfu,Li, Hongru,Li, Xueming
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body text
p. 1006 - 1012
(2009/02/02)
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- Asymmetric Sommelet-Hauser rearrangement of N-benzylic ammonium salts
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(Chemical Equation Presented) [2,3] over [1,2]: The asymmetric Sommelet-Hauser rearrangement of an ammonium salt derived from N-benzylic proline-derived or N-benzylic glycine (-)-8-phenylmenthol ester is shown to proceed with remarkably high levels of stereoselectivity. The method provides unique and efficient access to optically active α-aryl amino acid derivatives.
- Tayama, Eiji,Kimura, Hiroshi
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p. 8869 - 8871
(2008/09/19)
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- Synthesis and pharmacological evaluation of fluorescent and photoactivatable analogues of antiplasmodial naphthylisoquinolines
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The naphthylisoquinoline (NIQ) alkaloids from tropical Ancistrocladaceae and Dioncophyllaceae plants show high antiplasmodial activities in vitro and in vivo, even against chloroquine-resistant strains of the malaria pathogen. For the directed optimization of these activities, an investigation of the mode of action seems most rewarding. We have therefore embarked on the identification of the respective target protein in Plasmodium falciparum. For this purpose, we have developed a flexible pathway for the synthesis of a chemically divergent series of photoactive and fluorescent derivatives of such alkaloids and succeeded in preparing the first functionalized NIQ derivatives, 10, 12, and 35, suited for fluorescence and photoaffinity labeling experiments. Pharmacological investigations ensured that the modified alkaloid derivatives retained their antiplasmodial activity. The work may pave the way for a further improvement of the activity of these natural products and will thus increase their pharmacological potential as a valuable lead structure against the widespread tropical disease malaria.
- Bringmann, Gerhard,Gampe, Christian M.,Reichert, Yanina,Bruhn, Torsten,Faber, Johan H.,Mikyna, Martin,Reichert, Matthias,Leippe, Matthias,Brun, Reto,Gelhaus, Christoph
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p. 6104 - 6115
(2008/09/16)
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- Imidazolylmethylbenzophenones as highly potent aromatase inhibitors
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Suppression of tumor and plasma estrogen levels by inhibition of aromatase is one of the most effective treatments for post-menopausal breast cancer patients. Starting from an easy, synthetically accessible, benzophenone scaffold, a new class of potent aromatase inhibitors was synthesized, endowed with high selectivity with respect to 17α-hydroxylase/17,20-lyase (CYP17). Compounds 1b and 1d proved to be among the most potent inhibitors described so far.
- Gobbi, Silvia,Cavalli, Andrea,Negri, Matthias,Schewe, Katarzyna E.,Belluti, Federica,Piazzi, Lorna,Hartmann, Rolf W.,Recanatini, Maurizio,Bisi, Alessandra
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p. 3420 - 3422
(2008/02/12)
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- Coatings including natural biodegradable polysaccharides and uses thereof
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Biodegradable coatings and articles that include natural biodegradable polysaccharides are described. The coatings and articles are formed from a plurality of natural biodegradable polysaccharides having pendent coupling groups.
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- Free radical bromination by the H2O2-HBr system on water
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An aqueous solution of hydrogen peroxide and hydrogen bromide illuminated by a 40 W incandescent light bulb serves as a source of bromine radicals. Various substituted toluenes (H, Me, tBu, Br, COOEt, COPh, NO2) were brominated at the benzyl position. This haloperoxidase-like system for benzylic bromination does not require the presence of metal ions or an organic solvent for efficient conversion of methyl-arenes to benzyl bromides.
- Podgor?ek, Ajda,Stavber, Stojan,Zupan, Marko,Iskra, Jernej
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p. 7245 - 7247
(2007/10/03)
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- A chemical method for the convenient surface functionalisation of polymers
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A method for the application of carbenes as reactive intermediates for surface modification of polymeric substrates has been developed; the efficacy of the process has been demonstrated by irreversible dyeing of polystyrene, polythene, nylon, silica, and controlled pore glass, and to a limited extent, polytetrafluoroethylene. The Royal Society of Chemistry 2005.
- Awenat, Karim M.,Davis, Philip J.,Moloney, Mark G.,Ebenezer, Warren
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p. 990 - 992
(2007/10/03)
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- Formal intramolecular photoredox chemistry of meta-substituted benzophenones
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(Chemical Equation Presented) Photolysis of 3-(hydroxymethyl)benzophenone (1) in aqueous solution (pH -4 M) conditions. Evidence suggests that the highly efficient (Φ ～ 0.6) reaction involves a unimolecular mechanism and an overall formal intramolecular photoredox process, which requires electronic communication between the 1,3-positions of the benzene ring, an unprecedented example of the photochemical meta effect. The photoredox reaction was not observed in organic solvents, where only photoreduction of the benzophenone moiety was observed.
- Mitchell, Devin,Lukeman, Matthew,Lehnherr, Dan,Wan, Peter
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p. 3387 - 3389
(2007/10/03)
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- Process for surface functionalsation of polymeric substrates using diaryl carbenes as reactive intermediates
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An alternative technique whereby highly reactive carbene or nitrene species are generated from inert precursors under less harsh photolytic, and sometimes thermolytic, conditions has also been investigated for application to dyeing and other surface modifying processes of various natural and synthetic polymers. The chemistry of cargenes and nitrenes is well documented, and these reactive entities are known to form covalent bonds with many types of functional group groups. The application of these species to the surface modification or organic solids using different approaches both for the generation of the required carbenes or nitrenes, and for their reaction with the solid surface has been reported. Interestingly, although nitrenes (often generated from an azide or sulfonylazide precursor under photolytic or thermolytic conditions) are more stable, and therefore less reactive, than their carbene analogues, they have used much more widely for the dyeing of polymeric substrates.
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- Parallel synthesis of DAPT derivatives and their γ-secretase- inhibitory activity
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Parallel synthesis of the C-terminal-modified DAPT (1) derivatives was accomplished utilizing our novel resin 7. Condensation reaction of the N-acylamino acid 10 with the amines 11a-o proceeded smoothly to give the corresponding amides 6a-o without any epimerization. Among the analogues, the benzophenonemethyl amide derivative 6o showed 30 times more potent activity than the original DAPT (1).
- Kan, Toshiyuki,Tominari, Yusuke,Rikimaru, Kentaro,Morohashi, Yuichi,Natsugari, Hideaki,Tomita, Taisuke,Iwatsubo, Takeshi,Fukuyama, Tohru
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p. 1983 - 1985
(2007/10/03)
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