- Tyramine fragment binding to BACE-1
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Fragment screening revealed that tyramine binds to the active site of the Alzheimer's disease drug target BACE-1. Hit expansion by selection of compounds from the Roche compound library identified tyramine derivatives with improved binding affinities as m
- Kuglstatter, Andreas,Stahl, Martin,Peters, Jens-Uwe,Huber, Walter,Stihle, Martine,Schlatter, Daniel,Benz, Joerg,Ruf, Armin,Roth, Doris,Enderle, Thilo,Hennig, Michael
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Read Online
- Lysosome-Targeted Bioprobes for Sequential Cell Tracking from Macroscopic to Microscopic Scales
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Longitudinal tracking of living cells is crucial to understanding the mechanism of action and toxicity of cell-based therapeutics. To quantify the presence of administered cells in the host tissue without sacrifice of animals, labeling of the target cells
- Park, G. Kate,Lee, Jeong Heon,Levitz, Andrew,El Fakhri, Georges,Hwang, Nathaniel S.,Henary, Maged,Choi, Hak Soo
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Read Online
- Investigation on the synthesis of new 3-[4-(Arylalkoxy)phenylethyl]-2-thioxo-1,3-thiazolidin-4-ones and their biological evaluation against cancer cells
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(Figure Presented) Herein, we report on the 5-step synthesis of new 3-[4-(arylalkoxy)phenylethyl]-2-thioxo-1,3-thiazolidin-4-ones without 5-arylidene fragments starting from tyramine The construction involved protection with Boc2O, regioselective O-alkyla
- Dago, Camille Déliko,N’ta Ambeu, Christelle,Coulibaly, Wacothon Karime,Békro, Yves-Alain,Mamyrbekova-Bekro, Janat A.,Le Guével, Rémy,Corlu, Anne,Bazureau, Jean-Pierre
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Read Online
- Bactericidal compound based on exogenous metabolite of xanthomonas, and preparation method and application of bactericidal compound
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The invention discloses a bactericidal compound based on an exogenous metabolite of xanthomonas and a preparation method and application of the bactericidal compound. The bactericidal compound is a compound MB or a compound DB. The structural formulas of the compound MB and the compound DB are as shown in the specification. According to the invention, in order to solve the technical problems that an existing broad-spectrum bactericide generates membrane resistance and is difficult to pass through a cell membrane, a whole genome metabolic network model of xanthomonas is established, a specific exogenous metabolite tyramine of xanthomonas is screened and identified, and tyramine and an existing bactericide, namely luteolin or isoprothiolane are spliced respectively to synthesize the compound MB or the compound DB. The two compounds can specifically inhibit growth of xanthomonas, so the problem that a broad-spectrum bactericide generates membrane resistance is effectively solved, an inhibition rate is remarkably increased, the dosage of the bactericide is effectively reduced. The method is low in cost and high in efficiency, and has wide application prospects and economic values.
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Paragraph 0076-0080
(2021/07/14)
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- Chichibabin/isoChichibabin pyridinium synthesis of ma'edamines C and D
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Ma'edamines C and D were isolated from an Okinawan marine sponge and exhibited a unique tetrasubstituted pyridinium skeleton. The proposed biosynthetic pathway is similar to that of desmosine and isodesmosine, which are elastin-crosslinking amino acids. In this study, first total synthesis of ma'edamines C and D was achieved via Pr(OTf)3-promoted Chichibabin/isoChichibabin pyridinium synthesis starting from the corresponding aldehydes and amine.
- Hirose, Mika,Tanaka, Nao,Usuki, Toyonobu
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supporting information
(2021/06/22)
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- Generation of a quenched phosphonate activity-based probe for labelling the active KLK7 protease
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Kallikrein 7 (KLK7) is a chymotrypsin-like serine protease with established roles in skin diseases like the rare Netherton syndrome, an overdesquamating and inflammatory condition, but also common atopic dermatitis, and a potential drug target for these a
- Bisyris, Evangelos,Kordopati, Golfo G.,Magriotis, Plato A.,Matsoukas, Minos,Pampalakis, Georgios,Sotiropoulou, Georgia,Zingkou, Eleni
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supporting information
p. 6834 - 6841
(2021/08/20)
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- COMPOSITION AND METHODS FOR TUMOR IMAGING AND TREATMENT
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Radioisotope-labeled small molecule activity-based probes that target the cancer associated serine hydrolase neutral cholesterol ester hydrolase 1 (NCEH1) are described. The probes can undergo a reaction with the NCEH1, resulting in covalent bonding of a
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Paragraph 0125
(2021/11/13)
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- 6-amino-4-(4-phenoxyphenylethylamino)quinazoline derivative as well as preparation method and application thereof
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The invention belongs to the technical field of medicines, and particularly relates to a 6-amino-4-(4-phenoxyphenylethylamino)quinazoline (QNZ) derivative as well as a preparation method and application thereof. According to the invention, a series of QNZ
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Paragraph 0036-0038
(2021/01/24)
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- Development of specific and selective bactericide by introducing exogenous metabolite of pathogenic bacteria
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The widespread and repeated use of broad-spectrum bactericides has led to an increase in resistance. Developing novel broad-spectrum bactericides cannot solve the resistance problem, and may even aggravate it. The design of specific and selective bactericides has become urgent. A specific bactericidal design strategy was proposed by introducing exogenous metabolites in this study. This strategy was used to optimize two known antibacterial agents, luteolin (M) and Isoprothiolane (D), against Xoo. Based on the prodrug principles, target compound MB and DB were synthesized by combing M or D with exogenous metabolites, respectively. Bactericidal activity test results demonstrated that while the antibacterial ability of target compounds was significantly improved, their selectivity was also well enhanced by the introducing of exogenous metabolites. Comparing with the original compound, the antibacterial activity of target compound was significantly increased 92.0% and 74.5%, respectively. The optimized target compounds were more easily absorbed, and the drug application concentrations were much lower than those of the original agents, which would greatly reduce environmental pollution and relieve resistance risk. Our proposed strategy is of great significance for exploring the specific and selective bactericides against other pathogens.
- Cao, Min-Hui,Chu, Xin-Yi,Liang, Xiao-Long,Liang, Zhan-Min,Ruan, Yao,Tang, Bao-He,Zhang, Hong-Yu,Zhang, Qing-Ye
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- In Vivo Imaging of the Tumor-Associated Enzyme NCEH1 with a Covalent PET Probe
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Herein, we report the development of an 18F-labeled, activity-based small-molecule probe targeting the cancer-associated serine hydrolase NCEH1. We undertook a focused medicinal chemistry campaign to simultaneously preserve potent and specific
- Bhuiyan, Mohammed,Chang, Jae Won,Chen, Chin-Tu,Fathi, Shaghayegh,Freifelder, Richard,Leoni, Lara,Li, Gang,McCutcheon, David C.,Moellering, Raymond E.,Tsai, Hsiu-Ming,Zhang, Hannah J.
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supporting information
p. 15161 - 15165
(2020/06/30)
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- Structure-Activity Relationship Studies of α-Ketoamides as Inhibitors of the Phospholipase A and Acyltransferase Enzyme Family
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The phospholipase A and acyltransferase (PLAAT) family of cysteine hydrolases consists of five members, which are involved in the Ca2+-independent production of N-acylphosphatidylethanolamines (NAPEs). NAPEs are lipid precursors for bioactive N-acylethanolamines (NAEs) that are involved in various physiological processes such as food intake, pain, inflammation, stress, and anxiety. Recently, we identified α-ketoamides as the first pan-active PLAAT inhibitor scaffold that reduced arachidonic acid levels in PLAAT3-overexpressing U2OS cells and in HepG2 cells. Here, we report the structure-activity relationships of the α-ketoamide series using activity-based protein profiling. This led to the identification of LEI-301, a nanomolar potent inhibitor for the PLAAT family members. LEI-301 reduced the NAE levels, including anandamide, in cells overexpressing PLAAT2 or PLAAT5. Collectively, LEI-301 may help to dissect the physiological role of the PLAATs.
- Zhou, Juan,Mock, Elliot D.,Al Ayed, Karol,Di, Xinyu,Kantae, Vasudev,Burggraaff, Lindsey,Stevens, Anna F.,Martella, Andrea,Mohr, Florian,Jiang, Ming,Van Der Wel, Tom,Wendel, Tiemen J.,Ofman, Tim P.,Tran, Yvonne,De Koster, Nicky,Van Westen, Gerard J.P.,Hankemeier, Thomas,Van Der Stelt, Mario
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p. 9340 - 9359
(2020/10/19)
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- triAZOLOtriAZINE DERIVATIVES AS A2A RECEPTOR ANTAGONISTS
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The present invention provides triazolotriazine derivatives of formula (1) as A2A receptor antagonists. Compounds of formula (1) and pharmaceutical compositions including the compounds can be used for the treatment of disorders related to A2A receptor hyperfunctioning, such as certain types cancers. Compounds of formula (1) and methods of preparing the compounds are disclosed in the invention.
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Page/Page column 55-56
(2020/01/24)
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- Molecular recognition of bisphosphonate-based drugs by di-zinc receptors in aqueous solution and on gold nanoparticles
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Metal-based anion receptors have several important applications in sensing, separation and transport of negatively charged species. Amongst these receptors, di-zinc(ii) complexes are of particular interest for the recognition of oxoanions, in particular phosphate derivatives. Herein we report the synthesis of a di-zinc(ii) receptor and show that it has high affinity and selectivity for bisphosphonates such as alendronate and etidronate - which are used to treat a number of skeletal disorders as well as showing interesting anticancer properties. The binding mode of the di-zinc(ii) receptor with alendronate and etidronate has been unambiguously established by single crystal X-ray crystallography. In addition, by modifying the backbone of the receptor, we show that the drug-loaded receptor can be attached onto gold nanoparticles as potential drug-delivery vehicles.
- Chan, Tiffany G.,Torres-Huerta, Aaron,Vilar, Ramon,White, Andrew J. P.
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supporting information
p. 5939 - 5948
(2020/05/25)
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- Deacetylative Amination of Acetyl Arenes and Alkanes with C-C Bond Cleavage
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The Br?nsted acid-catalyzed synthesis of primary amines from acetyl arenes and alkanes with C-C bond cleavage is described. Although the conversion from an acetyl group to amine has traditionally required multiple steps, the method described herein, which uses an oxime reagent as an amino group source, achieves the transformation directly via domino transoximation/Beckmann rearrangement/Pinner reaction. The method was also applied to the synthesis of γ-aminobutyric acids, such as baclophen and rolipram.
- Hyodo, Kengo,Hasegawa, Genna,Maki, Hiroya,Uchida, Kingo
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p. 2818 - 2822
(2019/04/25)
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- Hitting on the move: Targeting intrinsically disordered protein states of the MDM2-p53 interaction
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Intrinsically disordered proteins are an emerging class of proteins without a folded structure and currently disorder-based drug targeting remains a challenge. p53 is the principal regulator of cell division and growth whereas MDM2 consists its main negative regulator. The MDM2-p53 recognition is a dynamic and multistage process that amongst other, employs the dissociation of a transient α-helical N-terminal ‘‘lid’’ segment of MDM2 from the proximity of the p53-complementary interface. Several small molecule inhibitors have been reported to inhibit the formation of the p53-MDM2 complex with the vast majority mimicking the p53 residues Phe19, Trp23 and Leu26. Recently, we have described the transit from the 3-point to 4-point pharmacophore model stabilizing this intrinsically disordered N-terminus by increasing the binding affinity by a factor of 3. Therefore, we performed a thorough SAR analysis, including chiral separation of key compound which was evaluated by FP and 2D NMR. Finally, p53-specific anti-cancer activity towards p53-wild-type cancer cells was observed for several representative compounds.
- Neochoritis, Constantinos G.,Atmaj, Jack,Twarda-Clapa, Aleksandra,Surmiak, Ewa,Skalniak, Lukasz,K?hler, Lisa-Maria,Muszak, Damian,Kurpiewska, Katarzyna,Kalinowska-T?u?cik, Justyna,Beck, Barbara,Holak,D?mling, Alexander
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supporting information
(2019/08/20)
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- Anti-Parasite Activity of Novel 3,5-Diiodophenethyl-benzamides
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Novel iodotyramides with para-substituted benzoic acids were synthesized via electrophilic aromatic substitutions and amide coupling via N,N'-diisopropylcarbodiimide (DIC) in dimethylformamide (DMF). All derivatives were in vitro screened against U-937 ma
- Restrepo, Manuel Pastrana,Surmay, Verónica Surmay,Jaramillo, Elkin Galeano,Restrepo, Sara Robledo
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p. 116 - 123
(2018/12/13)
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- A process for preparing a broad pH fluorescent probe of the organic compound and use thereof (by machine translation)
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The present invention discloses a process for the preparation of a wide range of fluorescent probe in the pH of the organic compound, the organic compound can be produced according to the actual need to carry out any proportion of combination, and can be fixed in the hydrophilic high polymer further preparing and detecting water environment acidity and alkalinity of the product. The product can be realized to the pH value of the continuous measuring, thereby greatly improving the efficiency, sensitivity and repeatability. (by machine translation)
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Paragraph 0097; 0098
(2018/04/03)
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- Substituted pyrimidine compound and use thereof (by machine translation)
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The invention discloses a broad-spectrum bactericidal killing activity of substituted pyrimidine compound, structure such as formula (I) as shown: In the type of each substituent is as defined in the specification. The compounds of this invention have broad-spectrum sterilization insecticidal or acaricidal activity, the cucumber downy mildew, corn rust, wheat powdery mildew, rice blast, cucumber gray mold disease such as has fine control effects, in particular to the cucumber downy mildew, corn rust, such as rice blast control effect better; Diamondback moth, sticky, aphid and preparing fuel also have fine control effects, at a very low dosage can be obtained very good results. (by machine translation)
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Paragraph 0471; 0472; 0473
(2018/05/07)
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- BENZOTHIOPHENE ESTROGEN RECEPTOR MODULATORS
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This invention is a benzothiophene estrogen receptor modulator or its pharmaceutically acceptable salt or a pharmaceutically acceptable composition thereof to treat an estrogen-related medical disorder.
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Paragraph 0619-0620
(2018/08/29)
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- Photoinduced Vitamin B12-Catalysis for Deprotection of (Allyloxy)arenes
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Vitamin B12 is a natural cobalt complex that, while reduced to the "supernucleophilic" Co(I) form, can easily react with electrophiles via an SN2 mechanism. It is also shown to react via an SN2′ mechanism with allylic compounds allowing for photochemical deprotection of (allyloxy)arenes. A sustainable alternative to commonly used noble metal-catalyzed deprotection reactions is presented.
- Giedyk, Maciej,Turkowska, Joanna,Lepak, Sandra,Marculewicz, Marcin,ó Proinsias, Keith,Gryko, Dorota
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supporting information
p. 2670 - 2673
(2017/05/24)
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- [TPA][Pro] ionic liquid as efficient reaction medium for N-tert-Boc protection of amines
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A facile and efficient N-tert-Boc protection of amines is described by the reaction of various primary, secondary, benzylic and aryl amines with di-tert-butyl dicarbonate in the ionic liquid [TPA][Pro] at room temperature. All the N-tert-butylcarbamates are afforded in excellent yields. A catalyst-free method was developed and the ionic liquid [TPA][Pro] can be recovered and reused for several times without loss of its activity.
- Vijaya Durga,Rambabu,Srinivasa Reddy,Hari Babu
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p. 1313 - 1316
(2017/05/02)
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- Fluoro-Hydroxyphenethylguanidines: Efficient Synthesis and Comparison of Two Structural Isomers as Radiotracers of Cardiac Sympathetic Innervation
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Fluorine-18 labeled phenethylguanidines are currently under development in our laboratory as radiotracers for quantifying regional cardiac sympathetic nerve density using PET imaging techniques. In this study, we report an efficient synthesis of 18/
- Jung, Yong-Woon,Jang, Keun Sam,Gu, Guie,Koeppe, Robert A.,Sherman, Phillip S.,Quesada, Carole A.,Raffel, David M.
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p. 1530 - 1542
(2017/07/24)
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- PROPENAMIDE THIOPHENE DERIVATIVES AS FLAVIVIRUS INHIBITORS AND THEIR USE
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The present invention deals with new flavivirus inhibitors, compositions comprising said inhibitors and methods for the treatment of disorders related to a viral infection, such as a disease due to a flavivirus infection, comprising administering said inhibitors.
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Page/Page column 27
(2017/07/06)
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- A solution for detecting metal ion content of organic compound and use thereof
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The invention relates to organic compounds used for detecting metal ion contents in solutions. The organic compounds can be used for biomedicine, environment monitoring, and the like. By introduction of color developing groups or fluorophores into ortho p
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Paragraph 0062; 0151; 0152; 0153
(2017/09/26)
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- Oximido-containing pyrimidine compound and application thereof
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The invention belongs to the field of agricultural fungus-killing, insect-killing and mite-killing agents and particularly relates to a novel oximido-containing pyrimidine compound and application thereof. The structure of the oximido-containing pyrimidine compound is shown in the structural formula I shown in the specification, and definitions of all substituent groups in the formula are shown in the specification. The compound has broad-spectrum fungus-killing, insect-killing and mite-killing activity, has an excellent preventing and treating effect on plutella xylostella, armyworms, aphids, tetranychus cinnabrinus and the like, especially has a better preventing effect on the aphids and the tetranychus cinnabrinu, also has an excellent preventing and treating effect on cucumber downy mildew, puccinia polysora, wheat powdery mildew, rice blast and anthracnose, and can obtain a good effect under a low dose. The compound further has the advantages of being simple in preparation method and the like.
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Paragraph 0693; 0694; 0695
(2017/07/31)
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- Amine compounds as fungicides
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The present invention discloses use of an amine compound as a bactericide, the compound has a structure as shown in (I), and the substituent groups in the (I) are as defined in the specification. The compound as shown in the (I) or a salt thereof is espec
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Paragraph 0257; 0258; 0259; 0260
(2017/04/20)
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- A novel quinazoline-based analog induces G2/M cell cycle arrest and apoptosis in human A549 lung cancer cells via a ROS-dependent mechanism
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6-amino-4-(4-phenoxyphenylethylamino)quinazoline (QNZ) is an excellent quinazoline-containing NF-κB inhibitor also acting as a novel anticancer agent. Considering both the medicinal significance of quinazoline scaffold and the tunable functionality of Mic
- Shi, Hailong,Li, Yan,Ren, Xiaorong,Zhang, Yaohong,Yang, Zhen,Qi, Chenze
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p. 314 - 320
(2017/04/04)
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- Multicomponent, fragment-based synthesis of polyphenol-containing peptidomimetics and their inhibiting activity on beta-amyloid oligomerization
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A new and short fragment-based approach towards artificial (but "natural-based") complex polyphenols has been developed, exploiting the Ugi multicomponent reaction of phenol-containing simple substrates. The resulting library of compounds has been tested
- Lambruschini, Chiara,Galante, Denise,Moni, Lisa,Ferraro, Francesco,Gancia, Giulio,Riva, Renata,Traverso, Alessia,Banfi, Luca,D'Arrigo, Cristina
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p. 9331 - 9351
(2017/11/22)
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- A peripheral single-substituted zinc phthalocyanine complex and its adriamycin conjugate (by machine translation)
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The invention discloses a peripheral single-substituted zinc phthalocyanine complex and its adriamycin conjugate, and methods for their preparation and use, which belongs to the technical field of a photosensitizer and pharmaceutical preparation. The resu
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Paragraph 0032
(2016/10/09)
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- Substituted thienopyrimidinamine compound with insecticidal and acaricidal activity, and application thereof
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The invention discloses an application of a substituted thienopyrimidinamine compound represented by general formula I shown in the specification as an insecticidal and acaricidal agent. All substituent groups in the formula I are defined as in the specification. The compound has wide-spectrum insecticidal and acaricidal activity, is highly effective to lepidoptera pests, Homoptera pests and mites, has especially good activity on aphids, carminespider mites, diamondback moths and armyworms, and has a very good control effect under a very low dosage.
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Paragraph 0190; 0191; 0192
(2016/10/08)
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- 5-Alkyloxytryptamines are membrane-targeting, broad-spectrum antibiotics
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Antibiotic adjuvant therapy represents an exciting opportunity to enhance the activity of clinical antibiotics by co-dosing with a secondary small molecule. Successful adjuvants decrease the concentration of antibiotics used to defeat bacteria, increase activity (in some cases introducing activity against organisms that are drug resistant), and reduce the frequency at which drug-resistant bacteria emerge. We report that 5-alkyloxytryptamines are a new class of broad-spectrum antibacterial agents with exciting activity as antibiotic adjuvants. We synthesized 5-alkyloxytryptamine analogs and found that an alkyl chain length of 6–12 carbons and a primary ammonium group are necessary for the antibacterial activity of the compounds, and an alkyl chain length of 6–10 carbons increased the membrane permeability of Gram-positive and Gram-negative bacteria. Although several of the most potent analogs also have activity against the membranes of human embryonic kidney cells, we demonstrate that below the minimum inhibitory concentration (MIC)—where mammalian cell toxicity is low—these compounds may be successfully used as adjuvants for chloramphenicol, tetracycline, ciprofloxacin, and rifampicin against clinical strains of Salmonella typhimurium, Acinetobacter baumannii and Staphylococcus aureus, reducing MIC values by as much as several logs.
- Faulkner, Katherine C.,Hurley, Katherine A.,Weibel, Douglas B.
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supporting information
p. 5539 - 5544
(2016/11/09)
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- Biomimetic deiodination of thyroid hormones and iodothyronamines-a structure-activity relationship study
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Mammalian selenoenzymes, iodothyronine deiodinases (DIOs), catalyze the tyrosyl and phenolic ring deiodination of thyroid hormones (THs) and play an important role in maintaining the TH concentration throughout the body. These enzymes also accept the decarboxylated thyroid hormone metabolites, iodothyronamines (TAMs), as substrates for deiodination. Naphthalene-based selenium and/or sulphur-containing small molecules have been shown to mediate the regioselective tyrosyl ring deiodination of thyroid hormones and their metabolites. Herein, we report on the structure-activity relationship studies of a series of peri-substituted selenium-containing naphthalene derivatives for the deiodination of thyroid hormones and iodothyronamines. Single crystal X-ray crystallographic and 77Se NMR spectroscopic studies indicated that the intramolecular Se?X (X = N, O and S) interactions play an important role in the deiodinase activity of the synthetic mimics. Furthermore, the decarboxylated metabolites, TAMs, have been observed to undergo slower tyrosyl ring deiodination than THs by naphthyl-based selenium and/or sulphur-containing synthetic deiodinase mimics and this has been explained on the basis of the strength of Se?I halogen bonding formed by THs and TAMs.
- Mondal, Santanu,Mugesh, Govindasamy
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supporting information
p. 9490 - 9500
(2016/10/22)
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- Ezrin inhibitors and methods of making and using
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The invention encompasses compound and pharmaceutical composition comprising the compound of the following Formula (I): or pharmaceutically acceptable salts or prodrugs thereof, that are useful for inhibiting ezrin protein in a cell or for inhibiting the growth of a cancer cell.
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Page/Page column 56
(2017/01/05)
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- HEPATITIS B CORE PROTEIN ALLOSTERIC MODULATORS
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ABSTRACT The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound.
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Paragraph 000343
(2015/10/05)
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- Synthesis and pharmacological evaluation of dual acting ligands targeting the adenosine A2A and dopamine D2 receptors for the potential treatment of parkinsons disease
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A relatively new strategy in drug discovery is the development of dual acting ligands. These molecules are potentially able to interact at two orthosteric binding sites of a heterodimer simultaneously, possibly resulting in enhanced subtype selectivity, higher affinity, enhanced or modified physiological response, and reduced reliance on multiple drug administration regimens. In this study, we have successfully synthesized a series of classical heterobivalent ligands as well as a series of more integrated and drug-like dual acting molecules, incorporating ropinirole as a dopamine D2 receptor agonist and ZM 241385 as an adenosine A2A receptor antagonist. The best compounds of our series maintained the potency of the original pharmacophores at both receptors (adenosine A2A and dopamine D2). In addition, the integrated dual acting ligands also showed promising results in preliminary blood-brain barrier permeability tests, whereas the classical heterobivalent ligands are potentially more suited as pharmacological tools.
- J?rg, Manuela,May, Lauren T.,Mak, Frankie S.,Lee, Kiew Ching K.,Miller, Neil D.,Scammells, Peter J.,Capuano, Ben
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supporting information
p. 718 - 738
(2015/01/30)
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- SUBSTITUTED PYRIMIDINE COMPOUND AND USES THEREOF
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Disclosed is a substituted pyrimidine compound having a structure as represented by formula PY. See the description for the definition of each substituent in the formula.The compound of the present invention provides broad-spectrum bactericidal, pesticidal, and acaricidal activities, provides great control effects against plant diseases such as cucumber downy mildew,corn rust,wheat powdery mildew, rice blast,and cucumber gray mold, specifically provides improved control effects against cucumber downy mildew, corn rust, wheat powdery mildew, and rice blast, provides great control effects against aphid, carmine spider mite, diamondback moth, and armyworm, and acquires great effects at a minimal dosage.The compound of the present invention aloso provides characteristics such as a simplified preparation method.
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Paragraph 0467; 0468
(2015/09/23)
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- Mixed alkyl aryl phosphonate esters as quenched fluorescent activity-based probes for serine proteases
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Activity-based probes (ABPs) are powerful tools for the analysis of active enzyme species in whole proteomes, cells or animals. Quenched fluorescent ABPs (qABPs) can be applied for real time imaging, allowing the visualization of dynamic enzyme activation
- Serim, Sevnur,Baer, Philipp,Verhelst, Steven H. L.
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p. 2293 - 2299
(2015/03/04)
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- Tailored near-infrared contrast agents for image guided surgery
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The success of near-infrared (NIR) fluorescence to be employed for intraoperative imaging relies on the ability to develop a highly stable, NIR fluorescent, nontoxic, biocompatible, and highly excreted compound that retains a reactive functionality for co
- Njiojob, Costyl N.,Owens, Eric A.,Narayana, Lakshminarayana,Hyun, Hoon,Choi, Hak Soo,Henary, Maged
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p. 2845 - 2854
(2015/04/14)
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- SUBSTITUTED DIAMINOPYRIMIDYL COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH
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Provided herein are diaminopyrimidyl Compounds having the following structures: wherein X, L, R1, and R2 are as defined herein, compositions comprising an effective amount of a Diaminopyrimidyl Compound, and methods for treating or preventing PKC-theta-mediated disorders, or a condition treatable or preventable by inhibition of a kinase, for example, PKC-theta.
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Paragraph 0313
(2015/07/02)
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- Polymer conjugate of folic acid or folic acid derivative
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Disclosed is a polymer conjugate of folic acid or a folic acid derivative, wherein an amide bond is not used. The compound has chemical stability and adequate drug release rate in the living organism. Specifically disclosed is a polymer conjugate of folic
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Page/Page column 12
(2015/10/28)
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- Photocatalytic decarboxylative reduction of carboxylic acids and its application in asymmetric synthesis
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The decarboxylative reduction of naturally abundant carboxylic acids such as α-amino acids and α-hydroxy acids has been achieved via visible-light photoredox catalysis. By using an organocatalytic photoredox system, this method offers a mild and rapid entry to a variety of high-value compounds including medicinally relevant scaffolds. Regioselective decarboxylation is achieved when differently substituted dicarboxylic acids are employed. The application of this method to the synthesis of enantioenriched 1-aryl-2,2,2-trifluoroethyl chiral amines starting from natural α-amino acids further testifies to the utility of the developed photocatalytic decarboxylative reduction protocol.
- Cassani, Carlo,Bergonzini, Giulia,Wallentin, Carl-Johan
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supporting information
p. 4228 - 4231
(2014/09/30)
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- A biomimetic catalytic aerobic functionalization of phenols
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The importance of aromatic C-O, C-N, and C-S bonds necessitates increasingly efficient strategies for their formation. Herein, we report a biomimetic approach that converts phenolic C-H bonds into C-O, C-N, and C-S bonds at the sole expense of reducing dioxygen (O2) to water (H 2O). Our method hinges on a regio- and chemoselective copper-catalyzed aerobic oxygenation to provide ortho-quinones. ortho-Quinones are versatile intermediates, whose direct catalytic aerobic synthesis from phenols enables a mild and efficient means of synthesizing polyfunctional aromatic rings. The direct approach: Polyfunctional aromatic rings have been generated by direct functionalization of C-H bonds to C-O, C-N, and C-S bonds at the sole expense of reducing O2 to H2O. The method hinges on a regio- and chemoselective, copper-catalyzed aerobic oxygenation of phenols to provide ortho-quinones (see scheme), thus mimicking the ubiquitous biosynthetic pathway of melanogenesis.
- Esguerra, Kenneth Virgel N.,Fall, Yacoub,Lumb, Jean-Philip
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supporting information
p. 5877 - 5881
(2014/06/10)
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- NEW CYCLOHEXYL AND QUINUCLIDINYL CARBAMATE DERIVATIVES HAVING BETA2 ADRENERGIC AGONIST AND M3 MUSCARINIC ANTAGONIST ACTIVITY
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The present invention relates to novel compounds having β2 adrenergic agonist and M3 muscarinic antagonist dual activity, to pharmaceutical compositions containing them, to the process for their preparation and to their use in respiratory therapies.
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Page/Page column 63; 64
(2014/07/08)
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- Molecular recognition and scavenging of arsenate from aqueous solution using dimetallic receptors
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A series of copper(II), nickel(II) and zinc(II) dimetallic complexes were prepared and their affinities towards arsenate investigated. Indicator displacement assays (IDAs) were carried out to establish the complexes with best affinities towards arsenate.
- Moffat, Chris D.,Weiss, Dominik J.,Shivalingam, Arun,White, Andrew J.P.,Salaun, Pascal,Vilar, Ramon
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supporting information
p. 17168 - 17177
(2015/02/19)
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- Regioselective deiodination of iodothyronamines, endogenous thyroid hormone derivatives, by deiodinase mimics
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Iodothyronine deiodinases (IDs) are mammalian selenoenzymes that play an important role in the activation and inactivation￡ of thyroid hormones. It is known that iodothyronamines (TnAMs), produced by the decarboxylation of thyroid hormones, act as substrates for deiodinases. To understand whether decarboxylation alters the rate and/or regioselectivity of deiodination by using synthetic deiodinase mimics, we studied the deiodination of different iodothyronamines. The triiodo derivative 3,3,5-triiodothyronamine (T3 AM) is deiodinated at the inner ring by naphthyl-based deiodinase mimics, which is similar to the deiodination of 3,3,5-triiodothyronine (T3). However, T3 AM undergoes much slower deiodination than T3. Detailed experimental and theoretical investigations suggest that T3 AM forms a weaker halogen bond with selenium donors than T3. Kinetic studies and single-crystal X-ray structures of T3 and T3 AM reveal that intermolecular I...I interactions may play an important role in deiodination. The formation of hydrogen- and halogen-bonding assemblies, which leads to the formation of a dimeric species of T3 in solution, facilitates the interactions between the selenium and iodine atoms. In contrast, T3 AM, which does not have I...I interactions, undergoes much slower deiodination.
- Mondal, Santanu,Mugesh, Govindasamy
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supporting information
p. 11120 - 11128,9
(2014/11/27)
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- SUBSTITUTED 4-PHENOXYPHENOL ANALOGS AS MODULATORS OF PROLIFERATING CELL NUCLEAR ANTIGEN ACTIVITY
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In one aspect, the invention relates to substituted 4-phenoxyphenol analogs, derivatives thereof, and related compounds,which are useful as inhibitors of proliferating cell nuclear antigen (PCNA); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating hyperproliferative disorders associated with PCNA using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention
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Paragraph 00578; 00579
(2013/03/26)
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- Diverse alkaloid-like structures from a common building block
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A wealth of unique enantiopure polycyclic alkaloid-like scaffolds can be prepared on a multigram scale in only a few steps from a common, commercially available intermediate. The attached nitromethyl group can then be used to construct highly diverse func
- Goff, Dane A.
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p. 242 - 256
(2013/01/15)
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- SYNTHESIS OF POLYCYCLIC ALKALOIDS
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Disclosed embodiments concern polycyclic alkaloid compounds and methods for their use and synthesis. Particular embodiments concern polycyclic alkaloids having a fused, six-membered ring, while other embodiments concern polycyclic alkaloids having a fused
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Paragraph 0224
(2013/09/26)
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- Hybrid ligand-alkylating agents targeting telomeric G-quadruplex structures
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The synthesis, physico-chemical properties and biological effects of a new class of naphthalene diimides (NDIs) capable of reversibly binding telomeric DNA and alkylate it through an electrophilic quinone methide moiety (QM), are reported. FRET and circular dichroism assays showed a marked stabilization and selectivity towards telomeric G4 DNA folded in a hybrid topology. NDI-QMs' alkylating properties revealed a good reactivity on single nucleosides and selectivity towards telomeric G4. A selected NDI was able to significantly impair the growth of melanoma cells by causing telomere dysfunction and down-regulation of telomerase expression. These findings points to our hybrid ligand-alkylating NDIs as possible tools for the development of novel targeted anticancer therapies.
- Doria, Filippo,Germani, Luca,Percivalle, Claudia,Freccero, Mauro,Nadai, Matteo,Richter, Sara N.,Folini, Marco,Zaffaroni, Nadia,Di Antonio, Marco,Sissi, Claudia,Alcaro, Stefano,Artese, Anna
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supporting information
p. 2798 - 2806,9
(2020/08/31)
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- Sticky nanoparticles: A platform for siRNA delivery by a bis(zinc(II) dipicolylamine)-functionalized, self-assembled nanoconjugate
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Delivering the goods: Multifunctional, self-assembled, polymeric nanoparticles for the simultaneous delivery of small-molecule drugs and siRNA have been synthesized. The nanoparticles are composed of biodegradable hyaluronic acid, for tumor targeting and
- Liu, Gang,Choi, Ki Young,Bhirde, Ashwinkumar,Swierczewska, Magdalena,Yin, Juan,Lee, Sang Wook,Park, Jae Hyung,Hong, Jong In,Xie, Jin,Niu, Gang,Kiesewetter, Dale O.,Lee, Seulki,Chen, Xiaoyuan
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supporting information; scheme or table
p. 445 - 449
(2012/02/04)
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- QUATERNARY AMMONIUM SALT COMPOUNDS
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[Problem] The object of the present invention is to provide a novel compound having 132 adrenergic receptor agonist activity and muscarinic receptor antagonist activity. [Means for Solving the Problem] The present invention is a quaternary ammonium salt compounds represented by formula (I), or a pharmaceutically acceptable salt thereof, with superior β32 adrenergic receptor agonist activity and muscarinic receptor antagonist activity.
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Page/Page column 60; 61
(2012/03/10)
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