- Novel analogs of PSNCBAM-1 as allosteric modulators of cannabinoid CB1 receptor
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In this work, we explored the molecular framework of the known CB1R allosteric modulator PSNCBAM-1 with the aim to generate new bioactive analogs and to deepen the structure-activity relationships of this type of compounds. In particular, the introduction
- Bertini, Simone,Chicca, Andrea,Gado, Francesca,Arena, Chiara,Nieri, Daniela,Digiacomo, Maria,Saccomanni, Giuseppe,Zhao, Pingwei,Abood, Mary E.,Macchia, Marco,Gertsch, Jürg,Manera, Clementina
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- Transition Metal-Free Synthesis of meta-Bromo- and meta-Trifluoromethylanilines from Cyclopentanones by a Cascade Reaction
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Anilines are key constituents in biologically active compounds and often obtained from transition metal-catalyzed coupling of an aryl halide with an amine. In this work, we report a transition metal-free method for the synthesis of meta-bromo- and meta-trifluoromethylanilines starting from 3-tribromomethylcyclopentanone or 3-(2-bromo-2-chloro-1,1,1-trifluoroethyl)cyclopentanone, respectively. The scope of the transformation is shown by application of primary, secondary and aromatic amines. The reaction proceeds in acceptable to high yields (20–81 %), and allows for the synthesis of anilines with substitution patterns otherwise difficult to access.
- Bunch, Lennart,Cetin, Adnan,Staudt, Markus
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supporting information
(2022/02/10)
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- Silicon-based rhodamine fluorescent staining reagent as well as preparation method and application thereof
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The invention discloses a silicon-based rhodamine fluorescent staining reagent as well as a preparation method and application thereof, and belongs to the field of organic chemistry and biochemistry.According to the silicon-based rhodamine fluorescent staining reagent as well as preparation method and application thereof of the invention, a silicon atom substituted rhodamine derivative is used asa basic frame, and is modified with aromatic amines in different forms, so that the silicon-based rhodamine fluorescent staining reagent which has large Stokes shift and high fluorescence intensity and can mark immunoglobulin IgG can be synthesized, so that the silicon-based rhodamine fluorescent staining reagent can be used for in-vitro SARS-CoV2-virus specific antibody fluorescence ELISA detection. The silicon-based rhodamine fluorescence staining reagent has large Stokes shift (greater than 140 nm), can effectively avoid mutual interference of excitation light and emitted light, and is high in detection sensitivity; a fluorescence ELISA detection method established based on the fluorescence antibody can be suitable for microplate readers with different bandwidths, and is wide in application range.
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Paragraph 0105-0110
(2021/01/29)
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- Lysosome targeted staining reagent based on carbon atom rhodamine derivative skeleton as well as preparation method and application of lysosome targeted staining reagent
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The invention discloses a lysosome targeted staining reagent based on a carbon atom rhodamine derivative skeleton and a preparation method and application of the lysosome targeted staining reagent. According to the lysosome targeted staining reagent, the carbon atom substituted amino rhodamine derivative skeleton is used as the basis of lysosome dye, and through reasonable regulation and control and design of different forms of aromatic amines, the lysosome targeted staining reagent with different emission wavelengths based on the carbon atom rhodamine derivative skeleton is obtained by usingthe carbon atom rhodamine derivative skeleton as a raw material, can realize ultralow-concentration targeted imaging while realizing rapid targeted staining, has high biocompatibility, and does not interfere with the physiological activity of living cells. Besides, the staining reagent has the characteristic of ultra-large Stokes shift, so that imaging interference caused by scattered light of exciting light is basically avoided during biological imaging, and the dye also has specific performance of high signal-to-noise ratio imaging. The preparation method disclosed by the invention is high in yield and mild in reaction condition, and the prepared staining reagent is large in Stokes shift and high in targeting property.
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Paragraph 0047; 0081-0086
(2021/03/18)
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- PSNCBAM-1 analogs: Structural evolutions and allosteric properties at cannabinoid CB1 receptor
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Allosteric modulation of the CB1Rs could represent an alternative strategy for the treatment of diseases in which these receptors are involved, without the undesirable effects associated with their orthosteric stimulation. PSNCBAM-1 is a reference diaryl urea derivative that positively affects the binding affinity of orthosteric ligands (PAM) and negatively affects the functional activity of orthosteric ligands (NAM) at CB1Rs. In this work we reported the design, synthesis and biological evaluation of three different series of compounds, derived from structural modifications of PSNCBAM-1 and its analogs reported in the recent literature. Almost all the new compounds increased the percentage of binding affinity of CP55940 at CB1Rs, showing a PAM profile. When tested alone in the [35S]GTPγS functional assay, only a few derivatives lacked detectable activity, so were tested in the same functional assay in the presence of CP55940. Among these, compounds 11 and 18 proved to be functional NAMs at CB1Rs, dampening the orthosteric agonist-induced receptor functionality by approximately 30percent. The structural features presented in this work provide new CB1R-allosteric modulators (with a profile similar to the reference compound PSNCBAM-1) and an extension of the structure-activity relationships for this type of molecule at CB1Rs.
- Meini, Serena,Gado, Francesca,Stevenson, Lesley A.,Digiacomo, Maria,Saba, Alessandro,Codini, Simone,Macchia, Marco,Pertwee, Roger G.,Bertini, Simone,Manera, Clementina
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- Synthesis of unsymmetrical Si-rhodamine fluorophores and application to a far-red to near-infrared fluorescence probe for hypoxia
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Si-Rhodamines are bright fluorophores with red to near-infrared (NIR) emission, and are widely used for fluorescence imaging of biological phenomena. Here, in order to extend the scope of Si-rhodamine fluorophores, we established a versatile synthesis of unsymmetrical Si-rhodamines. To illustrate its value, we used one of these new fluorophores to synthesize a far-red to NIR fluorescence probe for hypoxia, and showed that it can visualize hepatic ischemia in mice in vivo.
- Hanaoka, Kenjiro,Kagami, Yu,Piao, Wen,Myochin, Takuya,Numasawa, Koji,Kuriki, Yugo,Ikeno, Takayuki,Ueno, Tasuku,Komatsu, Toru,Terai, Takuya,Nagano, Tetsuo,Urano, Yasuteru
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supporting information
p. 6939 - 6942
(2018/06/26)
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- Transition-Metal-Free Selective C?H Benzylation of Tertiary Arylamines by a Dearomatization-Aromatization Sequence
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Due to the significance of hybrid systems in drug discovery, there is an urgent need to assemble multiple biologically active ingredients into a single molecule. Here, we report a general transition-metal-free selective C?H benzylation of tertiary arylamines in good to excellent yields with a broad substrate scope and high functional-group tolerance under mild conditions. Besides arylamines, some other benzene derivatives also readily furnished the corresponding diaryl methane derivatives with this protocol. A series of control experiments and theoretical calculations indicated that this transition-metal-free reaction is a dearomatization-aromatization process.
- Xu, Guo-Qiang,Feng, Zhi-Tao,Xu, Ji-Tao,Wang, Zhu-Yin,Qin, Yong,Xu, Peng-Fei
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supporting information
p. 13778 - 13782
(2018/09/14)
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- BIARYL DERIVATIVE AS GPR120 AGONIST
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The present invention relates to a biaryl derivative expressed by the chemical formula 1, a method for producing the biaryl derivative, a pharmaceutical composition comprising same, and use of same, the biaryl derivative expressed by the chemical formula 1, as a GPR120 agonist, promoting GLP-1 generation in the gastro-intestinal tract, reducing insulin resistance in the liver, muscles and the like from anti-inflammatory activity in the macrophage, pancreatic cells and the like, and allowing effective use in prevention or treatment of inflammation or metabolic diseases such as diabetes, complications from diabetes, obesity, non-alcoholic fatty liver disease, fatty liver disease, and osteoporosis.
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Paragraph 0165
(2017/11/17)
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- ALLOSTERIC MODULATORS OF THE CANNIBINOID 1 RECEPTOR
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The present technology relates to compounds and compositions of Formulas I, II, VII, and VIII, and methods using such compounds. The compounds and compositions described herein may be used in the treatment or prophylaxis of addiction, metabolic syndrome, obesity, and/or a CB1 receptor-medited disorder.
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Paragraph 0247
(2015/03/13)
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- Catalytic Asymmetric Arylation of α-Aryl-α-diazoacetates with Aniline Derivatives
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The asymmetric arylation of diazo compounds with aniline derivatives cooperatively catalyzed by an achiral dirhodium complex and a chiral spiro phosphoric acid is reported. The reaction provides a new method for the facile synthesis of α-diarylacetates, v
- Xu, Bin,Li, Mao-Lin,Zuo, Xiao-Dong,Zhu, Shou-Fei,Zhou, Qi-Lin
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supporting information
p. 8700 - 8703
(2015/07/27)
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- N-heterocyclization of primary amines with dihalides using microreactors
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(Chemical Equation Presented) A practical, rapid, and efficient reaction using microreactors for the direct N-alkylation from aniline derivatives and alkyl dihalides has been achieved in the presence of aqueous potassium carbonate at an elevated temperature. This improved synthetic methodology provides a straightforward microfluid approach to the synthesis of a variety of N-aryl azacycloalkanes. Copyright Taylor & Francis Group, LLC.
- He, Hongjie,Lin, Qi,Liu, Xiaofeng,Yang, Yongtai,Zhou, Yaming,Jia, Yu,Gao, Xiang
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experimental part
p. 2512 - 2525
(2012/07/14)
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- Palladium-catalyzed monoamination of dihalogenated benzenes
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The palladium-catalyzed monoamination of symmetric dibromobenzenes can be performed using a catalyst based on Pd2dba3 and BINAP in the presence of NaO(t-Bu). The analogous transformation of non-symmetric bromoiodobenzenes is most effectively performed with Xantphos as the ligand, while reactions with BINAP were non-selective. These transformations can be scaled uneventfully to >10 g quantities. They do not require drybox or Schlenk techniques, and all reagents are weighed out in air. The resulting monobromoanilines are versatile intermediates for further synthetic transformations.
- Larsen, Simon Birks?,Bang-Andersen, Benny,Johansen, Tommy N?rskov,J?rgensen, Morten
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p. 2938 - 2950
(2008/09/19)
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- 4' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1, R2, R5, R6, B, D, E, G, Q, x and n are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 44
(2009/01/24)
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- 6' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1—R4 A, B, D, E, and G are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 66
(2008/12/08)
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- Reductive one batch synthesis of N-substituted pyrrolidines from primary amines and 2,5-dimethoxytetrahydrofuran
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The construction of the pyrrolidine ring about a nitrogen of a primary amine by a reductive condensation reaction using 2,5- dimethoxytetrahydrofuran and sodium borohydride in acidic water medium is described. The reaction is fast, affords good to excellent yields and appears insensitive to electron effects and severe steric hindrance; it is found to be compatible with a large variety of aryl substituents, including nitro and oxo groups. The reaction allows the introduction of two deuterium atoms, with label conservation, in both the α-positions of the pyrrolidine ring by the use of sodium borodeuteride instead of sodium borohydride.
- Verardo, Giancarlo,Dolce, Anna,Toniutti, Nicoletta
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