- A “universal” catalyst for aerobic oxidations to synthesize (hetero)aromatic aldehydes, ketones, esters, acids, nitriles, and amides
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Functionalized (hetero)aromatic compounds are indispensable chemicals widely used in basic and applied sciences. Among these, especially aromatic aldehydes, ketones, carboxylic acids, esters, nitriles, and amides represent valuable fine and bulk chemicals, which are used in chemical, pharmaceutical, agrochemical, and material industries. For their synthesis, catalytic aerobic oxidation of alcohols constitutes a green, sustainable, and cost-effective process, which should ideally make use of active and selective 3D metals. Here, we report the preparation of graphitic layers encapsulated in Co-nanoparticles by pyrolysis of cobalt-piperazine-tartaric acid complex on carbon as a most general oxidation catalyst. This unique material allows for the synthesis of simple, functionalized, and structurally diverse (hetero)aromatic aldehydes, ketones, carboxylic acids, esters, nitriles, and amides from alcohols in excellent yields in the presence of air.
- Bartling, Stephan,Beller, Matthias,Chandrashekhar, Vishwas G.,Jagadeesh, Rajenahally V.,Rabeah, Jabor,Rockstroh, Nils,Senthamarai, Thirusangumurugan
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supporting information
p. 508 - 531
(2022/02/11)
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- AUTOMATED DIAZOMETHANE GENERATOR, REACTOR AND SOLID PHASE QUENCHER
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An automated apparatus (Diazo-M-pen and Diazo-M-cube) for production, utilization and quenching of highly toxic diazomethane comprising of integrated pumps, tubular flow reactor, liquid-liquid micro-separator, solid MOF quencher etc.
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Page/Page column 14-16
(2022/03/09)
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- Multichiral liquid crystals based on terphenyl core laterally substituted by chlorine atom
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We designed a new type of antiferroelectric liquid crystalline structure with versatile properties. For this purpose, we modified the previously studied liquid crystalline compounds based on terphenyl molecular core laterally substituted with a chlorine atom. Two lactate units were attached to the chiral chain with the aim to support antiferroelectric structures. We studied the mesomorphic properties of new compounds by means of texture observations under a polarised light microscope, by dielectric spectroscopy and electro-optical measurements. To confirm the phase identification, x-ray measurements were performed. We found that the studied compounds revealed a SmA*-SmC* phase sequence in a broad temperature range. We proved an antiferroelectric phase with orthoconic properties for selected structural modifications. Such valuable optical properties with the tilt angle about 45° promise a big potential for applications.
- Cigl, Martin,Hamplová, Věra,Novotná, Vladimíra,Pociecha, Damian,Podoliak, Natalia
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- Cannabidiol derivative, preparation method and application thereof
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The invention discloses a cannabidiol derivative, a preparation method and application thereof, and belongs to the technical field of medicinal chemistry, wherein the cannabidiol derivative is obtained by taking cannabidiol as a main body through a synthesis means, and an anti-tumor activity determination result shows that the cannabidiol derivative prepared by the invention has an inhibition effect on lung cancer cell strains, human breast cancer cell strains, nasopharynx cancer and drug-resistant strains thereof.
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Paragraph 0027; 0035; 0038
(2021/07/28)
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- Design and biological evaluation of phenyl imidazole analogs as hedgehog signaling pathway inhibitors
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The hedgehog (Hh) signaling pathway is involved in diverse aspects of cellular events. Aberrant activation of Hh signaling pathway drives oncogenic transformation for a wide range of cancers, and it is therefore a promising target in cancer therapy. In the principle of association and ring-opening, we designed and synthesized a series of Hh signaling pathway inhibitors with phenyl imidazole scaffold, which were biologically evaluated in Gli-Luc reporter assay. Compound 25 was identified to possess high potency with nanomolar IC50, and moreover, it preserved the inhibition against wild-type and drug-resistant Smo-overexpressing cells. A molecular modeling study of compound 25 expounded its binding mode to Smo receptor, providing a basis for the further structural modification of phenyl imidazole analogs.
- Sun, Chiyu,Zhang, Ying,Wang, Han,Yin, Zhengxu,Wu, Lingqiong,Huang, Yanmiao,Zhang, Wenhu,Wang, Youbing,Hu, Qibo
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p. 546 - 552
(2020/10/06)
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- Enabling Metallophotoredox Catalysis in Parallel Solution-Phase Synthesis Using Disintegrating Reagent Tablets
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Compressed tablets containing a mixture of a photocatalyst, a nickel catalyst, an inorganic base, and an inert excipient are employed as a fast, safe, and user-friendly chemical delivery system for two different metallophotoredox-catalyzed reactions. This delivery method simplifies the preparation of compound libraries using photoredox chemistry in a parallel setting. The reagent tablets were successfully applied to late-stage functionalization of drug-like intermediates. These tablets can be prepared with various reagents and catalysts in different sizes and be stored on the bench thanks to blister packaging.
- Borlinghaus, Niginia,Sch?nfeld, Barbara,Heitz, Stephanie,Klee, Johanna,Vukeli?, Stella,Braje, Wilfried M.,Jolit, Anais
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p. 16535 - 16547
(2021/12/02)
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- Electro-Oxidative Selective Esterification of Methylarenes and Benzaldehydes
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A mild and green electro-oxidative protocol to construct aromatic esters from methylarenes and alcohols is herein reported. Importantly, the reaction is free of metals, chemical oxidants, bases, acids, and operates at room temperature. Moreover, the design of the electrolyte was found critical for the oxidation state and structure of the coupling products, a rarely documented effect. This electro-oxidative coupling process also displays exceptional tolerance of many fragile easily oxidized functional groups such as hydroxy, aldehyde, olefin, alkyne, as well as neighboring benzylic positions. The enantiomeric enrichment of some chiral alcohols is moreover preserved during this electro-oxidative coupling reaction, making it overall a promising synthetic tool.
- Yu, Congjun,?zkaya, Bünyamin,Patureau, Frederic W.
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supporting information
p. 3682 - 3687
(2021/02/01)
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- Photoconductive bent-core liquid crystalline radicals with a paramagnetic polar switchable phase
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A series of self-organizing bent-core derivatives 1[12,n], containing a highly π-delocalized stable radical as the central angular structural element, is described. The planarity of the open-shell core permits efficient π-π stacking, which results in the formation of B2 and soft crystalline phases above 100 °C. Optical, XRD and dielectric analyses of 1[12,12] indicate that the ground state of the observed B2 phase is polar antiferroelectric of type SmCAPA exhibiting tristable electro-optical switching. SQUID and EPR measurements revealed strong antiferromagnetic spin-spin exchange interactions below the isotropic phase, which have been estimated at θ = -46 cm-1 with the Curie-Weiss law. Transient photoconductivity was observed in the B2 phase with a hole carrier mobility μh of 1.4 × 10-4 cm2 V-1 s-1
- Shivakumar, Kilingaru I.,Pociecha, Damian,Szczytko, Jacek,Kapu?ciński, Szymon,Monobe, Hirosato,Kaszyński, Piotr
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supporting information
p. 1083 - 1088
(2020/02/05)
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- Palladium-Catalyzed Chlorocarbonylation of Aryl (Pseudo)Halides Through In Situ Generation of Carbon Monoxide
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An efficient palladium-catalyzed chlorocarbonylation of aryl (pseudo)halides that gives access to a wide range of carboxylic acid derivatives has been developed. The use of butyryl chloride as a combined CO and Cl source eludes the need for toxic, gaseous carbon monoxide, thus facilitating the synthesis of high-value products from readily available aryl (pseudo)halides. The combination of palladium(0), Xantphos, and an amine base is essential to promote this broadly applicable catalytic reaction. Overall, this reaction provides access to a great variety of carbonyl-containing products through in situ transformation of the generated aroyl chloride. Combined experimental and computational studies support a reaction mechanism involving in situ generation of CO.
- Bismuto, Alessandro,Boehm, Philip,Morandi, Bill,Roediger, Sven
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supporting information
p. 17887 - 17896
(2020/08/19)
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- Construction of C–O bond via cross-dehydrogenative coupling of sp [ 3] C–H bond with phenols catalyzed by copper porphyrin
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Copper porphyrin-catalyzed construction of ether bond by cross-dehydrogenative coupling of sp [3] C–H bond with phenols bearing electron-withdrawing groups (EWG) was described for the first time. A broad range of substrates afforded different acetals in m
- Yang, Shuang,Xiong, Ming-Feng,Tian, Wan-Qun,Zhang, Hao,Xiao, Xin-Yan,Liu, Hai-Yang,Chang, Chi-Kwong
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- Methoxylation of Acyl Fluorides with Tris(2,4,6-trimethoxyphenyl)phosphine via C-OMe Bond Cleavage under Metal-Free Conditions
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Acyl fluorides are subjected to methoxylation with tris(2,4,6-trimethoxyphenyl)phosphine (TMPP) to afford the corresponding methyl esters in good to excellent yields. This transformation is featured by C(sp2)-OMe bond cleavage under metal-free conditions. Unprecedented utilization of TMPP as a methoxylating agent realized the installation of an OMe group into the desired products.
- Ishida, Takumi,Nishihara, Yasushi,Wang, Xiu,Wang, Zhenhua
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p. 7526 - 7533
(2020/06/27)
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- Design of Hydrazide-Bearing HDACIs Based on Panobinostat and Their p53 and FLT3-ITD Dependency in Antileukemia Activity
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Here, we present a new series of hydrazide-bearing class I selective HDAC inhibitors designed based on panobinostat. The cap, linker, and zinc-binding group were derivatized to improve HDAC affinity and antileukemia efficacy. Lead inhibitor 13a shows picomolar or low nanomolar IC50 values against HDAC1 and HDAC3 and exhibits differential toxicity profiles toward multiple cancer cells with different FLT3 and p53 statuses. 13a indirectly inhibits the FLT3 signaling pathway and down-regulates master antiapoptotic proteins, resulting in the activation of pro-caspase3 in wt-p53 FLT3-ITD MV4-11 cells. While in the wt-FLT3 and p53-null cells, 13a is incapable of causing apoptosis at a therapeutic concentration. The MDM2 antagonist and the proteasome inhibitor promote 13a-triggered apoptosis by preventing p53 degradation. Furthermore, we demonstrate that apoptosis rather than autophagy is the key contributing factor for 13a-triggered cell death. When compared to panobinostat, 13a is not mutagenic and displays superior in vivo bioavailability and a higher AUC0-inf value.
- Li, Xiaoyang,Jiang, Yuqi,Peterson, Yuri K.,Xu, Tongqiang,Himes, Richard A.,Luo, Xin,Yin, Guilin,Inks, Elizabeth S.,Dolloff, Nathan,Halene, Stephanie,Chan, Sherine S. L.,Chou, C. James
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p. 5501 - 5525
(2020/06/10)
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- Synthesis and comparative structure-activity study of carbohydrate-based phenolic compounds as α-glucosidase inhibitors and antioxidants
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Twenty-one natural and unnatural phenolic compounds containing a carbohydrate moiety were synthesized and their structure-activity relationship (SAR) was evaluated for α-glucosidase inhibition and antioxidative activity. Varying the position of the galloyl unit on the 1,5-anhydro -D-glucitol (1,5-AG) core resulted in changes in the α-glucosidase inhibitory activity and notably, particularly strong activity was demonstrated when the galloyl unit was present at the C-2 position. Furthermore, increasing the number of the galloyl units significantly affected the α-glucosidase inhibition, and 2,3,4,6-tetra-galloyl-1,5-AG (54) and 2,3,4,6-tetra-galloyl-d-glucopyranose (61) exhibited excellent activities, which were more than 13-fold higher than the α-glucosidase inhibitory activity of acertannin (37). Moreover, a comparative structure-activity study suggested that a hemiacetal hydroxyl functionality in the carbohydrate core and a biaryl bond of the 4,6-O-hexahydroxydiphenoyl (HHDP) group, which are components of ellagitannins including tellimagrandin I, are not necessary for the α-glucosidase inhibitory activity. Lastly, the antioxidant activity increased proportionally with the number of galloyl units.
- MacHida, Shota,Mukai, Saki,Kono, Rina,Funato, Megumi,Saito, Hiroaki,Uchiyama, Taketo
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- BENZOTHIAZOLE AND PYRIDOTHIAZOLE COMPOUNDS AS SUMO ACTIVATORS
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Provided are SUMO activators, which can enhance SUMOylation of SERCA2a, which are useful in the treatment of heart failure, cardiovascular diseases, cancer, neurodegenerative disorders, viral infection, bacterial infection, liver disease, inflammation, and other diseases.
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Page/Page column 30
(2019/02/06)
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- Synthesis, structure activity relationship and in vitro anti-influenza virus activity of novel polyphenol-pentacyclic triterpene conjugates
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It is urgently necessary to develop more effective anti-influenza agents due to the continuous emergence of drug-resistant strains of influenza virus. Our earlier studies have identified that certain pentacyclic triterpene derivatives are effective inhibitors of influenza virus infection. In the present study, a series of C-28 modified pentacyclic triterpene derivatives via conjugation with a series of polyphenols were synthesized, and their antiviral activities against influenza A/WSN/33 (H1N1) virus in MDCK (Madin-Darby canine kidney) cells were evaluated. Four compounds 23m, 23o, 23q and 23s displayed robust anti-influenza potency with averaged IC50 values at the low-micromole level, surpassing the potency of oseltamivir. In addition, the in vitro cytotoxic activity of the four conjugates against MDCK cells showed no toxicity at 100 μM. Further mechanism studies of compound 23s, one of the best representative conjugates with IC50 value of 5.80 μM and a selective index (SI) value of over 17.2, by hemagglutination inhibition (HI), surface plasmon resonance and molecular modeling indicated that this conjugate bound tightly to the viral envelope hemagglutinin (KD = 15.6 μM), thus blocking the invasion of influenza viruses into host cells.
- Li, Haiwei,Li, Man,Xu, Renyang,Wang, Shouxin,Zhang, Yongmin,Zhang, Lihe,Zhou, Demin,Xiao, Sulong
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p. 560 - 568
(2019/01/03)
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- Identification of new aryl hydrocarbon receptor (AhR) antagonists using a zebrafish model
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A new series of 1,3-diketone, heterocyclic and α,β-unsaturated derivatives were synthesized and evaluated for their AhR antagonist activity using zebrafish and mammalian cells. Compounds 1b, 2c, 3b and 5b showed significant AhR antagonist activity in a transgenic zebrafish model. Among them, compound 3b, and 5b were found to have excellent AhR antagonist activity with IC50 of 3.36 nM and 8.3 nM in a luciferase reporter gene assay. In stem cell proliferation assay, compound 5b elicited marked HSC expansion.
- Jeong, Jieun,Kim, Kun-Hee,Kim, Dong-Young,Chandrasekaran, Gopalakrishnan,Kim, Minhee,Pagire, Suvarna H.,Dighe, Mahesh,Choi, Eun Young,Bak, Su-Min,Kim, Eun-Young,Shin, Myung-Geun,Choi, Seok-Yong,Ahn, Jin Hee
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- Semiheterogeneous Dual Nickel/Photocatalytic (Thio)etherification Using Carbon Nitrides
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A carbon nitride material can be combined with homogeneous nickel catalysts for light-mediated cross-couplings of aryl bromides with alcohols under mild conditions. The metal-free heterogeneous semiconductor is fully recyclable and couples a broad range of electron-poor aryl bromides with primary and secondary alcohols as well as water. The application for intramolecular reactions and the synthesis of active pharmaceutical ingredients was demonstrated. The catalytic protocol is applicable for the coupling of aryl iodides with thiols as well.
- Cavedon, Cristian,Madani, Amiera,Seeberger, Peter H.,Pieber, Bartholom?us
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supporting information
p. 5331 - 5334
(2019/07/08)
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- Ultrasound assisted synthesis of 4-(Benzyloxy)-N-(3-chloro-2-(substitutedphenyl)-4-oxoazetidin-1-yl) benzamide as challenging anti-tubercular scaffold
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A series of ten novel derivatives of 4-(benzyloxy)-N-(3-chloro-2-(substituted phenyl)-4-oxoazetidin-1-yl) benzamide 6a–j were synthesized in good yield from the key compound 4-(benzyloxy)-N’-(substituted benzylidene) benzo hydrazide, called Schiff’s bases 5a–j, by Staudinger reaction ([2 + 2] ketene-imine cycloaddition reaction) with chloro acetyl chloride in the presence of catalyst tri ethylamine and solvent dimethyl formamide (DMF), by using ultra-sonication as one of the green chemistry tools. All the synthesised compounds were evaluated for in vitro anti-tubercular activity against Mycobacterium tuberculosis (MTB) and most of them showed promising activity with an IC50 value of less than 1 μg/mL. To establish the safety, all the synthesized compounds were further tested for cytotoxicity against the human cancer cell line HeLa and all 6a–j compounds were found to be non-cytotoxic in nature. The molecular docking study was carried out with essential enzyme InhA (FabI/ENR) of Mycobacterium responsible for cell wall synthesis which suggests that 6a and 6e are the most active derivatives of the series. The theoretical evaluation of cell permeability based on Lipinski’s rule of five has helped to rationalize the biological results and hence the synthesized azetidinone derivatives 6a–j were also analyzed for physicochemical evaluation that is, absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties and the results showed that all the derivatives could comply with essential features required for a potential lead in the anti-tubercular drug discovery process.
- Nimbalkar, Urja D.,Seijas, Julio A.,Borkute, Rachna,Damale, Manoj G.,Sangshetti, Jaiprakash N.,Sarkar, Dhiman,Nikalje, Anna Pratima G.
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- 1-substituted benzoyl-4-fatty acyl semicarbazide derivative, preparation method and application thereof as antibacterial agent
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The invention belongs to the technical field of antibacterial agents, and relates to a 1-substituted benzoyl-4-fatty acyl semicarbazide derivative, a preparation method and application thereof as an antibacterial agent. The compound is shown in a formula
- -
-
Paragraph 0273-0275
(2018/09/14)
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- COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF BROMODOMAIN-CONTAINING PROTEINS
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The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.
- -
-
Paragraph 00228
(2017/03/21)
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- Bent-core mesogens with an aromatic unit at the terminal position
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Bent-core liquid crystals with a naphthalene central unit and an aromatic ring at the terminal position of molecular tails were synthesised with the aim of enhancing nanosegregation. It was found that the length of the spacer between the rigid core and the terminal aromatic moiety had a profound influence on the liquid crystal polymorphism. The homologues with short spacers exhibited nematic and columnar phases, whereas the homologue with long spacers exhibited a tilted lamellar phase with a liquid-like in-plane order, indicating an unusual morphology of the densely packed toroidal objects. The morphology can be changed to twisted ribbons by small additives adsorbed on the membrane surface. This is the first example of twisted ribbons constructed by a lamellar system with no long-range in-plane order.
- Bajzíková, Kvetoslava,Svoboda, Ji?í,Novotná, Vladimíra,Pociecha, Damian,Gorecka, Ewa
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supporting information
p. 4672 - 4679
(2017/07/10)
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- Ultrasound- and molecular sieves-assisted synthesis, molecular docking and antifungal evaluation of 5-(4-(benzyloxy)-substituted phenyl)-3-((phenylamino)methyl)-1,3,4-oxadiazole-2(3h)-thiones
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A novel series of 5-(4-(benzyloxy)substituted phenyl)-3-((phenyl amino)methyl)-1,3,4-oxadiazole-2(3H)-thione Mannich bases 6a-o were synthesized in good yield from the key compound 5-(4-(benzyloxy)phenyl)-1,3,4-oxadiazole-2(3H)-thione by aminomethylation with paraformaldehyde and substituted amines using molecular sieves and sonication as green chemistry tools. The antifungal activity of the new products was evaluated against seven human pathogenic fungal strains, namely, Candida albicans ATCC 24433, Candida albicans ATCC 10231, Candida glabrata NCYC 388, Cryptococcus neoformans ATCC 34664, Cryptococcus neoformans PRL 518, Aspergillus fumigatus NCIM 902 and Aspergillus niger ATCC 10578. The synthesized compounds 6d, 6f, 6g, 6h and 6j exhibited promising antifungal activity against the tested fungal pathogens. In molecular docking studies, derivatives 6c, 6f and 6i showed good binding at the active site of C. albicans cytochrome P450 enzyme lanosterol 14 α-demethylase. The in vitro antifungal activity results and docking studies indicated that the synthesized compounds have potential antifungal activity and can be further optimized as privileged scaffolds to design and develop potent antifungal drugs.
- Nimbalkar, Urja D.,Tupe, Santosh G.,Vazquez, Julio A. Seijas,Khan, Firoz A. Kalam,Sangshetti, Jaiprakash N.,Nikalje, Anna Pratima G.
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- Benzoic hydroxamate-based iron complexes as model compounds for humic substances: Synthesis, characterization and algal growth experiments
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A series of monomeric and dimeric FeIII complexes bearing benzoic hydroxamates as O,O-chelates has been prepared and characterized by elemental analysis, IR spectroscopy, UV-Vis spectroscopy, electrospray ionization mass spectrometry (ESI-MS), cyclic voltammetry, EPR spectroscopy and for some examples by X-ray diffraction analysis. The stability of the synthesized complexes in pure water and seawater was monitored over 24 h by means of UV-Vis spectrometry. The ability to release iron from the synthesized model complexes has been investigated with algae growth experiments.
- Orlowska, Ewelina,Roller, Alexander,Wiesinger, Hubert,Pignitter, Marc,Jirsa, Franz,Krachler, Regina,Kandioller, Wolfgang,Keppler, Bernhard K.
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p. 40238 - 40249
(2016/05/24)
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- Discovery of Potent and Selective RSK Inhibitors as Biological Probes
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While the p90 ribosomal S6 kinase (RSK) family has been implicated in multiple tumor cell functions, the full understanding of this kinase family has been restricted by the lack of highly selective inhibitors. A bis-phenol pyrazole was identified from hig
- Jain, Rama,Mathur, Michelle,Lan, Jiong,Costales, Abran,Atallah, Gordana,Ramurthy, Savithri,Subramanian, Sharadha,Setti, Lina,Feucht, Paul,Warne, Bob,Doyle, Laura,Basham, Stephen,Jefferson, Anne B.,Lindvall, Mika,Appleton, Brent A.,Shafer, Cynthia M.
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p. 6766 - 6783
(2015/09/22)
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- Modulators of methyl modifying enzymes, compositions and uses thereof
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Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
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Page/Page column 118
(2015/12/26)
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- Synthesis and evaluation of novel N-3-benzimidazolephenylbisamide derivatives for antiproliferative and Hedgehog pathway inhibitory activity
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A series of novel N-3-benzimidazolephenylbisamide derivatives bearing the 4-benzyloxyphenyl moiety were synthesized and evaluated for their antiproliferative activity against MGC803, HT29, MKN45 and SW620 cancer cell lines in vitro. The pharmacological data demonstrated that the majority of the target compounds exhibited higher efficacy against MGC803, HT29 and MKN45 cells, among which compound 7m displayed higher antiproliferative activity than vismodegib. Furthermore, compound 7m manifested better inhibition of the Hedgehog (Hh) signaling pathway in different Hh-related assays and may compete with boron-dipyrromethene (BODIPY)-cyclopamine for binding to the human smoothened (Smo) receptor. In addition, molecular docking studies suggested that compound 7m interacts very closely with the vismodegib docking pose through hydrogen bonds at the taladegib binding site of the Smo receptor.
- Sun, Chiyu,Li, Yangsheng,Shi, Ailong,Zhang, Jingzhou,Li, Yafei,Zhao, Mingming,Zhang, Lijuan,Zheng, Huachuan,Meng, Ying,Ding, Huaiwei,Song, Hongrui
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supporting information
p. 1137 - 1142
(2015/06/25)
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- Synthesis and antifungal activity of 1-aminomethyl-3-{4- (chlorobenzyloxy) benzoylhydrazono}-4, 5/5, 6-dichloroindolin-2- ones
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3-{4-(Chlorobenzyloxy) benzoylhydrazono}-4,5/5,6-dichloroindolin-2-ones 1a,b-5a,b, were synthesized by the condensation of 4-(chlorobenzyloxy) benzoylhydrazines and 4, 5/5, 6-dichloroindolin-2,3-diones. Compounds 1a,b-5a,b when subjected to Mannich reaction with secondary heterocyclic amines in the presence of formaldehyde, furnished 1-aminomethyl-3-{4-(chlorobenzyloxy) benzoylhydrazono}-4, 5/5, 6-dichloroindolin-2- ones 6a,b-20a,b. The structures of the compounds have been established by means of spectral (IR and 1H NMR) and elemental analysis. The compounds have been screened for their antifungal potential against human pathogenic fungi.
- Harrison, Darwin Anil,Rastogi, Nisheeth,Rahman, Masihur
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p. 411 - 418
(2019/01/21)
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- Calcium and magnesium chlorides-catalyzed oxidative esterification of aromatic aldehydes
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An interesting procedure for the oxidative esterification of aromatic aldehydes has been developed. By using catalytic amount of CaCl2 or MgCl2, various methyl benzoates were isolated in good yields with hydrogen peroxide as the terminal oxidant.
- Feng, Jian-Bo,Gong, Jin-Long,Li, Qin,Wu, Xiao-Feng
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p. 1657 - 1659
(2014/03/21)
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- Binding of mazindol and analogs to the human serotonin and dopamine transporterss
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ABSTRACT Mazindol has been explored as a possible agent in cocaine addiction pharmacotherapy. The tetracyclic compound inhibits both the dopamine transporter and the serotonin transporter, and simple chemical modifications considerably alter target selectivity. Mazindol, therefore, is an attractive scaffold for both understanding the molecular determinants of serotonin/ dopamine transporter selectivity and for the development of novel drug abuse treatments. Usingmolecularmodeling and pharmacologic profiling of rationally chosen serotonin and dopamine transporter mutants with respect to a series of mazindol analogs has allowed us to determine the orientation of mazindol within the central binding site. We find that mazindol binds in the central substrate binding site, and that the transporter selectivity can be modulated through mutations of a few residues in the binding pocket. Mazindol is most likely to bind as the R-enantiomer. Tyrosines 95 and 175 in the human serotonin transporter and the corresponding phenylalanines 75 and 155 in the human dopamine transporter are the primary determinants of mazindol selectivity. Manipulating the interaction of substituents on the 7-position with the human serotonin transporter Tyr175 versus dopamine transporter Phe155 is found to be a strong tool in tuning the selectivity of mazindol analogs and may be used in future drug design of cocaine abuse pharmacotherapies. Copyright
- Severinsen, Kasper,Koldso, Heidi,Thorup, Katrine Almind Vinberg,Schjoth-Eskesen, Christina,Moller, Pernille Thornild,Wiborg, Ove,Jensen, Henrik Helligso,Sinning, Steffen,Schiott, Birgit
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supporting information
p. 208 - 217
(2014/01/23)
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- Structure-activity relationships for vitamin D3-based aromatic a-ring analogues as hedgehog pathway inhibitors
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A structure-activity relationship study for a series of vitamin D3-based (VD3) analogues that incorporate aromatic A-ring mimics with varying functionality has provided key insight into scaffold features that result in potent, selective Hedgehog (Hh) pathway inhibition. Three analogue subclasses containing (1) a single substitution at the ortho or para position of the aromatic A-ring, (2) a heteroaryl or biaryl moiety, or (3) multiple substituents on the aromatic A-ring were prepared and evaluated. Aromatic A-ring mimics incorporating either single or multiple hydrophilic moieties on a six-membered ring inhibited the Hh pathway in both Hh-dependent mouse embryonic fibroblasts and cultured cancer cells (IC50 values 0.74-10 μM). Preliminary studies were conducted to probe the cellular mechanisms through which VD3 and 5, the most active analogue, inhibit Hh signaling. These studies suggested that the anti-Hh activity of VD3 is primarily attributed to the vitamin D receptor, whereas 5 affects Hh inhibition through a separate mechanism.
- Deberardinis, Albert M.,Madden, Daniel J.,Banerjee, Upasana,Sail, Vibhavari,Raccuia, Daniel S.,De Carlo, Daniel,Lemieux, Steven M.,Meares, Adam,Hadden, M. Kyle
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p. 3724 - 3736
(2014/05/20)
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- Synthesis and mesophase characterization of novel methacrylate based thermotropic liquid crystalline monomers and their polymers
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A new series of side chain methacrylate monomers with a three phenyl ring core connected by an ester with a terminal alkoxy chain and hexamethylene spacer are synthesized by a multistep synthetic route. The corresponding polymers are realized by free radical solution polymerization. Two structurally similar mesogens are also synthesized for use as models to study the influence of the methacrylic unit on the mesophase characteristics. The molecular structure of the intermediates, monomers as well as the polymers is unambiguously confirmed by Fourier-transform infrared (FT-IR), solution 1H and 13C nuclear magnetic resonance (NMR) spectroscopy and by elemental analysis. The mesophase characteristics of all of the monomers and polymers are determined by hot-stage optical polarized microscopy (HOPM) and differential scanning calorimetry (DSC). These investigations revealed the existence of enantiotropic nematic (N), smectic A (SA) and smectic C (SC) mesophases. Furthermore, for a representative monomer and polymer, the presence of the smectic phase is confirmed by variable temperature X-ray diffraction (XRD) where a characteristic layer ordering is noticed. The molecular weight of the polymers is determined by gel permeation chromatography (GPC) and the values are found to be typically in the range of 2.0 × 103 to 3.7 × 103. The mesogenic polymers are also found to be stable up to 320 °C by thermogravimetric analysis (TGA). the Partner Organisations 2014.
- Siva Mohan Reddy,Narasimhaswamy,Mohana Raju
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supporting information
p. 4357 - 4364
(2014/12/09)
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- Synthetic studies of fisetin, myricetin and nobiletin analogs and related probe molecules
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We synthesized a series of analogs of fisetin, myricetin and nobiletin, as well as related fluorescein- and biotin-based flavone-probe molecules, on a suitable scale for biological and structure-activity relationship studies.
- Hiza, Aiki,Tsukaguchi, Yuta,Ogawa, Takahiro,Inai, Makoto,Asakawa, Tomohiro,Hamashima, Yoshitaka,Kan, Toshiyuki
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p. 1371 - 1396
(2016/10/12)
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- Neonicotinic analogues: Selective antagonists for α4β2 nicotinic acetylcholine receptors
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Nicotine is an agonist of nicotinic acetylcholine receptors (nAChRs) that has been extensively used as a template for the synthesis of α4β2-preferring nAChRs. Here, we used the N-methyl-pyrrolidine moiety of nicotine to design and synthesise novel α4β2-preferring neonicotinic ligands. We increased the distance between the basic nitrogen and aromatic group of nicotine by introducing an ester functionality that also mimics acetylcholine (Fig. 2). Additionally, we introduced a benzyloxy group linked to the benzoyl moiety. Although the neonicotinic compounds fully inhibited binding of both [α-125I]bungarotoxin to human α7 nAChRs and [3H]cytisine to human α4β2 nAChRs, they were markedly more potent at displacing radioligand binding to human α4β2 nAChRs than to α7 nAChRs. Functional assays showed that the neonicotinic compounds behave as antagonists at α4β2 and α4β2α5 nAChRs. Substitutions on the aromatic ring of the compounds produced compounds that displayed marked selectivity for α4β2 or α4β2α5 nAChRs. Docking of the compounds on homology models of the agonist binding site at the α4/β2 subunit interfaces of α4β2 nAChRs suggested the compounds inhibit function of this nAChR type by binding the agonist binding site.
- Faundez-Parraguez, Manuel,Farias-Rabelo, Nicolas,Gonzalez-Gutierrez, Juan Pablo,Etcheverry-Berrios, Alvaro,Alzate-Morales, Jans,Adasme-Carre?o, Francisco,Varas, Rodrigo,Bermudez, Isabel,Iturriaga-Vasquez, Patricio
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p. 2687 - 2694
(2013/06/27)
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- MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
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Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein
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Paragraph 00210
(2013/06/05)
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- Design, optimization, and biological evaluation of novel keto-benzimidazoles as potent and selective inhibitors of phosphodiesterase 10A (PDE10A)
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Our development of PDE10A inhibitors began with an HTS screening hit (1) that exhibited both high p-glycoprotein (P-gp) efflux ratios in rat and human and poor metabolic stability. On the basis of cocrystal structure of 1 in human PDE10A enzyme, we designed a novel keto-benzimidazole 26 with comparable PDE10A potency devoid of efflux liabilities. On target in vivo coverage of PDE10A in rat brain was assessed using our previously reported LC-MS/MS receptor occupancy (RO) technology. Compound 26 achieved 55% RO of PDE10A at 30 mg/kg po and covered PDE10A receptors in rat brain in a dose-dependent manner. Cocrystal structure of 26 in PDE10A confirmed the binding mode of the novel scaffold. Further optimization resulted in the identification of keto-benzimidazole 34, which showed an increased in vivo efficacy of 57% RO in rats at 10 mg/kg po and an improved in vivo rat clearance and oral bioavailability.
- Hu, Essa,Kunz, Roxanne K.,Chen, Ning,Rumfelt, Shannon,Siegmund, Aaron,Andrews, Kristin,Chmait, Samer,Zhao, Sharon,Davis, Carl,Chen, Hang,Lester-Zeiner, Dianna,Ma, Ji,Biorn, Christopher,Shi, Jianxia,Porter, Amy,Treanor, James,Allen, Jennifer R.
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p. 8781 - 8792
(2013/12/04)
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- NiCl2·6H2O/NaBH4 in methanol: A mild and efficient strategy for chemoselective deallylation/debenzylation of aryl ethers
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Deprotection of allyl/benzyl aryl ethers was achieved chemoselectively. The mild and inexpensive reagent combination of NiCl2·6H 2O/NaBH4 in methanol afforded the products in high yields, within a reaction time of 5-10 min.
- Chouhan, Mangilal,Kumar, Kapil,Sharma, Ratnesh,Grover, Vikas,Nair, Vipin A.
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supporting information
p. 4540 - 4543
(2013/08/23)
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- Substituted Fused Pyrimidine Compounds
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The present invention discloses substituted fused pyrimidine compounds of formula (I), their tautomers, polymorphs, stereoisomers, solvates, pharmaceutically acceptable salts, or pharmaceutical compositions containing them and methods of treating conditions and diseases that are mediated by adenosine receptor (AR) activity. The compounds of the present invention are useful in the treatment, prevention or suppression of diseases and disorders that may be susceptible to improvement by antagonism of the adenosine receptor, such as asthma, chronic obstructive pulmonary disorder, angiogenesis, pulmonary fibrosis, emphysema, allergic diseases, inflammation, reperfusion injury, myocardial ischemia, atherosclerosis, hypertension, congestive heart failure, retinopathy, diabetes mellitus, obesity, inflammatory gastrointestinal tract disorders, and/or autoimmune diseases.
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Page/Page column 29
(2012/05/20)
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- Liquid ammonia as a dipolar aprotic solvent for aliphatic nucleophilic substitution reactions
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The rate constants for the reactions of a variety of nucleophiles reacting with substituted benzyl chlorides in liquid ammonia (LNH3) have been determined. To fully interpret the associated linear free-energy relationships, the ionization constants of phenols ions in liquid ammonia were obtained using UV spectra. These equilibrium constants are the product of those for ion-pair formation and dissociation to the free ions, which can be separated by evaluating the effect of added ammonium ions. There is a linear relationship between the pKa of phenols in liquid ammonia and those in water of slope 1.68. Aminium ions exist in their unprotonated free base form in liquid ammonia and their ionization constants could not be determined by NMR. The rates of solvolysis of substituted benzyl chlorides in liquid ammonia at 25 °C show a Hammett ρ of zero, having little or no dependence upon ring substituents, which is in stark contrast with the hydrolysis rates of substituted benzyl halides in water, which vary 107 fold. The rate of substitution of benzyl chloride by substituted phenoxide ions is first order in the concentration of the nucleophile indicative of a SN2 process, and the dependence of the rate constants on the pKa of the phenol in liquid ammonia generates a Bronsted βnuc = 0.40. Contrary to the solvolysis reaction, the reaction of phenoxide ion with 4-substituted benzyl chlorides gives a Hammett ρ = 1.1, excluding the 4-methoxy derivative, which shows the normal positive deviation. The second order rate constants for the substitution of benzyl chlorides by neutral and anionic amines show a single Bronsted βnuc = 0.21 (based on the aqueous pKa of amine), but their dependence on the substituent in substituted benzyl chlorides varies with a Hammett ρ of 0 for neutral amines, similar to that seen for solvolysis, whereas that for amine anions is 0.93, similar to that seen for phenoxide ion.(Figure Presented)
- Ji, Pengju,Atherton, John,Page, Michael I.
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supporting information; scheme or table
p. 1425 - 1435
(2011/04/23)
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- SUBSTITUTED FUSED PYRIMIDINE COMPOUNDS
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The present invention discloses substituted fused pyrimidine compounds of formula I, their tautomers, polymorphs, stereoisomers, prodrugs, solvates, pharmaceutically acceptable salts, or pharmaceutical compositions containing them and methods of treating conditions and diseases that are mediated by adenosine receptor (AR) activity. The present invention also provides provide the use of compounds of formula (II), or its tautomers, polymorphs, stereoisomers, prodrugs, solvate or a pharmaceutically acceptable salts thereof, for the treatment of a pathological disease susceptible to improvement by antagonism of adenosine receptors. The compounds of the present invention are useful in the treatment, prevention or suppression of diseases and disorders that may be susceptible to improvement by antagonism of the adenosine receptor, such as asthma, chronic obstructive pulmonary disorder, angiogenesis, pulmonary fibrosis, emphysema, allergic diseases, inflammation, reperfusion injury, myocardial ischemia, atherosclerosis, hypertension, congestive heart failure, retinopathy, diabetes mellitus, obesity, inflammatory gastrointestinal tract disorders, and/or autoimmune diseases.
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Page/Page column 70
(2010/10/03)
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- Novel supramolecular side-chain banana-shaped liquid crystalline polymers containing covalent- and hydrogen-bonded bent cores
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Novel supramolecular side-chain banana-shaped liquid crystalline (LC) polymer complexes AmBn-N bearing various (m/n) molar ratios of hydrogen- and covalent-bonded bent-core components were acquired by the free radical polymerization, where the hydrogen-bonded (H-bonded) structures were executed via mixing equimolar portions of proton donor (H-donor) polymers AmBn (homopolymers/ copolymers) and pyridyl proton acceptor (H-acceptor) bent cores (small molecules). The influences of the molar ratios of bent-core H-bonded components in side-chain banana-shaped LC polymers and their corresponding polymer complexes on mesomorphic and electro-optical properties were first investigated, The voltage-dependent antiferroelectric properties of spontaneous polarization (Ps) values in the polar smectic phase of the supramolecular side-chain banana-shaped copolymers were also reported. The nematic and tilted smectic phases were verified by XRD measurements, and the SmCP phase was further confirmed by the triangular wave method. Surprisingly, a novel enantiotropic polar smectic (SmCPA) phase was generated in some bent-core side-chain polymer complexes AmBn-N. Therefore, a special approach to constructing (or stabilizing) the SmCP phase was first developed in this study by copolymerization of bent-core covalent- and H-bonded units in side-chain polymer complexes (with proper m/n molar ratios of 16/1 and 10/1) from both bent-core covalent- and H-bonded monomers (i.e., B and A-N units, respectively) without the SmCP phase.
- Wang, Ling-Yung,Tsai, Hsin-Yi,Lin, Hong-Cheu
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experimental part
p. 1277 - 1288
(2011/10/01)
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- 1,2,3,6-TETRAHYDROAZEPINO[4,5-B]INDOLE-5-CARBOXYLATE NUCLEAR RECEPTOR INHIBITORS
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Provided are certain 1,2,3,6- tetrahydroazepino[4,5-b]indole-5-carboxylate compounds which are useful for modulating the activity of nuclear receptors, such as farnesoid X receptors, and/or for the treatment, prevention, or amelioration diseases or disorders related to the activity of these receptors.
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Page/Page column 53
(2010/04/27)
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- PYRAZINE COMPOUNDS AS PHOSPHODIESTERASE 10 INHIBITORS
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Pyrazine compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.
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Page/Page column 94
(2010/06/15)
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- Synthesis and antimicrobial potential of Mannich bases of 4-chloro-3-{4-(chlorobenzyloxy)-benzoylhydrazono}-indolin-2-ones
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4-Chloro-3-{4-(chlorobenzyloxy)-benzoylhydrazono}-indolin-2-ones (1-4) were synthesised by the condensation of 4-(chlorobenzyloxy)-benzoylhydrazines and 4-chloroisatin. On being subjected to aminomethylation in the presence of formaldehyde and heterocyclic secondary amines, indolinones 1-4, furnished aminomethylated indolinones (Mannich bases) 5-20. The structures of the compounds have been established by means of elemental analysis and spectral data (IR, PMR and Mass). The compounds have been screened for their antimicrobial potential against human pathogenic bacteria and fungi.
- Rastogi, Nisheeth,Harrison, Darwin Anil,Tripathi, Diwakar,Shukla, Sarveshwar
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scheme or table
p. 991 - 995
(2010/08/05)
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- HETEROCYCLIC COMPOUNDS AS ADENOSINE RECEPTOR ANTAGONIST
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Compounds of the present disclosure are fused pyrimidine compounds of formula (I), its tautomers, polymorphs, stereoisomers, prodrugs, solvate or a pharmaceutically acceptable salts thereof, as Adenosine receptor antagonists. Processes of their preparation are also described in the disclosure.
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Page/Page column 69
(2009/10/22)
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- Counterattack mode differential acetylative deprotection of phenylmethyl ethers: Applications to solid phase organic reactions
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A counterattack protocol for differential acetylative cleavage of phenylmethyl ether has been developed. The phenylmethyl moiety is liberated as benzyl bromide that is isolated and reused providing advantages in terms of waste minimization/utilization and atom economy. The applicability of this methodology has been extended for solid phase organic reactions with the feasibility of reuse of the solid support.
- Chakraborti, Asit K.,Chankeshwara, Sunay V.
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supporting information; experimental part
p. 1367 - 1370
(2009/07/04)
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- CYCLIC TRIAZO AND DIAZO SODIUM CHANNEL BLOCKERS
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Compounds of general structure in which X and Y are each N or C with at least one of X and Y being N; Z is a single bond or an optionally substituted linking group R1 is hydrogen or a substituent group; R2 is amino or a substituent group; N* is amino when RI is hydrogen or =NH when R1 is a substituent group; or N* is a group NRaRb where Ra and Rb are independently H or an alkyl group; or N* is an optionally substituted piperazinyl ring; and A is an optionally substituted heterocyclic or carbocyclic ring system which may be linked to the triazo/diazo ring through R2 to form a fused multicyclic ring; are indicated as suitable for treatment of disorders in mammals that are susceptible to sodium channel blockers and antifolates, and particularly disorders such epilepsy, multiple sclerosis, glaucoma and uevitis, cerebral traumas and cerebral ischaemias, stroke, head injury, spinal cord injury, surgical trauma, neurodegenerative disorders, motorneurone disease, Alzheimer's disease, Parkinson's disease, chronic inflammatory pain, neuropathic pain, migraine, bipolar disorder, mood, anxiety and cognitive disorders, schizophrenia and trigeminal autonomic cephalalgias; for treatment of mammalian cancers; and for treatment of malaria.
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Page/Page column 33
(2009/08/16)
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- Benzyl protection of phenols under neutral conditions: Palladium-catalyzed benzylations of phenols
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Benzyl protection of phenols under neutral conditions was achieved by using a Pd(n3-C3H5)Cp-DPEphos catalyst. The palladium catalyst efficiently converted aryl benzyl carbonates into benzyl-protected phenols through the decarboxylative etherification. Alternatively, the nucleophilic substitution of benzyl methyl carbonates with phenols proceeded In the presence of the catalyst, yielding aryl benzyl ethers.
- Kuwano, Ryoichi,Kusano, Hiroki
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supporting information; experimental part
p. 1979 - 1982
(2009/04/10)
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- AZEPINOINDOLE DERIVATIVES AS PHARMACEUTICAL AGENTS
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The present invention relates to compounds of formula I, which exhibit affinity for the farnesoid X receptor.
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Page/Page column 157-158
(2008/06/13)
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- PESTICIDAL SUBSTITUTED PHENYLETHERS
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The invention relates to the use of phenylether derivatives of formula (I), to compositions thereof for the control of pests, including arthropods and helminths.
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Page/Page column 42; 44
(2008/06/13)
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- Synthesis and in vitro leishmanicidal activity of some hydrazides and their analogues
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Twenty-one hydrazides were synthesized by treating different esters with hydrazine hydrate. Substituted hydrazides were obtained by treating hydrazides with alkyl/aryl/acyl halides. Some of these compounds exhibit potential in vitro leishmanicidal activity. The structures of all the synthesized compounds were confirmed by spectroscopic analysis.
- Khan, Khalid Mohammad,Rasheed, Maimona,Ullah, Zia,Hayat, Safdar,Kaukab, Farhana,Choudhary, M. Iqbal,Ur-Rahman, Atta,Perveen, Shahnaz
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p. 1381 - 1387
(2007/10/03)
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