- Design, synthesis and biological evaluation of non-secosteriodal vitamin D receptor ligand bearing double side chain for the treatment of chronic pancreatitis
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Chronic pancreatitis (CP) is a serious disease that characterized by the progressive replacement of functional pancreas tissue by fibrotic tissue. Vitamin D receptor (VDR) plays a critical role in the development of CP, since it inhibits excessive deposit
- Kang, Zi-Sheng,Wang, Cong,Han, Xiao-Lin,Du, Jun-Jie,Li, Yan-Yi,Zhang, Can
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Read Online
- Catalytic Activation of Unstrained C(Aryl)-C(Alkyl) Bonds in 2,2′-Methylenediphenols
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Catalytic activation of unstrained and nonpolar C-C bonds remains a largely unmet challenge. Here, we describe our detailed efforts in developing a rhodium-catalyzed hydrogenolysis of unstrained C(aryl)-C(alkyl) bonds in 2,2′-methylenediphenols aided by removable directing groups. Good yields of the monophenol products are obtained with tolerating a wide range of functional groups. In addition, the reaction is scalable, and the catalyst loading can be reduced to as low as 0.5 mol %. Moreover, this method proves to be effective to cleave C(aryl)-C(alkyl) linkages in both models of phenolic resins and commercial novolacs resins. Finally, detailed experimental and computational mechanistic studies show that with C-H activation being a competitive but reversible off-cycle reaction, this transformation goes through a directed C(aryl)-C(alkyl) oxidative addition pathway.
- Dong, Guangbin,Ratchford, Benjamin L.,Xue, Yibin,Zhang, Rui,Zhu, Jun
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p. 3242 - 3249
(2022/02/23)
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- Semi-heterogeneous Dual Nickel/Photocatalysis using Carbon Nitrides: Esterification of Carboxylic Acids with Aryl Halides
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Cross-coupling reactions mediated by dual nickel/photocatalysis are synthetically attractive but rely mainly on expensive, non-recyclable noble-metal complexes as photocatalysts. Heterogeneous semiconductors, which are commonly used for artificial photosynthesis and wastewater treatment, are a sustainable alternative. Graphitic carbon nitrides, a class of metal-free polymers that can be easily prepared from bulk chemicals, are heterogeneous semiconductors with high potential for photocatalytic organic transformations. Here, we demonstrate that graphitic carbon nitrides in combination with nickel catalysis can induce selective C?O cross-couplings of carboxylic acids with aryl halides, yielding the respective aryl esters in excellent yield and selectivity. The heterogeneous organic photocatalyst exhibits a broad substrate scope, is able to harvest green light, and can be recycled multiple times. In situ FTIR was used to track the reaction progress to study this transformation at different irradiation wavelengths and reaction scales.
- Pieber, Bartholom?us,Malik, Jamal A.,Cavedon, Cristian,Gisbertz, Sebastian,Savateev, Aleksandr,Cruz, Daniel,Heil, Tobias,Zhang, Guigang,Seeberger, Peter H.
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supporting information
p. 9575 - 9580
(2019/06/25)
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- Discovery of novel nonsteroidal VDR agonists with novel diarylmethane skeleton for the treatment of breast cancer
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Vitamin D receptor (VDR) is recognized as a potential target for the treatment of breast cancer which is the most common malignancy among women in the world. In this study, a series of nonsecosteroidal VDR agonists with a novel diarylmethane skeleton was
- Wang, Cong,Wang, Bin,Hou, Siyuan,Xue, Lingjing,Kang, Zisheng,Du, Junjie,Li, Yanyi,Liu, Xuwentai,Wang, Qianqian,Zhang, Can
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p. 787 - 803
(2019/01/04)
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- Palladium-Catalyzed Aerobic Oxidative Carbonylation of C–H Bonds in Phenols for the Synthesis of p-Hydroxybenzoates
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This work reports the synthesis of p-hydroxybenzoates directly from phenols by oxidative carbonylation of phenolic C–H bonds, proceding through oxidative iodination. The developed methodology is efficient and economically attractive because phenols are cheap and easily available starting materials. This one-pot strategy was expediently applied to the synthesis of a variety of p-hydroxybenzoates by utilizing simple primary and secondary alcohols with different phenols under mild reaction conditions. Advantageously, the procedure has no need for co-catalysts, co-solvents or external ligands. The utilization of molecular oxygen as a terminal oxidant for C–H bond oxidation represents an additional benefit.
- Gaikwad, Vinayak V.,Bhanage, Bhalchandra M.
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p. 2877 - 2881
(2018/06/21)
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- Further Developments of the Phenyl-Pyrrolyl Pentane Series of Nonsteroidal Vitamin D Receptor Modulators as Anticancer Agents
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The vitamin D3 receptor (VDR), which belongs to the nuclear-receptor superfamily, is a potential molecular target for anticancer-drug discovery. In this study, a series of nonsteroidal vitamin D mimics with phenyl-pyrrolyl pentane skeletons wit
- Hao, Meixi,Hou, Siyuan,Xue, Lingjing,Yuan, Haoliang,Zhu, Lulu,Wang, Cong,Wang, Bin,Tang, Chunming,Zhang, Can
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supporting information
p. 3059 - 3075
(2018/04/23)
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- Double-benzene-ring compound as well as preparation method and medicinal purpose thereof
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The invention relates to a double-benzene-ring compound as well as a preparation method and a medical purpose thereof, and belongs to the field of medicinal chemistry. The invention also relates to the preparation method of the compound, a medicinal compo
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Paragraph 0109-0112
(2018/07/06)
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- N-substituted imidazole carboxylic ester compound, as well as preparation and medicinal application thereof
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The invention relates to a compound or stereisomer as shown in a general formula (I), solvate, pharmaceutically acceptable salt or eutectic crystal, as well as composition, preparation method and medicinal application thereof. The general formula (I) is as shown in the specification, and the definition of each substituent group is the same as that in the specification.
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Paragraph 0095; 0096; 0097; 0098; 0099; 0100
(2018/01/13)
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- HETEROCYCLIC AMIDES USEFUL AS PROTEIN MODULATORS
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Disclosed are compounds having the formula (I) wherein Ra, R1, R2, R3, R4, R5, R6, R7, and R8, are as defined herein, or a salt, particularly a pharmaceutic
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Page/Page column 96; 97
(2017/11/04)
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- HETEROCYCLIC GROUP CONTAINED AMINO-METHANOL DERIVATIVE, AND SALT, SYNTHETIC METHOD AND USE THEREOF
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The present invention provides a heterocyclic group contained amino-methanol derivative, and salt, a preparation method and use thereof, and belongs to the medical field. The heterocyclic group contained amino-methanol derivative and the salt thereof of the present invention are used for preparing medicines for immune suppression and for the treatment of organ transplant rejection, or medicines for treating immune mediated inflammatory diseases, such as multiple sclerosis, systemic lupus erythematosus and rheumatoid arthritis.
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Paragraph 0229; 0230
(2015/04/15)
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- HETEROCYCLIC GROUP CONTAINED AMINO-METHANOL DERIVATIVE, AND SALT, SYNTHETIC METHOD AND USE THEREOF
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The present invention provides a heterocyclic group contained amino-methanol derivative, and salt, a preparation method and use thereof, and belongs to the medical field. The heterocyclic group contained amino-methanol derivative and the salt thereof of the present invention are used for preparing medicines for immune suppression and for the treatment of organ transplant rejection , or medicines for treating immune mediated inflammatory diseases, such as multiple sclerosis, systemic lupus erythematosus and rheumatoid arthritis.
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Paragraph 0129; 0130; 0131
(2015/04/22)
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- Phenyl Esters Are Potent Inhibitors of Caseinolytic Protease P and Reveal a Stereogenic Switch for Deoligomerization
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Caseinolytic protease P (ClpP) represents a central bacterial degradation machinery that is involved in cell homeostasis and pathogenicity. The functional role of ClpP has been studied by genetic knockouts and through the use of beta-lactones, which remain the only specific inhibitors of ClpP discovered to date. Beta-lactones have served as chemical tools to manipulate ClpP in several organisms; however, their potency, selectivity and stability is limited. Despite detailed structural insights into the composition and conformational flexibility of the ClpP active site, no rational efforts to design specific non-beta-lactone inhibitors have been reported to date. In this work, an unbiased screen of more than 137000 compounds was used to identify five phenyl ester compounds as highly potent ClpP inhibitors that were selective for bacterial, but not human ClpP. The potency of phenyl esters largely exceeded that of beta-lactones in ClpP peptidase and protease inhibition assays and displayed unique target selectivity in living S. aureus cells. Analytical studies revealed that while phenyl esters are cleaved like native peptide substrates, they remain covalently trapped as acyl-enzyme intermediates in the active site. The synthesis of 36 derivatives and subsequent structure-activity relationship (SAR) studies provided insights into conserved structural elements that are important for inhibition potency and acylation reactivity. Moreover, the stereochemistry of a methyl-substituent at the alpha position to the ester, resembling amino acid side chains in peptide substrates, impacted ClpP complex stability, causing either dissociation into heptamers or retention of the tetradecameric state. Mechanistic insights into this intriguing stereo switch and the phenyl ester binding mode were obtained by molecular docking experiments.
- Hackl, Mathias W.,Lakemeyer, Markus,Dahmen, Maria,Glaser, Manuel,Pahl, Axel,Lorenz-Baath, Katrin,Menzel, Thomas,Sievers, Sonja,B?ttcher, Thomas,Antes, Iris,Waldmann, Herbert,Sieber, Stephan A.
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supporting information
p. 8475 - 8483
(2015/07/15)
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- Enantioselective synthesis of dictyoceratin-A (smenospondiol) and -C, hypoxia-selective growth inhibitors from marine sponge
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Total syntheses of (+)-dictyoceratin-C (1) and (+)-dictyoceratin-A (smenospondiol) (2), hypoxia-selective growth inhibitors isolated from marine sponge, were executed. The absolute stereochemistry of the each compound was determined through the enantiosel
- Sumii, Yuji,Kotoku, Naoyuki,Fukuda, Akinori,Kawachi, Takashi,Sumii, Yuta,Arai, Masayoshi,Kobayashi, Motomasa
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p. 966 - 975
(2015/03/04)
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- Novel nonsecosteroidal VDR agonists with phenyl-pyrrolyl pentane skeleton
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In order to find the vitamin D receptor (VDR) ligand whose VDR agonistic activity is separated from the calcemic activity sufficiently, novel nonsecosteroidal analogs with phenyl-pyrrolyl pentane skeleton were synthesized and evaluated for the VDR binding
- Shen, Wei,Xue, Jingwei,Zhao, Zekai,Zhang, Can
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p. 768 - 778
(2013/10/22)
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- MORPHOLINE-SPIROCYCLIC PIPERIDINE AMIDES AS MODULATORS OF ION CHANNELS
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The invention relates to morpholine spirocyclic piperidine amide compounds useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.
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Page/Page column 146
(2012/10/07)
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- STABLE ACRIDINIUM ESTERS WITH FAST LIGHT EMISSION
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Chemiluminescent acridinium esters are provided which are fast light emitting and hydrolytically stable. The chemiluminescent acridinium esters are useful labels in assays for detecting or quantifying analytes.
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Page/Page column 32
(2012/08/14)
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- The synthesis and biological evaluation of para-substituted phenolic N-alkyl carbamates as endocannabinoid hydrolyzing enzyme inhibitors
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A series of para-substituted phenolic N-alkyl carbamates were evaluated for their FAAH and MGL inhibitory activities. The compounds were generally selective for FAAH, with IC50 values in the nM range, whereas inhibition of MGL required concentrations three orders of magnitude higher. The most potent compounds, dodecylcarbamic acid 4-(4,5-dihydrothiazol-2-yl)phenyl (12) and 4-(1,2,3-thiadiazol-4-yl)phenyl (26) esters, inhibited FAAH and MGL with IC50 values at the low-nanomolar (IC50s; 0.0063 and 0.012 μM) and the low-micromolar ranges (IC50s; 2.1 and 1.0 μM), respectively. Compound 26 also inhibited both FAAH-dependent AEA uptake and AEA hydrolysis (IC50; 0.082 μM) by intact RBL2H3 cells, and could also reduce 2-AG hydrolysis by these cells at concentrations ≥0.030 μM.
- Minkkilae, Anna,Myllymaeki, Mikko J.,Saario, Susanna M.,Castillo-Melendez, Joel A.,Koskinen, Ari M.P.,Fowler, Christopher J.,Leppaenen, Jukka,Nevalainen, Tapio
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experimental part
p. 2994 - 3008
(2009/10/10)
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- Supramolecular-directed chiral induction in biaryl derivatives
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(Chemical Equation Presented) A thermodynamically controlled resolution has allowed for the generation of diastereomerically enriched complexes, by chirality transfer from an enantiopure building block to a dynamically racemic biaryl derivative. A switcha
- Etxebarria,Degenbeck,Felten,Serres,Nieto,Vidal-Ferran
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supporting information; experimental part
p. 8794 - 8797
(2010/03/04)
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- Triazole oxytocin antagonists: Identification of aryl ether replacements for a biaryl substituent
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Several potent aryl ether/triazole oxytocin antagonists are described. The lead compound in this series had significantly improved aqueous solubility over related systems containing a biaryl substituent.
- Brown, Alan,Brown, Lindsay,Brown, T. Bruce,Calabrese, Andrew,Ellis, Dave,Puhalo, Nicholas,Smith, Chris R.,Wallace, Olga,Watson, Lesa
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scheme or table
p. 5242 - 5244
(2009/05/07)
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- Novel bicyclic sulfonamide derivatives which are L-CPT1 inhibitors
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The invention is concerned with novel heterobicyclic derivatives of formula (I) wherein R1, R2, R3, R4, R5, R6, V, W, X and Y are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds inhibit L-CPT1 and can be used as medicaments.
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Page/Page column 36
(2010/11/28)
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- THERAPEUTIC COMPOUNDS
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This invention relates to a novel class of substituted amino-ethoxy benzene derivatives of formula (I) which are inhibitors of serine proteases and to their use in treating aberrant serine protease activity in a mammal, contraception, anti-coagulant methods and methods for treating aberrant cell proliferation, tumours, cancer, angiogenesis, angiogenesis-based retinopathies, autoimmummune disease, inflammation, skin disease, arthritis, rheutmatoid arthritis, asthma, osteoarthritis and multiple sclerosis. (I), Wherein Rm, Rn, Rp, Rq, V, W, X, Y and R8 are as defined in the claims.
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Page/Page column 57
(2010/11/27)
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- VASOPRESSIN V1A ANTAGONISTS
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The present invention concerns compounds inter alia according to general formula 1a. Compounds according to the invention are vasopressin V 1a receptor antagonists. Pharmaceutical compositions of the compounds are useful as treatment of dysmenorrhoea.
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Page/Page column 55
(2008/06/13)
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- Vesicant treatment with phenyl-thiophene type vitamin d receptor modulators
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The present invention relates to a method of treating or preventing damage to human skin cells by chemical vesicants by administering a non-secosteroidal, phenylthiophene compound with vitamin D receptor (VDR) modulating activity.
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Page/Page column 59
(2010/11/08)
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- SUBSTITUTED TRIAZOLE DERIVATIVES AS OXYTOCIN ANTAGONISTS
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The present invention relates to a class of substituted triazoles of formula (I) with activity as oxytocin antagonists, uses thereof, processes for the preparation thereof and compositions containing said inhibitors. These inhibitors have utility in a variety of therapeutic areas including sexual dysfunction, particularly premature ejaculation (P.E.).
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Page/Page column 64-65
(2010/02/13)
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- Design and synthesis of aromatic inhibitors of anthranilate synthase
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Aromatic analogues of chorismate were synthesised as potential inhibitors of anthranilate synthase. Molecular modelling using GOLD2.1 showed that these analogues docked into the active site of Serratia marcescens anthranilate synthase in the same conformation as chorismate. Most compounds were found to be micromolar inhibitors of S. marcescens anthranilate synthase. The most potent analogue, 3-(1-carboxy-ethoxy)-4-hydroxybenzoate (K1 3 μM). included a lactyl ether side chain. This appears to be a good replacement for the enol-pyruvyl side chain of chorismate. The Royal Society of Chemistry 2005.
- Payne, Richard J.,Toscano, Miguel D.,Bulloch, Esther M. M.,Aoell, Andrew D.,Abell, Chris
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p. 2271 - 2281
(2007/10/03)
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- NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
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Compounds represented by formula (1), wherein R1 is H, halogen, (C1-4)alkyl, O(C1-4)alkyl, and haloalkyl; R2 is H or methyl; R3 is H or (C1-4)alkyl; R4 is H or (C1-4)a
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- Non-nucleoside reverse transcriptase inhibitors
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Compounds represented by formula I: wherein R2 is selected from the group consisting of H, (C1-4)alkyl, halo, haloalkyl, OH, (C1-6)alkoxy, NH(C1-4alkyl) or N(C1-4alkyl)2; R4 is H
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Page/Page column 19
(2010/02/05)
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- VLA-4 INHIBITORS
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The present invention relates to a compound represented by the following formula (I): (wherein, W represents WA-A1 -WB - (in which, WA is substituted or unsubstituted aryl, etc., A1 is -NR1-, single bond, -C(O)-, etc., and WB is substituted or unsubstituted arylene, etc.), R is single bond, -NH-, -OCH2-, alkenylene, etc., X is -C(O) -CH2-, etc., and M is, for example, the following formula: (in which, R11, R12 and R13 each independently represents hydrogen, hydroxyl, amino, halogen, etc., R14 is hydrogen or lower alkyl, Y represents -CH2-O-, etc., Z is substituted or unsubstituted arylene, etc., A2 is single bond, etc, and R10 is hydroxyl or lower alkoxy)), or salt thereof; and a medicament containing the same. This compound or salt thereof selectively inhibits binding of cell adhesion molecules to VAL-4 and exhibits high bioavailability so that it is useful as a preventive and/or remedy for inflammatory diseases, autoimmune diseases, metastasis, bronchial asthma, rhinostenosis, diabetes, and the like.
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- PHENYL-THIOPHENE TYPE VITAMIN D RECEPTOR MODULATORS
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The present invention relates to novel, non-secosteroidal, phenyl-thiophene compounds with vitamin D receptor (VDR) modulating activity that are less hypercalcemic than 1α,25 dihydroxy vitamin D3. These compounds are useful for treating bone disease and p
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Page 170-171
(2008/06/13)
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