- Selective targeting of melanoma using N-(2-diethylaminoethyl) 4-[18F]fluoroethoxy benzamide (4-[18F]FEBZA): a novel PET imaging probe
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Background: The purpose of this study was to develop a positron emission tomography (PET) imaging probe that is easy to synthesize and selectively targets melanoma in vivo. Herein, we report the synthesis and preclinical evaluation of N-(2-diethylaminoeth
- Garg, Pradeep K.,Nazih, Rachid,Wu, Yanjun,Grinevich, Vladimir P.,Garg, Sudha
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Read Online
- A convenient synthesis of 2'- or 4'-hydroxycocaine
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A short, convenient and efficient synthesis of 2'- or 4'-hydroxycocaine is described. The key step involved selective hydrolysis/transesterification of the acetoxy group of 2'- or 4'-acetoxycocaine in methanol saturated with dry HCl gas.
- Singh, Satendra,Basmadjian, Garo P.,Avor, Kwasi,Pouw, Buddi,Seale, Thomas W.
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Read Online
- PROCESSES FOR PREPARING AN S1P-RECEPTOR MODULATOR
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This application relates to processes for preparing an S1P-receptor modulator "Compound 1", which is useful in the treatment of diseases or disorders associated with activity of S1P, including CNS disorders. The process comprises reacting "compound 2" with "compound 3" in the presence of a reducing agent.
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Page/Page column 33
(2021/05/07)
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- Structure-Activity Study of Nitazoxanide Derivatives as Novel STAT3 Pathway Inhibitors
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We identified nitazoxanide (NTZ) as a moderate STAT3 pathway inhibitor through immunoblot analysis and a cell-based IL-6/JAK/STAT3 pathway activation assay. A series of thiazolide derivatives were designed and synthesized to further validate the thiazolide scaffold as STAT3 inhibitors. Eight out of 25 derivatives displayed potencies greater than that of NTZ, and their STAT3 pathway inhibitory activities were found to be significantly correlated with their antiproliferative activities in HeLa cells. Derivatives 15 and 24 were observed to be more potent than the positive control WP1066, which is under phase I clinical trials. Compared with NTZ, 15 also exhibited much improved in vivo pharmacokinetic parameters in rats and efficacies against proliferations in multiple cancer cell lines, indicating a broad-spectrum effect of these thiazolides as antitumor agents targeted on STAT3.
- Lü, Zirui,Li, Xiaona,Li, Kebin,Wang, Cong,Du, Tingting,Huang, Wei,Ji, Ming,Li, Changhong,Xu, Fengrong,Xu, Ping,Niu, Yan
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p. 696 - 703
(2021/05/04)
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- Synthesis and antioxidant activities of berberine 9-: O -benzoic acid derivatives
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Although berberine (BBR) shows antioxidant activity, its activity is limited. We synthesized 9-O-benzoic acid berberine derivatives, and their antioxidant activities were screened via ABTS, DPPH, HOSC and FRAP assays. The para-position was modified with halogen elements on the benzoic acid ring, which led to an enhanced antioxidant activity and the substituent on the ortho-position was found to be better than the meta-position. Compounds 8p, 8c, 8d, 8i, 8j, 8l, and especially 8p showed significantly higher antioxidant activities, which could be attributed to the electronic donating groups. All the berberine derivatives possessed proper lipophilicities. In conclusion, compound 8p is a promising antioxidant candidate with remarkable elevated antioxidant activity and moderate lipophilicity.
- Liu, Yanfei,Long, Shuo,Zhang, Shanshan,Tan, Yifu,Wang, Ting,Wu, Yuwei,Jiang, Ting,Liu, Xiaoqin,Peng, Dongming,Liu, Zhenbao
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p. 17611 - 17621
(2021/05/29)
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- Using the liquid crystalline epoxy resin thermoset aromatic diamine
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PROBLEM TO BE SOLVED: To provide an aromatic diamine that gives a heat-cured product useful as an electric insulation material for radiating the heat generated from a semiconductor element and the like, and a liquid crystalline epoxy resin heat-cured product prepared therewith.SOLUTION: This invention relates to an aromatic diamine represented by formula (1), and a heat-cured product of the diamine and a liquid crystalline bisepoxide represented by formula (2) (where R-Rindependently represent a hydrogen atom, a C1-C6 alkyl group or a C1-C6 alkoxy group, m is an integer of 2-14, and Xis a divalent aromatic group).SELECTED DRAWING: None
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Paragraph 0054-0055
(2020/08/26)
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- Synthesis, biological evaluation and molecular modeling study of 2-amino-3,5-disubstituted-pyrazines as Aurora kinases inhibitors
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Serine/threonine protein kinases Aurora A, B, and C play essential roles in cell mitosis and cytokinesis, and a number of Aurora kinase inhibitors have been evaluated in the clinic. Herein we report the synthesis and their antiproliferation of 3,5-disubstituted-2-aminopyrazines as kinases inhibitors. Amongst, 4-((3-amino-6- (3,5-dimethylisoxazol-4-yl)pyrazin-2-yl)oxy)-N-(3-chlorophenyl) benzamide (12Aj) exhibited the strongest antiproliferative activities against U38, HeLa, HepG2 and LoVo cells with IC50 values were 11.5 ± 3.2, 1.34 ± 0.23, 7.30 ± 1.56 and 1.64 ± 0.48 μM, as well as inhibited Aurora A and B with the IC50 values were 90 and 152 nM, respectively. Molecular docking studies indicated that 12Aj appeared to form stable hydrogen bonds with either Aurora A or Aurora B. Furthermore, 12Aj arrested HeLa cell cycle in G2/M phase by regulating protein levels of cyclinB1 and cdc2. In addition, the bioinformatics prediction further revealed that 12Aj possessed good drug likeness using SwissADME. These results suggested that 12Aj was worthy of future development of potent anticancer agents as pan-Aurora kinases.
- Bo, Yong-Xin,Chen, Shi-Wu,Hao, Shu-Yi,Wang, Xing-Rong,Xiang, Rong,Xu, Yu
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- Meta -Substituted benzenesulfonamide: A potent scaffold for the development of metallo-β-lactamase ImiS inhibitors
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Metallo-β-lactamase (MβL) ImiS contributes to the emergence of carbapenem resistance. A potent scaffold, meta-substituted benzenesulfonamide, was constructed and assayed against MβLs. The twenty-one obtained molecules specifically inhibited ImiS (IC50 = 0.11-9.3 μM); 2g was found to be the best inhibitor (IC50 = 0.11 μM), and 1g and 2g exhibited partially mixed inhibition with Ki of 8.0 and 0.55 μM. The analysis of the structure-activity relationship revealed that the meta-substitutes improved the inhibitory activity of the inhibitors. Isothermal titration calorimetry (ITC) assays showed that 2g reversibly inhibited ImiS. The benzenesulfonamides exhibited synergistic antibacterial effects against E. coli BL21 (DE3) cells with ImiS, resulting in a 2-4-fold reduction in the MIC of imipenem and meropenem. Also, mouse experiments showed that 2g had synergistic efficacy with meropenem and significantly reduced the bacterial load in the spleen and liver after a single intraperitoneal dose. Tracing the ImiS in living E. coli cells by RS at a super-resolution level (3D-SIM) showed that the target was initially associated on the surface of the cells, then there was a high density of uniform localization distributed in the cytosol of cells, and it finally accumulated in the formation of inclusion bodies at the cell poles. Docking studies suggested that the sulfonamide group acted as a zinc-binding group to coordinate with Zn(ii) and the residual amino acid within the CphA active center, tightly anchoring the inhibitor at the active site. This study provides a highly promising scaffold for the development of inhibitors of ImiS, even the B2 subclasses of MβLs.
- Chen, Cheng,Gao, Han,Liu, Ya,Sun, Le-Yun,Yang, Ke-Wu,Zhen, Jian-Bin
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p. 259 - 267
(2020/04/17)
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- ESTROGEN RECEPTOR PROTEIN DEGRADERS
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The present disclosure provides compounds represented by Formula (I): A-L-B and the salts or solvates thereof, wherein A, L, and B are as defined in the specification. Compounds having Formula I are estrogen receptor degraders useful for the treatment of
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Paragraph 0181-0182
(2020/07/21)
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- Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER)
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The estrogen receptor (ER) is a validated target for the treatment of estrogen receptor-positive (ER+) breast cancer. Here, we describe the design, synthesis, and extensive structure-activity relationship (SAR) studies of small-molecule ERα degraders base
- Hu, Jiantao,Hu, Biao,Wang, Mingliang,Xu, Fuming,Miao, Bukeyan,Yang, Chao-Yie,Wang, Mi,Liu, Zhaomin,Hayes, Daniel F.,Chinnaswamy, Krishnapriya,Delproposto, James,Stuckey, Jeanne,Wang, Shaomeng
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p. 1420 - 1442
(2019/01/30)
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- 4-(2-OXIRANYLMETHOXY) BENZOIC ACID ALKENYL ESTER AND METHOD FOR PRODUCING THE SAME
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PROBLEM TO BE SOLVED: To provide a novel aromatic compound having an epoxy group and alkenyl group, useful as a compatibilizer of various resins, a coating, an adhesive, a fiber modifier, a dispersant, a resist material or the like, and provide a novel me
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Paragraph 0062
(2019/04/26)
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- Synthesis and cytotoxicity of novel simplified eleutherobin analogues as potential antitumour agents
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Mixed simplified structures containing the paclitaxel and eleutherobin pharmacophore moieties were analyzed using molecular docking techniques and synthesized based on adamantane and 8-oxabicyclo[3.2.1]octane scaffolds. The crucial role of substituents' stereochemistry in biological activity is discussed. At micromolar concentrations the selected analogues interfered with tubulin dynamics in vitro and in a living organism. Furthermore, new compounds were cytotoxic against human tumour cell lines. The simplified eleutherobin analogues may be considered as prototypes of a new class of antitumour agents.
- Sosonyuk, Sergey E.,Peshich, Anita,Tutushkina, Anastasia V.,Khlevin, Dmitry A.,Lozinskaya, Natalia A.,Gracheva, Yulia A.,Glazunova, Valeria A.,Osolodkin, Dmitry I.,Semenova, Marina N.,Semenov, Victor V.,Palyulin, Vladimir A.,Proskurnina, Marina V.,Shtil, Alexander A.,Zefirov, Nikolay S.
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supporting information
p. 2792 - 2797
(2019/03/12)
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- RADIOLABELED COMPOUNDS
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The present invention relates to radiolabeled compounds of formula (I) wherein either A, B, R1, R2, is labeled with a radionuclide selected from 3H, 11C and 18F and its use for imaging alpha synuclein and/or Abeta deposits in mammals.
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Page/Page column 23; 24
(2019/07/13)
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- COMPOSITIONS AND METHODS OF MAKING EXPANDED HEMATOPOIETIC STEM CELLS USING DERIVATIVES OF FLUORENE
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This invention is directed to, inter alia, compounds, methods, systems, and compositions for the maintenance, enhancement, and expansion of hematopoietic stem cells derived from one or more sources of CD34+ cells. Sources of CD34+ cells include bone marrow, cord blood, mobilized peripheral blood, and non-mobilized peripheral blood. Also provided herein are compounds of Formula I which are useful in maintaining, enhancing, and expanding of hematopoietic stem cells.
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Paragraph 0432
(2019/05/15)
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- Structure-activity relationship study and biological evaluation of SAC-Garlic acid conjugates as novel anti-inflammatory agents
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A series of S-allyl-L-cysteine (SAC) with garlic acid conjugates as anti-inflammatory agents were designed and synthesized. Among the 40 tested compounds, SMU-8c exhibited the most potent inhibitory activity to Pam3CSK4-induced nitric oxide (NO) in RAW264.7 macrophages with IC50 of 22.54 ± 2.60 μM. The structure-activity relationship (SAR) study suggested that the esterified carboxyl group, carbon chain extension and methoxylation phenol hydroxy could improve the anti-inflammatory efficacy. Preliminary anti-inflammatory mechanism studies showed that SMU-8c significantly down-regulated the levels of Pam3CSK4 triggered TNF-α cytokine in human THP-1 cells, mouse RAW 264.7 macrophages, as well as in ex-vivo human peripheral blood mononuclear cells (PBMC) with no influence on cell viability. SMU-8c specifically blocked the Pam3CSK4 ignited secreted embryonic alkaline phosphatase (SEAP) signaling with no influence to Poly I:C or LPS triggered TLR3 or TLR4 signaling. Moreover, SMU-8c suppressed TLR2 in HEK-Blue hTLR2 cells and inhibited the formation of TLR1-TLR2, and TLR2-TLR6 complex in human PBMC. In summary, SMU-8c inhibited the TLR2 signaling pathway to down-regulate the inflammation cytokines, such as NO, SEAP and TNF-α, to realize its anti-inflammatory activity.
- Bi, Jingjie,Wang, Wenqing,Du, Junxi,Chen, Kun,Cheng, Kui
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p. 233 - 245
(2019/07/02)
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- Construction of 3D Antioxidants with Nucleosides as the Core: Inhibition of DNA Oxidation
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We herein attach ferulic and caffeic acids to -OH and -NH2 in cytidine, uridine, adenosine, or guanosine for achieving antioxidative hybrids with three-dimensional (3D) configuration. In the case of molecular docking computation, the nucleoside
- Zhao, Peng-Fei,Liu, An,Wei, Ming-Guang,Liu, Zai-Qun
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p. 15854 - 15864
(2019/12/25)
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- Uracil Hydroxybenzamides as Potential Antidiabetic Prodrugs
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A series of N1, N3-bis-hydroxybenzoyl, -acetoxybenzoyl, and -methoxybenzoyl uracil derivatives were synthesized. All compounds were screened for the ability to rupture protein cross links and antiglycating, chelating, and antiaggregant properties, which are most significant for pharmacological treatment of thrombosis and angio-, nephro-, encephalo-, and cardiopathies. 1,3-bis-(4-Methoxybenzoyl)pyrimidine-2,4(1H,3H)-dione was a promising antidiabetic agent with all studied activities.
- Brel’,Spasov,Lisina,Popov,Kucheryavenko,Litvinov,Salaznikova,Rashchenko
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p. 511 - 515
(2019/11/22)
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- A BISPHENOL DERIVATIVE HAVING AN ESTER BOND
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PROBLEM TO BE SOLVED: To provide a production intermediate useful for obtaining a compound having an ester bond, and a production method to obtain a compound having an ester bond, using the same, with convenience and high purity; specifically, to provide a bisphenol derivative having an ester bond, a method for producing the same, and a compound produced from the bisphenol derivative as an intermediate; and to further provide a polymer obtained by the polymerization of a polymerizable composition containing the compound produced from the bisphenol derivative as an intermediate, and an optical anisotropic body using the polymer. SOLUTION: A bisphenol derivative having an ester bond is represented by general formula (I-C), where at least one of A1 and A2 is substituted with one substituent L. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPO&INPIT
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Paragraph 0221-0223
(2018/06/13)
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- Discovery of β-Adrenergic Receptors Blocker-Carbonic Anhydrase Inhibitor Hybrids for Multitargeted Antiglaucoma Therapy
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The combination of a β-adrenergic receptors (AR) blocker and a carbonic anhydrase (CA, EC 4.2.1.1) inhibitor in eye drops formulations is one of the most clinically used treatment for glaucoma. A novel approach consisting of single-molecule, multitargeted compounds for the treatment of glaucoma is proposed here by designing compounds which concomitantly interact with the β-adrenergic and CA targets. Most derivatives of the two series of benzenesulfonamides incorporating 2-hydroxypropylamine moieties reported here exhibited striking efficacy against the target hCA II and XII, whereas a subset of compounds also showed significant modulation of β1- and β2-ARs. X-ray crystallography studies provided rationale for the observed hCA inhibition. The best dual-agents decreased IOP more effectively than clinically used dorzolamide, timolol, and the combination of them in an animal model of glaucoma. The reported evidence supports the proof-of-concept of β-ARs blocker-CAI hybrids for antiglaucoma therapy with an innovative mechanism of action.
- Nocentini, Alessio,Ceruso, Mariangela,Bua, Silvia,Lomelino, Carrie L.,Andring, Jacob T.,McKenna, Robert,Lanzi, Cecilia,Sgambellone, Silvia,Pecori, Riccardo,Matucci, Rosanna,Filippi, Luca,Gratteri, Paola,Carta, Fabrizio,Masini, Emanuela,Selleri, Silvia,Supuran, Claudiu T.
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p. 5380 - 5394
(2018/06/11)
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- Synthesis and anticancer activity evaluation of some new derivatives of 2-(4-benzoyl-1-piperazinyl)-quinoline and 2-(4-cinnamoyl-1-piperazinyl)-quinoline
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In this study, we designed and synthesized twenty new derivatives of 2-(4-benzoyl-1-piperazinyl)- quinoline and 2-(4-cinnamoyl-1-piperazinyl)-quinoline with potential anticancer activity. The structures of synthesized compounds were confirmed by 1H and 13C NMR spectroscopy and MS spectrometry. The activity of novel compounds was evaluated in the cell viability assay as well as in the wound healing assay. Presented data show that examined substances have anticancer activity in cell culture. Seven compounds which showed a high rate of cell growth inhibition were selected for further studies. Three of them strongly reduced the growth of B16F10 cells. The novel compounds constitute a good base for further studies and optimization of structure for new therapeutically effective anti-cancerous drugs.
- Kubica, Krzysztof P.,Taciak, Przemys?aw P.,Czajkowska, Agnieszka,Stokfisz-Ignasiak, Alicja,Wyrebiak, Rafa?,Podsadni, Piotr,M?ynarczuk-Bia?y, Izabela,Malejczyk, Jacek,Mazurek, Aleksander P.
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p. 891 - 901
(2018/09/25)
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- Evaluation of N-Hydroxy-, N-Metoxy-, and N-Acetoxybenzoyl-Substituted Derivatives of Thymine and Uracil as New Substances for Prevention and Treatment of Long-Term Complications of Diabetes Mellitus
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New uracil and thymine derivatives, N1-,N3- and N1,N3-(RO-benzoyl)-(1H,3H)-pyrimidine- 2,4-diones, were synthesized (RO- is hydroxy, acetoxy- or methoxy-group). The compounds were studied in a complex of in vitro tests for the ability to inhibit the development of long-term complications of diabetes. Their ability to cleave cross-links of proteins has been evaluated. The most significant ways of pharmacological correction of thrombosis, angio-, nephro-, encephalo-, and cardiopathy, antiglycation, chelating, and antiplatelet activities, have been established. The most active compound in terms of antiplatelet action, N1- hydroxybenzoyluracil, exceeded acetylsalicylic acid by ~44%. In terms of their ability to chelate copper (II) cations, all compounds (with the exception of 1,3-bis(3-hydroxybenzoyl)-(1H,3H)-pyrimidine-2,4-dione that was not not studied in this test) showed the activity, whose IC50 fell in the range between that for pioglitazone (44.1 μM) and pyridoxamine (136.7 μM) comparison drugs. The best antiglycation effect at the 1 mM concentration was observed for N1,N3-bismethoxy- and N1,N3-bisacetoxybenzoyl derivatives of thymine. The maximum activity to cleave cross-links of proteins (C = 1 mM), comparable to that of alagebrium, was established for 1,3-bis(4-methoxybenzoyl)uracil, for which also high rates of other estimated activities were noted. Thus, the N1-,N3- and N1,N3-(RO-benzoyl) derivatives of uracil and thymine are promising basiсs for creating drugs that suppress the development of long-term complications of diabetes.
- Spasov,Brel,Litvinov,Lisina,Kucheryavenko,Budaeva, Yu. N.,Salaznikova,Rashchenko,Shamshina,Batrakov,Ivanov
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p. 769 - 777
(2019/02/26)
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- Thermotropic liquid crystalline polyesters derived from 2-chloro hydroquinone
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Abstract: Synthesis of thermotropic liquid crystalline polyesters derived from bis[4-hydroxy benzoyloxy]-2-chloro-1,4-benzene (BHBOCB) and aliphatic dicarboxylic acid chlorides by interfacial polycondensation methodology is presented. Synthesised polyesters consist of bis[4-hydroxy benzoyloxy]-2-chloro-1,4-benzene as a mesogen and aliphatic diacid chloride as flexible spacer. The length of oligomethylene units in the polymer was varied from the trimethylene to the dodecamethylene groups. Synthesized polyesters were characterized by differential scanning calorimetry and optical microscopy. The transition temperatures and thermodynamic properties were studied for all these polymers. These polyesters exhibited thermotropic liquid crystalline behavior and showed nematic texture except decamethylene spacer. Decamethylene spacer based polyester showed marble texture of smectic C. Mesophase stability of these polyesters was higher than 123 °C (except first heating cycle of PE-1). Graphical Abstract:: SYNOPSIS The present study deals with the synthesis of thermotropic liquid crystalline polyesters derived from bis[4-hydroxy benzoyloxy]-2-chloro-1,4-benzene (BHBOCB) and aliphatic dicarboxylic acid chlorides by interfacial polycondensation methodology. [Figure not available: see fulltext.].
- Manurkar, Nagesh,More, Sayaji,Mulani, Khudbudin,Ganjave, Nitin,Chavan, Nayaku
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p. 1461 - 1468
(2017/09/27)
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- C-F bond cleavage enabled redox-neutral [4+1] annulation via C-H bond activation
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Using α,α-difluoromethylene alkyne as a nontraditional one-carbon reaction partner, a synthetically novel method for the construction of isoindolin-1-one derivatives via Rh(III)-catalyzed [4+1] annulation reaction is reported. The 2-fold C-F bond cleavage not only enables the generation of desired product under an overall oxidant-free condition but also results in a net migration of carbon-carbon triple bond. In addition, the present reaction protocol exhibits a tolerance of a wide spectrum of functional groups due to the mild reaction conditions employed.
- Wang, Cheng-Qiang,Ye, Lu,Feng, Chao,Loh, Teck-Peng
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supporting information
p. 1762 - 1765
(2017/02/15)
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- Secondary sulfonamides as effective lactoperoxidase inhibitors
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Secondary sulfonamides (4a-8h) incorporating acetoxybenzamide, triacetoxybenzamide, hydroxybenzamide, and trihydroxybenzamide and possessing thiazole, pyrimidine, pyridine, isoxazole and thiadiazole groups were synthesized. Lactoperoxidase (LPO, E.C.1.11.1.7), as a natural antibacterial agent, is a peroxidase enzyme secreted from salivary, mammary, and other mucosal glands. In the present study, the in vitro inhibitory effects of some secondary sulfonamide derivatives (4a-8h) were examined against LPO. The obtained results reveal that secondary sulfonamide derivatives (4a-8h) are effective LPO inhibitors. The Ki values of secondary sulfonamide derivatives (4a-8h) were found in the range of 1.096 ± 10-3 to 1203.83 μM against LPO. However, the most effective inhibition was found for N-(sulfathiazole)-3,4,5-triacetoxy.
- K?ksal, Zeynep,Kalin, Ramazan,Camadan, Yasemin,Usanmaz, Hande,Almaz, Züleyha,Gül?in, Ilhami,Gokcen, Taner,G?ren, Ahmet Ceyhan,Ozdemir, Hasan
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- A Tandem Ring Opening/Closure Reaction in A BF3-Mediated Rearrangement of Spirooxindoles
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Treatment of the readily accessible spiro-cyclohexadienones from the PhI(OCOCF3)2-mediated spiro-cyclization of N-substituted benzanilides, with BF3?Et2O initiates a tandem ring opening/closure reaction leading to the formation of the biologically interesting 8-hydroxy-phenanthridin-6(5H)-one compounds. This unique rearrangement pattern involves the ‘migration’ of the electron-deficient N-methyl carbamoyl moiety rather than the electron-rich aryl group as observed and reported previously in all other similar transformations. (Figure presented.).
- Guo, Xuliang,Xing, Qingyu,Lei, Kunhua,Zhang-Negrerie, Daisy,Du, Yunfei,Zhao, Kang
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supporting information
p. 4393 - 4398
(2017/10/23)
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- The Conversion of tert-Butyl Esters to Acid Chlorides Using Thionyl Chloride
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The reaction of tert-butyl esters with SOCl2 at room temperature provides acid chlorides in unpurified yields of 89% or greater. Benzyl, methyl, ethyl, and isopropyl esters are essentially unreactive under these conditions, allowing for the selective conversion of tert-butyl esters to acid chlorides in the presence of other esters.
- Greenberg, Jacob A.,Sammakia, Tarek
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p. 3245 - 3251
(2017/03/23)
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- INHIBITORS OF BRUTON'S TYROSINE KINASE
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Disclosed herein are compounds that inhibit Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. In addition, reversible inhibitors of Btk are also described. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.
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-
Paragraph 00659
(2016/01/25)
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- Nickel(II)-Mediated Regioselective C H Monoiodination of Arenes and Heteroarenes by using Molecular Iodine
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The 8-aminoquinoline-directed, nickel(II)-mediated ortho-iodination of benzamides using molecular iodine has been developed. The process is highly regioselective and furnishes only monoiodinated products. A broad range of arenes and heteroarenes with diverse functional groups provided monoiodinated products in good to excellent yields. (Figure presented.) .
- Khan, Bhuttu,Kant, Ruchir,Koley, Dipankar
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supporting information
p. 2352 - 2358
(2016/07/28)
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- POLYORGANOSILOXANE COMPOUND, METHOD FOR PREPARING THE SAME, AND COPOLYCARBONATE RESIN COMPRISING THE SAME
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A polyorganosiloxane compound, a method of preparing the same, and a copolycarbonate resin comprising the same are disclosed. Particularly, a copolycarbonate resin, which may be applied to a variety of applications, and in particular, comprises a polyorganosiloxane compound used as an impact modifier, a modifier, or a comonomer of a copolycarbonate resin and has improved mechanical properties such as low-temperature impact strength, is disclosed.
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-
Paragraph 0085; 0086; 0092
(2016/06/13)
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- DIOL MONOMER, ITS POLYCARBONATE AND ARTICLE CONTAINING THE SAME
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The present invention relates to a diol-based compound, polycarbonate thereof, and an article comprising the same. According to the present invention, provided are: a novel monomer having greater effects in improving the degree of heat resistance while ha
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-
Paragraph 0091; 0093; 0094
(2016/10/07)
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- A class of sulfonamides as carbonic anhydrase I and II inhibitors
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Four groups of novel sulfonamide derivatives: (i) acetoxybenzamide, (ii) triacetoxybenzamide, (iii) hydroxybenzamide and (iv) trihydroxybenzamide, all having thiazole, pyrimidine, pyridine, isoxazole and thiadiazole moieties were prepared and their inhibitory effects were studied on two metalloenzymes, i.e. carbonic anhydrase isozymes (hCA I and II), purified from human erythrocyte cells by Sepharose-4B-l-tyrosine-sulfanilamide affinity chromatography. These enzymes are present in almost all living organisms to catalyse the synthesis of bicarbonate ion (HCO3 ?) from carbon dioxide and water. The sulfonamide derivatives were found to be active against hCA I and II in the range of 2.62–136.54 and 5.74–210.58 nM, respectively.
- Gokcen, Taner,Gulcin, Ilhami,Ozturk, Turan,Goren, Ahmet C.
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p. 180 - 188
(2016/12/14)
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- DIOL MONOMER, ITS POLYCARBONATE AND ARTICLE CONTAINING THE SAME
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The present invention relates to a diol-based compound, polycarbonate thereof, and an article comprising the same. According to the present invention, provided are: a novel monomer having great effects in improving heat resistance while having less effect
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-
Paragraph 0083; 0084
(2017/02/28)
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- DIOL MONOMER, ITS POLYCARBONATE AND ARTICLE CONTAINING THE SAME
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The present invention relates to a diol monomer, a polycarbonate of the same, and an article including the same. More specifically, the present invention relates to a chemical compound represented by chemical formula 1, a polycarbonate, and an article pol
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-
Paragraph 0072; 0073; 0074
(2017/03/23)
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- Discovery of Novel and Orally Bioavailable Inhibitors of PI3 Kinase Based on Indazole Substituted Morpholino-Triazines
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A new class of potent PI3Kα inhibitors is identified based on aryl substituted morpholino-triazine scaffold. The identified compounds showed not only a high level of enzymatic and cellular potency in nanomolar range but also high oral bioavailability. The three lead molecules (based on their in vitro potency) when evaluated further for in vitro metabolic stability as well as pharmacokinetic profile led to the identification of 26, as a candidate for further development. The IC50 and EC50 value of 26 is 60 and 500 nM, respectively, for PI3Kα enzyme inhibitory activity and ovarian cancer (A2780) cell line. The identified lead also showed a high level of microsomal stability and minimal inhibition activity for CYP3A4, CYP2C19, and CYP2D6 at 10 μM concentrations. The lead compound 26, demonstrated excellent oral bioavailability with an AUC of 5.2 μM at a dose of 3 mpk in mice and found to be well tolerated in mice when dosed at 30 mpk BID for 5 days.
- Dugar, Sundeep,Hollinger, Frank P.,Mahajan, Dinesh,Sen, Somdutta,Kuila, Bilash,Arora, Reena,Pawar, Yogesh,Shinde, Vaibhav,Rahinj, Mahesh,Kapoor, Kamal K.,Bhumkar, Rahul,Rai, Santosh,Kulkarni, Rakesh
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supporting information
p. 1190 - 1194
(2015/12/23)
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- Design, synthesis and cytotoxic evaluation of novel imatinib amide derivatives that target Abl kinase
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Novel imatinib amide derivatives (a1-28, b1-9) were synthesized and evaluated for their biological activities. All compounds were characterized by 1H NMR, MS and elemental analysis. Among all the derivatives, compounds a4, a10, a21, b1 and b2 displayed the most significant ability of inhibiting K562 cell proliferation with the IC50 values of 0.67, 0.66, 0.65, 0.59 and 0.62 μM, respectively, indicating that these compounds were potent inhibitors of Bcr-Abl in leukemic K562 cells, comparable to the reference compound imatinib. Molecular docking study was performed to position compounds a21 and b1 into the active site of Abl to determine the probable binding modes
- Yao, Ri-Sheng,Guan, Qiu-Xiang,Lu, Xiao-Qin,Ruan, Ban-Feng
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- Study on the synthesis of sulfonamide derivatives and their interaction with bovine serum albumin
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Three sulfonamide derivatives (SAD) were first synthesized from p-hydroxybenzoic acid and sulfonamides (sulfadimidine, sulfamethoxazole and sulfachloropyridazine sodium) and were characterized by elemental analysis, 1H NMR and MS. The interaction between bovine serum albumin (BSA) and SAD was studied using UV/vis absorption spectroscopy, fluorescence spectroscopy, time-resolved fluorescence spectroscopy and circular dichroism spectra under imitated physiological conditions. The experimental results indicated that SAD effectively quenched the intrinsic fluorescence of BSA via a static quenching process. The thermodynamic parameters showed that hydrogen bonding and van der Waal's forces were the predominant intermolecular forces between BSA and two SADs [4-((4-(N-(4,6-dimethylpyrimidin-2-yl)sulfamoyl)phenyl)carbamoyl)phenyl acetate and 4-((4-(N-(5-methylisoxazol-3-yl)sulfamoyl)phenyl)carbamoyl)phenyl acetate], but hydrophobic forces played a major role in the binding process of BSA and 4-((4-(N-(6-chloropyridazin-3-yl)sulfamoyl)phenyl) carbamoyl)phenyl acetate. In addition, the effect of SAD on the conformation of BSA was investigated using synchronous fluorescence spectroscopy and circular dichroism spectra. Molecular modeling results showed that SAD was situated in subdomain IIA of BSA.
- Zhang, Xuehong,Lin, Yijie,Liu, Lina,Lin, Cuiwu
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p. 269 - 279
(2015/04/14)
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- METHOD FOR MANUFACTURING P-HYDROXY BENZOIC ACID ALLYL POLYMER
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PROBLEM TO BE SOLVED: To provide a method for efficiently manufacturing p-hydroxy benzoic acid allyl polymer having high antibacterial property. SOLUTION: There is provided a method for manufacturing p-hydroxy benzoic acid allyl polymer including (A) a pr
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Paragraph 0045
(2017/02/24)
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- NOVEL TRIAZINE COMPOUNDS
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The present invention relates to novel triazine compounds of formula (1). The present invention also discloses compounds of formula I along with other pharmaceutical ac-ceptable excipients and use of the compounds to modulate the PI3K/ mTOR pathway
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Page/Page column 122; 123
(2014/02/16)
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- Synthesis and characterization of Triad based rigid mesogenic diols derived from Hydroquinone and 4-hydroxybenzoic acid
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Triad based rigid mesogenic diols have been synthesized by four step synthesis method using protection-deprotecti method. Hydroquinone and 4-hydroxy benzoic acid have been used as starting materials. Synthesized diols have be characterized by IR, 1H and 13C NMR, and mass spectroscopic methods. Thermal properties have been determined b thermo gravimetric analysis method and degree of crystallinity have been measured by wide angle X-ray techniqu Substituted hydroquinones (methyl and chloro) have been used to study the effect of substitution on physical and therm properties. Synthesis of rigid mesogenic diol monomer using p-hydroxy benzoic acid and hydroquinone is reported, which a facile route. Hydrolysis of diacetate derivatives of rigid mesogenic diols is performed in good yields, even though tw types of ester groups present in the same moiety, aromatic and aliphatic. The experimental results reveal that hydroquino based rigid triad mesogenic diol have high thermal stability and degree of crystallinity as compared to methyl- and chlor substituted rigid triad mesogenic diols.
- Mulani, Khudbudin B.,Ganjave, Nitin V.,Chavan, Nayaku N.
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p. 591 - 596
(2014/06/23)
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- 2-Diazo-1-(4-hydroxyphenyl)ethanone: A versatile photochemical and synthetic reagent
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α-Diazo arylketones are well-known substrates for Wolff rearrangement to phenylacetic acids through a ketene intermediate by either thermal or photochemical activation. Likewise, α-substituted p-hydroxyphenacyl (pHP) esters are substrates for photo-Favorskii rearrangements to phenylacetic acids by a different pathway that purportedly involves a cyclopropanone intermediate. In this paper, we show that the photolysis of a series of α-diazo-p- hydroxyacetophenones and p-hydroxyphenacyl (pHP) α-esters both generate the identical rearranged phenylacetates as major products. Since α-diazo-p-hydroxyacetophenone (1a, pHP N2) contains all the necessary functionalities for either Wolff or Favorskii rearrangement, we were prompted to probe this intriguing mechanistic dichotomy under conditions favorable to the photo-Favorskii rearrangement, i.e., photolysis in hydroxylic media. An investigation of the mechanism for conversion of 1a to p-hydroxyphenyl acetic acid (4a) using time-resolved infrared (TRIR) spectroscopy clearly demonstrates the formation of a ketene intermediate that is subsequently trapped by solvent or nucleophiles. The photoreaction of 1a is quenched by oxygen and sensitized by triplet sensitizers and the quantum yields for 1a-c range from 0.19 to a robust 0.25. The lifetime of the triplet, determined by Stern-Volmer quenching, is 31 ns with a rate for appearance of 4a of k = 7.1 × 10 6 s-1 in aq. acetonitrile (1:1 v:v). These studies establish that the primary rearrangement pathway for 1a involves ketene formation in accordance with the photo-Wolff rearrangement. Furthermore we have also demonstrated the synthetic utility of 1a as an esterification and etherification reagent with a variety of substituted α-diazo-p- hydroxyacetophenones, using them as synthons for efficiently coupling it to acids and phenols to produce pHP protect substrates. The Royal Society of Chemistry and Owner Societies.
- Senadheera, Sanjeewa N.,Evans, Anthony S.,Toscano, John P.,Givens, Richard S.
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p. 324 - 341
(2014/02/14)
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- Efficient preparation of novel phenolic surfactants for self-assembled monolayers
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Novel molecules have been synthesized that combine the phenolic nature of tannins and self-assembling properties of surfactants. These single-chain (C12) surfactants with potential biocompatibility have been synthesized with an ω-thiol or disulfide functionality, both commonly used anchors in self-assembly onto gold surfaces, using a modular route. Protecting groups for the phenol and thiol moieties played a key role for overcoming the challenges often associated with the purification of surfactants. The tasks of unmasking the thiol moiety and simultaneously deprotecting the acetyl protecting groups of the phenols were accomplished using sodium thiomethoxide. This modular route can be extended to synthesize other surfactants with the potential ability to form robust layers with biocompatible properties.
- Rajasingam, Arison,Schmidt, Rolf,Woo, Simon,DeWolf, Christine,Forgione, Pat
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p. 1066 - 1075
(2014/04/03)
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- Synthesis and bioactivity of resveratrol analogues
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It has been reported that resveratrol enhanced SIRT1 expression and significantly mimicked calorie restriction by stimulating Sir2 which is the most homologic homologue of SIRT1 of mammalian. A series of novel resveratrol derivatives were designed and synthesized as novel SIRT1 activator candidates. These synthesized compounds were characterized by spectral (1H NMR) analysis and examined for their Sir2 activation against yeast parental strain-BY4743 at a concentration of 100 μM/L by Bioscreen C MBR machine. Several compounds showed a promising Sir2 activation activity compared with resveratrol. Meanwhile, the structure-activity relationships with Sirt2 activation activities were also discussed.
- Ao, Junli,Chen, Yuanmou,Xu, Xiaoling,Zhang, Xu,Yu, Yue,Yu, Peng,Hua, Erbing
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p. 2092 - 2098
(2014/06/09)
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- SuFEx-based synthesis of polysulfates
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High-molecular-weight polysulfates are readily formed from aromatic bis(silyl ethers) and bis(fluorosulfates) in the presence of a base catalyst. The reaction is fast and proceeds well under neat conditions or in solvents, such as dimethyl formamide or N-methylpyrrolidone, to provide the desired polymers in nearly quantitative yield. These polymers are more resistant to chemical degradation than their polycarbonate analogues and exhibit excellent mechanical, optical, and oxygen-barrier properties. High-molecular-weight polysulfates are readily formed from aromatic bis(silyl ethers) and bis(fluorosulfates) in the presence of a base catalyst. The polymers were obtained in nearly quantitative yield under neat conditions, they are more resistant to chemical degradation than their polycarbonate analogues and exhibit excellent mechanical, optical, and oxygen-barrier properties. BPA=bisphenol A.
- Dong, Jiajia,Sharpless, K. Barry,Kwisnek, Luke,Oakdale, James S.,Fokin, Valery V.
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supporting information
p. 9466 - 9470
(2014/11/07)
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- A new synthesis for acacetin, chrysoeriol, diosmetin, tricin and other hydroxylated flavones by modified Baker-Venkataraman transformation
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Baker-Venkataraman (BV) rearrangement is the method of choice for the synthesis of flavones. The major limitation of BV is that it requires extensive protections and deprotections of hydroxyl groups which make the process lengthy and cumbersome. In the present study, a three step efficient method has been developed using simple protecting groups and easily available starting materials. New syntheses for acacetin, chrysoeriol, diosmetin, tricin and other hydroxylated flavones are described.
- Pandurangan
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supporting information
p. 225 - 229
(2014/05/20)
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- Synthesis and Quantitative Structure-Activity Relationships of Selective BCRP Inhibitors
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The breast cancer resistance protein (BCRP/ABCG2) is a member of the ABC transporter superfamily. This protein has a number of physiological functions, including protection of the human body from xenobiotics. The overexpression of BCRP in certain tumor cell lines causes cross-resistance against various drugs used in chemotherapeutic treatment. In a previous work we showed that a new class of compounds derived from XR9576 (tariquidar) selectively inhibits BCRP. In this work we synthesized more members of this class, with modification on the second and third aromatic rings. The inhibitory activities against BCRP and P-gp were assayed using a Hoechst 33342 assay for BCRP and a calcein AM assay for P-gp. Finally, quantitative structure-activity relationships for both aromatic rings were established. The results obtained show the importance of the electron density on the third aromatic ring, influenced by substituents, pointing to interactions with aromatic residues of the protein binding site. In the second aromatic ring the activity of compounds is influenced by the steric volume of the substituents.
- Marighetti, Federico,Steggemann, Kerstin,Hanl, Markus,Wiese, Michael
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p. 125 - 135
(2013/02/26)
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- 3D-QSAR-assisted design, synthesis, and evaluation of novobiocin analogues
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Hsp90 is an attractive therapeutic target for the treatment of cancer. Extensive structural modifications to novobiocin, the first Hsp90 C-terminal inhibitor discovered, have produced a library of novobiocin analogues and revealed some structure-activity relationships. On the basis of the most potent novobiocin analogues generated from prior studies, a three-dimensional quantitative structure-activity (3D QSAR) model was built. In addition, a new set of novobiocin analogues containing various structural features supported by the 3D QSAR model were synthesized and evaluated against two breast cancer cell lines. Several new inhibitors produced antiproliferative activity at midnanomolar concentrations, which results through Hsp90 inhibition.
- Zhao, Huiping,Moroni, Elisabetta,Yan, Bin,Colombo, Giorgio,Blagg, Brian S. J.
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supporting information
p. 57 - 62
(2013/02/26)
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- Synthesis of new metallomesogens based on 3-ketoesters
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Ethyl 3-(4-hydroxyphenyl)-3-ketopropionate was synthesized by acylation of acetoacetic ester with 4-acetoxybenzoyl chloride, followed by cleavage of aroylacetoacetic ester and hydrolysis of the protecting acetate group. Further esterification of the pheno
- Kovganko,Kovganko
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p. 1556 - 1562
(2013/10/22)
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- Aurora isoform selectivity: Design and synthesis of imidazo[4,5- B ]pyridine derivatives as highly selective inhibitors of aurora-A kinase in cells
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Aurora-A differs from Aurora-B/C at three positions in the ATP-binding pocket (L215, T217, and R220). Exploiting these differences, crystal structures of ligand-Aurora protein interactions formed the basis of a design principle for imidazo[4,5-b]pyridine-
- Bavetsias, Vassilios,Faisal, Amir,Crumpler, Simon,Brown, Nathan,Kosmopoulou, Magda,Joshi, Amar,Atrash, Butrus,Pérez-Fuertes, Yolanda,Schmitt, Jessica A.,Boxall, Katherine J.,Burke, Rosemary,Sun, Chongbo,Avery, Sian,Bush, Katherine,Henley, Alan,Raynaud, Florence I.,Workman, Paul,Bayliss, Richard,Linardopoulos, Spiros,Blagg, Julian
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supporting information
p. 9122 - 9135
(2014/01/06)
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- Preparation of monolignol γ-acetate, γ-p-hydroxycinnamate, and γ-p-hydroxybenzoate conjugates: Selective deacylation of phenolic acetates with hydrazine acetate
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We report here a reliable and facile synthesis of a range of monolignol γ-p-hydroxycinnamate (including p-coumarate, ferulate, and caffeate), γ-acetate, and γ-p-hydroxybenzoate conjugates, many not previously reported, that are either putative intermediat
- Zhu, Yimin,Regner, Matthew,Lu, Fachuang,Kim, Hoon,Mohammadi, Allison,Pearson, Timothy J.,Ralph, John
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p. 21964 - 21971
(2013/11/06)
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- CONFORMATIONALLY CONSTRAINED, FULLY SYNTHETIC MACROCYCLIC COMPOUNDS
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Conformationally restricted, spatially defined 12-30 membered macrocyclic ring systems of type (I) are constituted by three distinct building blocks: an aromatic template a, a conformation modulator b and a spacer moiety c as detailed in the description and the claims. Macrocycles of type (I) are readily manufactured by parallel synthesis or combinatorial chemistry. They are designed to interact with specific biological targets. In particular, they show agonistic or antagonistic activity on the motilin receptor (MR receptor), on the serotonin receptor of subtype 5-HT2B (5-HT2B receptor), and on the prostaglandin F2?receptor (FP receptor). They are thus potentially useful for the treatment of hypomotility disorders of the gastrointestinal tract such as diabetic gastroparesis and constipation type irritable bowl syndrome; of CNS related diseases like migraine, schizophrenia, psychosis or depression; of ocular hypertension such as associated with glaucoma and preterm labour.
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Page/Page column 122; 246
(2012/08/27)
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- CONFORMATIONALLY CONSTRAINED, FULLY SYNTHETIC MACROCYCLIC COMPOUNDS
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Conformationally restricted, spatially defined 12-30 membered macrocyclic ring systems of formulae Ia and Ib are constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. These macrocycles Ia and Ib are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being the agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), ion channels and signal transduction pathways. In particular, these macrocycles act as antagonists of the motilin receptor, the FP receptor and the purinergic receptors P2Y1, as modulators of the serotonin receptor of subtype 5-HT2B, as blockers of the voltage-gated potassium channel Kv1.3 and as inhibitors of the β-catenin-dependent “canonical” Wnt pathway. Thus they are showing great potential as medicaments for a variety of diseases.
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Page/Page column 122
(2012/11/07)
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