- A 3D MOF showing unprecedented solvent-induced single-crystal-to-single-crystal transformation and excellent CO2 adsorption selectivity at room temperature
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A water stable porous 3D metal-organic framework, [Cu3L2(μ3-OH)2(μ2-H2O)]·2DMA (1, mother crystal, H2L = 2,2′-dinitrobiphenyl-4,4′-dicarboxylic acid, DMA = N,N-dimethylacetamide), shows unprecedented irreversible solvent-induced substitutions of bridging aqua ligands and guest-exchanges in single-crystal-to-single-crystal (SCSC) transformations at room temperature (RT), producing quantitatively three daughter crystals, [Cu3L2(μ3-OH)2]·2S (2: 2A, S = acetone; 2B, S = 2-propanol; 2C, S = 2-butanol), which exhibit reversible interconversion by guest-exchanges at RT in SCSC transformations. MOF 1 shows excellent separation selectivity (128) of CO2/N2 at RT and is a better sorbent of micro-solid-phase extraction (μ-SPE) than currently known benchmark ZIF-8.
- Qin, Tao,Gong, Jun,Ma, Junhan,Wang, Xin,Wang, Yonghua,Xu, Yan,Shen, Xuan,Zhu, Dunru
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Read Online
- Creative Construction of a Series of Chiral 3D Indium-Organic Frameworks with a umy Topology
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Using 2,2′-R2-biphenyl-4,4′-dicarboxylic acid to bind with a cis-[InO4(μ2-OH)2] octahedron, three novel chiral 3D indium-organic frameworks, [In(μ2-OH)L] [1, L1, R = N(CH3)2; 2, L2, R = OCH3; 3, L3, R = CH3], have been hydrothermally synthesized without chiral reagents. Crystal structure analyses reveal that 1-3 show an unprecedented 4-connected umy topology with the Schl?fli symbol (42·64). 1 exhibits high water stability and good sorption selectivity of CO2 over N2, while 3 displays high C2H2, C2H4, and C2H6 uptake capacity at 273 K.
- He, Xin,Wang, Xin,Xiao, Tianyu,Zhang, Shunlin,Zhu, Dunru
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Read Online
- Beta-carboboline GSK3beta/DYRK1A dual inhibitor and preparation method thereof and application of beta-carboboline GSK3beta/DYRK1A dual inhibitor in resisting Alzheimer's disease
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The invention discloses a beta-carboline GSK3beta/DYRK1A dual inhibitor as shown in a general formula I, a preparation method of the beta-carboline GSK3beta/DYRK1A dual inhibitor and application of the beta-carboline GSK3beta/DYRK1A dual inhibitor in resi
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Paragraph 0195-0198
(2021/07/08)
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- Design, synthesis and biological evaluation of harmine derivatives as potent GSK-3β/DYRK1A dual inhibitors for the treatment of Alzheimer's disease
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Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease, characterized by irreversible cognitive impairment, memory loss and behavioral disturbances, ultimately leading to death. Glycogen synthase kinase 3β (GSK-3β) and dual-specificity tyrosine phosphorylation regulated kinase1A (DYRK1A) have gained a lot of attention for its role in tau pathology. To search for potential dual GSK-3β/DYRK1A inhibitors, we focused on harmine, a natural β-carboline alkaloid, which has been extensively studied for its various biological effects on the prevention of AD. In this study, a new series of harmine derivatives were designed, synthesized and evaluated as dual GSK-3β/DYRK1A inhibitors for their multiple biological activities. The in vitro results indicated that most of them displayed promising activity against GSK-3β and DYRK1A. Among them, compound ZDWX-25 showed potent inhibitory effects on GSK-3β and DYRK1A with IC50 values of 71 and 103 nM, respectively. Molecular modelling and kinetic studies verified that ZDWX-25 could interact with the ATP binding pocket of GSK-3β and DYRK1A. Western blot analysis revealed that ZDWX-25 inhibited hyperphosphorylation of tau protein in okadaic acid (OKA)-induced SH-SY5Y cells. In addition, ZDWX-25 showed good blood-brain barrier penetrability in vitro. More importantly, ZDWX-25 could ameliorate the impaired learning and memory in APP/PS1/Tau transgenic mice. These results indicated that the harmine-based compounds could be served as promising dual-targeted candidates for AD.
- Liu, Wenwu,Liu, Xin,Tian, Liting,Gao, Yaping,Liu, Wenjie,Chen, Huanhua,Jiang, Xiaowen,Xu, Zihua,Ding, Huaiwei,Zhao, Qingchun
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- Synthesis of multifunctional metal-organic frameworks and tuning the functionalities with pendant ligands
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A series of multifunctional metal-organic frameworks (MOFs), SNU-170-SNU-176, has been synthesized using ligands, in which various functional pendants such as -NH2, -SMe, -OMe, -OEt, -OPr, and -OBu are attached to the phenyl ring of 4-(2-carboxyvinyl)benz
- Prasad, Thazhe Kootteri,Suh, Myunghyun Paik
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supporting information
p. 15034 - 15040
(2020/11/11)
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- New Dual CK2/HDAC1 Inhibitors with Nanomolar Inhibitory Activity against Both Enzymes
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Four potent CK2 inhibitors derived from CX-4945 are described. They also provided nanomolar activity against HDAC1, therefore having promising utility as dual-target agents for cancer. The linker length between the hydroxamic acid and the CX-4945 scaffold plays an important role in dictating balanced activity against the targeted enzymes. The seven-carbon linker (compound 15c) was optimal for inhibition of both CK2 and HDAC1. Remarkably, 15c showed 3.0 and 3.5 times higher inhibitory activity than the reference compounds CX-4945 (against CK2) and SAHA (against HDAC1), respectively. Compound 15c exhibited micromolar activity in cell-based cytotoxic assays against multiple cell lines.
- Coderch, Claire,De Pascual-Teresa, Beatriz,Ortín, Irene,Ramos, Ana,Rangasamy, Loganathan,Zapico, José María
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supporting information
p. 713 - 719
(2020/07/14)
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- Design and Synthesis of N1-Modified Imidazoquinoline Agonists for Selective Activation of Toll-like Receptors 7 and 8
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A series of N1-modified imidazoquinolines were synthesized and screened for Toll-like receptors (TLR) 7 and 8 activities to identify recognition elements that confer high affinity binding and selectivity. These receptors are key targets in the development of immunomodulatory agents that signal the NF-κB mediated transcription of pro-inflammatory chemokines and cytokines. Results are presented showing both TLR7/8 activations are highly correlated to N1-substitution, with TLR8 selectivity achieved through inclusion of an ethyl-, propyl-, or butylamino group at this position. While the structure-activity relationship analysis indicates TLR7 activity is less sensitive to N1-modification, extension of the aminoalkyl chain length to pentyl and p-methylbenzyl elicited high affinity TLR7 binding. Cytokine profiles are also reported that show the pure TLR8 agonist [4-amino-2-butyl-1-(2-aminoethyl)-7-methoxycarbonyl-1H-imidazo[4,5-c]quinoline] induces higher levels of IL-1β, IL-12, and IFNγ when compared with TLR7 selective or mixed TLR7/8 agonists. The results are consistent with previous work suggesting TLR8 agonists are Th1 polarizing and may help promote cell-mediated immunity.
- Larson, Peter,Kucaba, Tamara A.,Xiong, Zhengming,Olin, Michael,Griffith, Thomas S.,Ferguson, David M.
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supporting information
p. 1148 - 1152
(2017/11/15)
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- TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF
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The present invention is directed to bicyclic heteroaryl benzamide compounds of formulas (I) which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence are useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.
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Page/Page column 74
(2016/10/31)
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- FUSED TETRA OR PENTA-CYCLIC PYRIDOPHTHALAZINONES AS PARP INHIBITORS
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Provided are certain fused tetra or penta-cyclic compounds and salts thereof, compositions thereof, and methods of use thereof.
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Paragraph 0244
(2015/02/18)
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- TrkA KINASE INHIBITORS,COMPOSITIONS AND METHODS THEREOF
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The present invention is directed to substituted five membered heteroaryl benzamide compounds compounds of formula (I), which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence are useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.
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Page/Page column 56
(2015/12/08)
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- TRKA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF
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The present invention is directed to six membered heteroaryl benzamide compounds of formula (I), which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence are useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.
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Page/Page column 104
(2015/12/30)
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- TrkA KINASE INHIBITORS,COMPOSITIONS AND METHODS THEREOF
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The present invention is directed to a bicyclic heteroaryl benzamide compounds of formula(I) which are tropomyosin-related kinase(Trk)family protein kinase inhibitors, and hence are useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF)receptor TrkA.
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Page/Page column 46
(2016/03/04)
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- Fragment-based design of 3-aminopyridine-derived amides as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT)
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The fragment-based identification of two novel and potent biochemical inhibitors of the nicotinamide phosphoribosyltransferase (NAMPT) enzyme is described. These compounds (51 and 63) incorporate an amide moiety derived from 3-aminopyridine, and are thus structurally distinct from other known anti-NAMPT agents. Each exhibits potent inhibition of NAMPT biochemical activity (IC 50 = 19 and 15 nM, respectively) as well as robust antiproliferative properties in A2780 cell culture experiments (IC50 = 121 and 99 nM, respectively). However, additional biological studies indicate that only inhibitor 51 exerts its A2780 cell culture effects via a NAMPT-mediated mechanism. The crystal structures of both 51 and 63 in complex with NAMPT are also independently described.
- Dragovich, Peter S.,Zhao, Guiling,Baumeister, Timm,Bravo, Brandon,Giannetti, Anthony M.,Ho, Yen-Ching,Hua, Rongbao,Li, Guangkun,Liang, Xiaorong,Ma, Xiaolei,O'Brien, Thomas,Oh, Angela,Skelton, Nicholas J.,Wang, Chengcheng,Wang, Weiru,Wang, Yunli,Xiao, Yang,Yuen, Po-Wai,Zak, Mark,Zhao, Qiang,Zheng, Xiaozhang
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p. 954 - 962
(2014/02/14)
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- FUSED TETRA OR PENTA-CYCLIC PYRIDOPHTHALAZINONES AS PARP INHIBITORS
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Provided are certain fused tetra or penta-cyclic compounds and salts thereof, compositions thereof, and methods of use thereof.
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Page/Page column 40; 41
(2013/07/19)
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