- Optically sensed, molecular shuttles driven by acid-base chemistry
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A pair of bistable [2]rotaxane, molecular shuttles were prepared that combine 1,2-bis(pyridinium)ethane and benzylanilinium recognition sites; acid-base controlled shuttling of DB24C8 was accompanied by a change in colour and/or fluorescence intensity. The Royal Society of Chemistry.
- Vella, Sarah J.,Tiburcio, Jorge,Loeb, Stephen J.
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Read Online
- Functionalized naphthalenediimide based supramolecular charge-transfer complexesviaself-assembly and their photophysical properties
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We report here the design and syntheses of a naphthalenediimide (NDI)-N functionalized organic fluorophore,1, and its supramolecular CT complexes [(1·2H)2+·(PA?)2] (2) and [(1·2H)2+·(3,5-DNSA?)2] (3), self-assembled from1as an electron acceptor (A) and picric acid (PA) or 3,5-dinitrosalicylic acid (3,5-DNSA) as a donor (D), with a very large Stokes shift (>170 nm) and significant fluorescence lifetime (~1.55 ns). NDI is functionalized with phenylpyridyl units (chromophore) to extend the π-conjugation and thus provide a suitable platform for strong C-H-π and π?π stacking interactions, which are the prime requirements for any compound to be used as a fluorescent probe. The organic fluorophore,1, and its supramolecular CT complexes2and3exhibit decent electronic properties as suggested by DFT, cyclic voltammetry, and fluorescence studies. Moreover, compounds1-3were also exploited as fluorescent probes for cell imaging under normal cell isolation and with time-bound exposure.
- Rani, Pooja,Husain, Ahmad,Shukla, Ananya,Singla, Neha,Srivastava, Ankit Kumar,Kumar, Gulshan,Bhasin,Kumar, Girijesh
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- Electron transfer within self-assembling cyclic tetramers using chlorophyll-based donor-acceptor building blocks
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The synthesis and photoinduced charge transfer properties of a series of Chl-based donor-acceptor triad building blocks that self-assemble into cyclic tetramers are reported. Chlorophyll a was converted into zinc methyl 3-ethylpyrochlorophyllide a (Chl) and then further modified at its 20-position to covalently attach a pyromellitimide (PI) acceptor bearing a pyridine ligand and one or two naphthalene-1,8:4,5-bis(dicarboximide) (NDI) secondary electron acceptors to give Chl-PI-NDI and Chl-PI-NDI2. The pyridine ligand within each ambident triad enables intermolecular Chl metal-ligand coordination in dry toluene, which results in the formation of cyclic tetramers in solution, as determined using small- and wide-angle X-ray scattering at a synchrotron source. Femtosecond and nanosecond transient absorption spectroscopy of the monomers in toluene-1% pyridine and the cyclic tetramers in toluene shows that the selective photoexcitation of Chl results in intramolecular electron transfer from 1*Chl to PI to form Chl+?-PI -?-NDI and Chl+?-PI-?-NDI 2. This initial charge separation is followed by a rapid charge shift from PI-? to NDI and subsequent charge recombination of Chl+?-PI-NDI-? and Chl+?-PI- (NDI)NDI-? on a 5-30 ns time scale. Charge recombination in the Chl-PI-NDI2 cyclic tetramer (τCR = 30 ± 1 ns in toluene) is slower by a factor of 3 relative to the monomeric building blocks (τCR = 10 ± 1 ns in toluene-1% pyridine). This indicates that the self-assembly of these building blocks into the cyclic tetramers alters their structures in a way that lengthens their charge separation lifetimes, which is an advantageous strategy for artificial photosynthetic systems.
- Gunderson, Victoria L.,Smeigh, Amanda L.,Kim, Chul Hoon,Co, Dick T.,Wasielewski, Michael R.
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Read Online
- NOVEL HYDRAZONE DERIVATIVE WITH ARYL OR HETEROARYL GROUP SUBSTITUTED AT TERMINAL AMINE GROUP THEREOF AND USE THEREOF
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The present invention relates to novel hydrazone derivatives in which a terminal amine group is substituted with an aryl group or a heteroaryl group, and uses thereof.
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Paragraph 0069; 0099
(2021/11/04)
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- Novel hydrazone derivatives comprising aryl or heteroaryl group substituted at terminal amine and use thereof
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The present invention relates to novel hydrazone derivatives with an aryl or heteroaryl group substituted at a terminal amine group thereof and a use thereof.
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Paragraph 0325; 0327; 0328; 0472; 0474; 0475
(2020/08/28)
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- RHO-ASSOCIATED PROTEIN KINASE INHIBITOR, PHARMACEUTICAL COMPOSITION COMPRISING THE SAME, AS WELL AS PREPARATION METHOD AND USE THEREOF
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The present invention relates to a Rho-associated protein kinase inhibitor of Formula (I), a pharmaceutical composition comprising the same, a preparation method thereof, and use thereof for the prevention or treatment of a disease mediated by the Rho-associated protein kinase (ROCK).
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Paragraph 0136; 0138
(2019/01/11)
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- RHO-ASSOCIATED PROTEIN KINASE INHIBITOR, PHARMACEUTICAL COMPOSITION COMPRISING THE SAME, AS WELL AS PREPARATION METHOD AND USE THEREOF
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The present invention relates to a Rho-associated protein kinase inhibitor of Formula (I), a pharmaceutical composition comprising the same, a preparation method thereof, and use thereof for the prevention or treatment of a disease mediated by the Rho-associated protein kinase (ROCK).
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Paragraph 0134; 0136
(2019/01/11)
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- Microballs Containing Ni(0)Pd(0) Nanoparticles for Highly Selective Micellar Catalysis in Water
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Both Ni(0) complexes and nanoparticles (NPs) are unstable in water, which poses a significant hindrance to their application in aqueous synthetic catalysis. To overcome these barriers, ligated Ni(0) nanoparticles (diameter 1 nm) containing a minimum amount of Pd(0) in the microballs formed of amphiphile PS-750-M are developed and applied in the highly selective carbamate cleavage. Selectivity and functional group tolerance are thoroughly investigated. Control experiments revealed the importance of an individual component of the nanocatalyst. Use of our proline-based amphiphile PS-750-M is critical for achieving microball architecture, the stability of nanoparticles, and desired catalytic activity. Once formed, microballs can be isolated and stored at ambient temperature. Catalyst is thoroughly characterized by X-ray photoelectron spectroscopy, scanning electron microscopy, high-resolution transmission electron microscopy, thermogravimetric analysis, infrared, and cyclic voltammetry. For selective catalysis, zero oxidation state of both Ni and Pd is crucial. On the basis of catalyst characterization and control experiments, the plausible reaction mechanism is proposed.
- Bihani, Manisha,Bora, Pranjal P.,Nachtegaal, Maarten,Jasinski, Jacek B.,Plummer, Scott,Gallou, Fabrice,Handa, Sachin
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p. 7520 - 7526
(2019/08/15)
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- Triazole naphthoquinone connected aromatic (heterocyclic) ring derivative
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The invention belongs to the field of chemical medicine, particularly relates to a micromolecule capable of resisting malignant tumor, acute leukemia and arthritis, multiple sclerosis and immunological rejection and a preparation and application of the mi
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Paragraph 0057; 0058; 0059
(2018/10/01)
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- The synthesis of a rigid conjugated viologen and its cucurbituril pseudorotaxanes
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A linear viologen (bis[4-(4-pyridinyl)phenyl] viologen, BPPV) characterized by a fully-conjugated structure was synthesized through Zinke reaction. BPPV consists of a unique linear sexiaryl structure and is apt to be encapsulated by cucurbit[n]uril (CB[n]
- Song, Yingfeng,Huang, Xinghua,Hua, Haojie,Wang, Qiaochun
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p. 229 - 235
(2016/11/09)
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- Synthesis and characterization of the first inhibitor of: N -acylphosphatidylethanolamine phospholipase D (NAPE-PLD)
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N-Acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is a membrane-associated zinc enzyme that catalyzes the hydrolysis of N-acylphosphatidylethanolamines (NAPEs) into fatty acid ethanolamides (FAEs). Here, we describe the identification of the first small-molecule NAPE-PLD inhibitor, the quinazoline sulfonamide derivative 2,4-dioxo-N-[4-(4-pyridyl)phenyl]-1H-quinazoline-6-sulfonamide, ARN19874.
- Castellani, Beatrice,Diamanti, Eleonora,Pizzirani, Daniela,Tardia, Piero,Maccesi, Martina,Realini, Natalia,Magotti, Paola,Garau, Gianpiero,Bakkum, Thomas,Rivara, Silvia,Mor, Marco,Piomelli, Daniele
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supporting information
p. 12814 - 12817
(2017/12/06)
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- Discovery of lipoic acid-4-phenyl-1: H -pyrazole hybrids as novel bifunctional ROCK inhibitors with antioxidant activity
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A series of lipoic acid (LA) and 4-phenyl-1H-pyrazole hybrids as bifunctional Rho-associated kinase (ROCK) inhibitors were designed, synthesized and evaluated. Compound 15 is identified to be a novel potent bifunctional ROCK inhibitor with antioxidant activity and neuroprotection.
- Tu, Ya-Lin,Chen, Qiu-He,Wang, Sheng-Nan,Uri, Asko,Yang, Xiao-Hong,Chu, Jia-Qi,Chen, Jing-Kao,Luo, Bing-Ling,Chen, Xiao-Hong,Wen, Shi-Jun,Pi, Rong-Biao
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p. 58516 - 58520
(2016/07/07)
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- Compounds for treating degenerative disease of central nervous system and application of compounds
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The invention relates to compounds for treating degenerative disease of a central nervous system, pharmaceutical composition and an application of the compounds. The compounds have a structure shown in a formula (I) and can be used as a ROCK inhibitor, and appropriate pharmaceutical dosage forms prepared from the compounds are used for treating the neurodegenerative disease.
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Paragraph 0017-0018
(2017/07/22)
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- Synthesis and methemoglobinemia-inducing properties of benzocaine isosteres designed as humane rodenticides
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A number of isosteres (oxadiazoles, thiadiazoles, tetrazoles and diazines) of benzocaine were prepared and evaluated for their capacity to induce methemoglobinemia - with a view to their possible application as humane pest control agents. It was found that an optimal lipophilicity for the formation of methemoglobin (metHb) in vitro existed within each series, with 1,2,4-oxadiazole 3 (metHb% = 61.0 ± 3.6) and 1,3,4-oxadiazole 10 (metHb% = 52.4 ± 0.9) demonstrating the greatest activity. Of the 5 candidates (compounds 3, 10, 11, 13 and 23) evaluated in vivo, failure to induce a lethal end-point at doses of 120 mg/kg was observed in all cases. Inadequate metabolic stability, particularly towards hepatic enzymes such as the CYPs, was postulated as one reason for their failure.
- Conole, Daniel,Beck, Thorsten M.,Jay-Smith, Morgan,Tingle, Malcolm D.,Eason, Charles T.,Brimble, Margaret A.,Rennison, David
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p. 2220 - 2235
(2014/04/17)
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- INHIBITORS OF RHO ASSOCIATED PROTEIN KINASES (ROCK) AND METHODS OF USE
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Compounds and compositions having activity as inhibitors of Rho-associated proteinkinases (ROCKs), and methods of making and using the subject compounds are disclosed.
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Page/Page column 45
(2013/08/15)
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- PYRAZINE KINASE INHIBITORS
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Provided are pyrazine compounds for inhibiting of Syk kinase, intermediates used in making such compounds, methods for their preparation, pharmaceutical compositions thereof, methods for inhibition Syk kinase activity, and methods for treating conditions mediated at least in part by Syk kinase activity.
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Paragraph 0360
(2013/06/04)
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- Fragment-based and structure-guided discovery and optimization of Rho kinase inhibitors
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Using high concentration biochemical assays and fragment-based screening assisted by structure-guided design, we discovered a novel class of Rho-kinase inhibitors. Compound 18 was equipotent for ROCK1 (IC50 = 650 nM) and ROCK2 (IC50 = 670 nM), whereas compound 24 was more selective for ROCK2 (IC50 = 100 nM) over ROCK1 (IC50 = 1690 nM). The crystal structure of the compound 18-ROCK1 complex revealed that 18 is a type 1 inhibitor that binds the hinge region in the ATP binding site. Compounds 18 and 24 inhibited potently the phosphorylation of the ROCK substrate MLC2 in intact human breast cancer cells.
- Li, Rongshi,Martin, Mathew P.,Liu, Yan,Wang, Binglin,Patel, Ronil A.,Zhu, Jin-Yi,Sun, Nan,Pireddu, Roberta,Lawrence, Nicholas J.,Li, Jiannong,Haura, Eric B.,Sung, Shen-Shu,Guida, Wayne C.,Schonbrunn, Ernst,Sebti, Said M.
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supporting information; experimental part
p. 2474 - 2478
(2012/05/20)
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- UREAS AS FACTOR XA INHIBITORS
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The present invention is directed to compounds represented by Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, and prodrugs thereof which are inhibitors of Factor Xa. The present invention is also directed to and intermediates used in making such compounds, pharmaceutical compositions containing such compounds, methods to prevent or treat a number of conditions characterized by undesired thrombosis and methods of inhibiting the coagulation of a blood sample.
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(2010/11/08)
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- 4-Aminothiazole derivatives, their preparation and their use as inhibitors of cyclin-dependent kinases
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This invention is directed to aminothiazole compounds of formula (I) wherein R1 is a substituted or unsubstituted group selected from : C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; C1-6-alkoxyl; C1-6-alcohol; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; carbonyl; ether; (C1-6-alkyl)-carbonyl; (C1-6-alkyl)-aryl; (C1-6-alkyl)-cycloalkyl; (C1-6-alkyl)-(C1-6-alkoxyl); aryl-(C1-6-alkoxyl); thioether; thiol; and sulfonyl; wherein when R1 is substituted, each substituent independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol, thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; ester; oxygen; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; or carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; and R2 is a carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, ring structure having a substituent at the position adjacent to the point of attachment, which ring structure is optionally further substituted, where each substituent of R2 independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol; thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; ester; oxygen; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; or carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; or a pharmaceutically acceptable salt of a compound of formula (I), or a prodrug or pharmaceutically active metabolite of a compound of formula (I) or pharmaceutically acceptable salt thereof, for inhibiting cyclin-dependent kinases (CDKs), such as CDK1, CDK2, CDK4, and CDK6. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds and to methods of treating malignancies and other disorders by administering effective amounts of such compounds.
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Example C(122)
(2010/11/29)
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- Biarylcarbamoylindolines are novel and selective 5-HT(2C) receptor inverse agonists: Identification of 5-methyl-1-[[2-[(2-methyl-3- pyridyl)oxy]5-pyridyl]carbamoyl]-6-trifluoromethylindoline (SB-243213) as a potential antidepressant/anxiolytic agent
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The evolution, synthesis, and biological activity of a novel series of 5-HT(2C) receptor inverse agonists are reported. Biarylcarbamoylindolines have been identified with excellent 5-HT(2C) affinity and selectivity over 5- HT(2A) receptors. In addition, (pyridyloxypyridyl)carbamoylindolines have been discovered with additional selectivity over the closely related 5-HT(2B) receptor. Compounds from this series are inverse agonists at the human cloned 5-HT(2C) receptor, completely abolishing basal activity in a functional assay. The new series have reduced P450 inhibitory liability compared to a previously described series of 1-(3-pyridylcarbamoyl)indolines (Bromidge et al. J. Med. Chem. 1998, 41, 1598) from which they evolved. Compounds from this series showed excellent oral activity in a rat mCPP hypolocomotion model and in animal models of anxiety. On the basis of their favorable biological profile, 32 (SB-228357) and 40 (SB-243213) have been selected for further evaluation to determine their therapeutic potential for the treatment of CNS disorders such as depression and anxiety.
- Bromidge, Steven M.,Dabbs, Steven,Davies, David T.,Davies, Susannah,Duckworth, D. Malcolm,Forbes, Ian T.,Gaster, Laramie M.,Ham, Peter,Jones, Graham E.,King, Frank D.,Mulholland, Keith R.,Saunders, Damian V.,Wyman, Paul A.,Blaney, Frank E.,Clarke, Stephen E.,Blackburn, Thomas P.,Holland, Vicky,Kennett, Guy A.,Lightowler, Sean,Middlemiss, Derek N.,Trail, Brenda,Riley, Graham J.,Wood, Martyn D.
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p. 1123 - 1134
(2007/10/03)
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- Differentiation between partial agonists and neutral 5-HT(1B) antagonists by chemical modulation of 3-[3-(N,N-dimethylamino)propyl]-4- hydroxy-N-[4-(pyridin-4-yl)phenyl]benzamide (GR-55562)
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The synthesis and binding affinity at cloned h5-HT(1B), h5-HT(1D), and h5-HT(1A) receptors of 3-[3-(N,N-dimethylamino)propyl]-4-hydroxy-N-[4- (pyridin-4-yl)phenyl]benzamide (2, GR-55562) and four O-methylated analogs are described. The functional activity of these compounds was determined at the h5-HT(1B) receptor using a [35S]GTPγS binding assay. The four analogs have been prepared in order to evaluate the influence of the alkylamino side chain conformation on binding and intrinsic activity. Whereas 2 and its derivatives display a similar binding affinity profile, major differences arise from analysis of the intrinsic activity data at h5-HT(1B) receptors. The O-methylated analog of 2, 3-[3-(N,N-dimethylamino)propyl]-4-methoxy-N- [4-(pyridin-4-yl)phenyl]benzamide (3a), and the (1Z)-3-(N,N- dimethylamino)prop-1-enyl derivative (3c) act as neutral and potent antagonists (in a similar way to 2), while the 3-(N,N-dimethylamino)-prop-1- ynyl (3b) and (1E)-3-(N,N-dimethylamino)prop-1-enyl (3d) analogs display nonnegligible agonist activity. Molecular modeling studies show that, when the common triaryl portions of the molecules are overlapped, the partial agonists and the neutral antagonists differ by a near-orthogonal orientation of the NH+ projection to the hydrogen-bond receptor site.
- Lamothe, Marie,Pauwels, Petrus J.,Belliard, Karine,Schambel, Philippe,Halazy, Serge
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p. 3542 - 3550
(2007/10/03)
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- Photochemistry of Intramolecular Charge Transfer Excited States in Donor-Acceptor-Substituted Diamines
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The photochemistry and photophysics of 1,2-diamines C5H10NCHPhCHPhNHC6H4R (1, R=CN, and 2, R=4-pyridyl) have been examined.These compounds display a strong absorption band in the near-UV which is due to intramolecular charge transfer from the secondary amine group to the 4-cyanophenyl or (4-pyridyl)phenyl acceptor unit.Photoexcitation into this absorption band leads to moderately intense fluorescence from the 1LE state of the charge transfer chromophore and to homolytic bond fragmentation across the 1,2 C-C bond with moderate quantum efficiency.Detailed photochemical and photophysical studies reveal that the bond fragmentation reaction ensues from a second intramolecular charge transfer excited state (denoted 1CT) which is based on electron transfer from the tertiary piperidine nitrogen to the 4-cyanophenyl or (4-pyridyl)phenyl unit.Photochemical product analysis reveals that erythro -> threo (or threo -> erythro) isomerization occurs under both argon-degassed and air-saturated conditions.This observation indicates that recombination of the radicals formed by bond fragmentation occurs, both within the geminate pair and between free radicals that have escaped the solvent cage.Analysis of fluorescence, transient absorption, and steady-state photochemical kinetics data indicates that (1) internal conversion from the 1LE state to the 1CT state by intramolecular electron transfer occurs with k>/=109 s-1 in all of the diamines; (2) bond fragmentation within the 1CT state occurs with k>/=108 s-1 in each of the diamines; (3) bond fragmentation may be faster in erythro-1 than in threo-1.
- Wang, Yingsheng,Schanze, Kirk S.
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p. 6876 - 6888
(2007/10/02)
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- PROPERTIES OF THE LIQUID CRYSTALS FORMED BY CERTAIN 4-(2 prime -PYRIDYL)PHENYL AND 4-(4 prime -PYRIDYL)PHENYL 4 double prime -N-ALKOXYBENZOATES.
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Nine members of each of two homologous series of esters, the 4-(2 prime -pyridyl)phenyl and the 4-(4 prime -pyridyl)phenyl 4 double prime -n-alkoxybenzoates, were prepared and their liquid crystal transition temperatures measured. Both homologous series w
- Byron,Lacey,Wilson
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p. 103 - 114
(2007/10/02)
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