- NOVEL MORPHOLINE DERIVATIVE OR SALT THEREOF
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There is provided a morpholine derivative represented by General Formula [1A] or a salt thereof. (In the formula, a ring A represents a ring represented by General Formula [I]; * represents a bonding position; Z2 represents CH or the like; Z1 represents CR6 or the like; R6 represents a hydrogen atom or the like; X1 represents CHR7 or the like; R7 represents a hydrogen atom or the like; X2 represents CH2 or the like; R1 and R2 are the same as or different from each other, and each of R1 and R2 represents a hydrogen atom or the like; R3, R4, and R5 are the same as or different from each other, and each of R3, R4, and R5 represents a hydrogen atom, NRaRb, or the like; and each of Ra and Rb represents a hydrogen atom, a C1-8 alkyl group which may have a substituent, or the like.)
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Paragraph 0943; 1195; 1198-1200
(2016/07/05)
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- Effects of structural modifications on the metal binding, anti-amyloid activity, and cholinesterase inhibitory activity of chalcones
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As the number of individuals affected with Alzheimer's disease (AD) increases and the availability of drugs for AD treatment remains limited, the need to develop effective therapeutics for AD becomes more and more pressing. Strategies currently pursued include inhibiting acetylcholinesterase (AChE) and targeting amyloid-β (Aβ) peptides and metal-Aβ complexes. This work presents the design, synthesis, and biochemical evaluation of a series of chalcones, and assesses the relationship between their structures and their ability to bind metal ions and/or Aβ species, and inhibit AChE/BChE activity. Several chalcones were found to exhibit potent disaggregation of pre-formed N-biotinyl Aβ1-42 (bioAβ42) aggregates in vitro in the absence and presence of Cu2+/Zn2+, while others were effective at inhibiting the action of AChE.
- Fosso, Marina Y.,LeVine, Harry,Green, Keith D.,Tsodikov, Oleg V.,Garneau-Tsodikova, Sylvie
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supporting information
p. 9418 - 9426
(2015/09/15)
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- Novel acid-type cyclooxygenase-2 inhibitors: Design, synthesis, and structure-activity relationship for anti-inflammatory drug
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Cyclooxygenase (COX) is a key rate-limiting enzyme for prostaglandin (PG) production cascades in the human body. The mechanisms of both the anti-inflammation effects and the side-effects of traditional COX inhibitors are associated with the existence of two COX isoforms. Thus while COX-1 is predominantly expressed ubiquitously and constitutively, and it serves a housekeeping role in processes such as gastrointestinal (GI) mucosa protection, COX-2 is absent or exhibits a low level of expression in most tissues, and is highly upregulated in response to endotoxin, virus, inflammatory or tissue-injury stimuli/signals, and tumour promoter in the various types of organs, tissues, and cells. Furthermore, COX-2 contribution to PGE2 and PGI2 production evokes and sustains systemic or peripheral inflammatory disease, but it is not involved in the COX-1-mediated GI tract events. Also, hypersensitivity of aspirin owing to its inhibitory action against COX-1 is a significant concern clinically. Consequently, highly selective COX-2 inhibitors have been needed for the treatment of inflammatory- and inflammation related-diseases that include pyrexia, inflammation, pain, rheumatoid arthritis, osteoarthritis, and cancers. In this study, a series of novel [2-{[(4-substituted or 4,5-disubstituted)-pyridin-2-yl]carbonyl}-(5- or 6-substituted or 5,6-disubstituted)-1H-indol-3-yl]acetic acid analogues was designed, synthesized, and evaluated to identify potent and selective COX-2 inhibitors as potential agents against inflammatory diseases. As significant findings, the present study clarified unique structure-activity relationship of the analogues toward potent and selective COX-2 inhibition in vitro, and identified 2-{6-fluoro-2-[4-methyl-2-pridinyl)carbonyl]-1H-indol-3-yl}acetic acid as a potent and selective COX-2 inhibitor in vitro that demonstrated orally potent anti-inflammation efficacy against carrageenan-induced oedema formation in the foot of SPF/VAF male SD rats as a peripheral inflammation model in vivo.
- Hayashi, Shigeo,Ueno, Naomi,Murase, Akio,Nakagawa, Yoko,Takada, Junji
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experimental part
p. 179 - 195
(2012/07/27)
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- PYRAZOLE DERIVATIVE
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A compound represented by Formula (I): wherein Ar1 represents Formula (II): Ar2 represents a 5- or 6-membered aromatic heterocyclic group which may be substituted; and X represents Formula (III): a salt thereof, or a solvate of the compound or the salt. A potent platelet aggregation suppressant which does not inhibit COX-1 and COX-2 is provided.
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Page/Page column 58
(2010/11/27)
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- AMIDOPYRAZOLE DERIVATIVE
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A platelet coagulation inhibitor which inhibits neither COX-1 nor COX-2 is provided. The inhibitor is a compound represented by general formula (I): wherein Ar1 and Ar2 independently represent a 5- or 6-membered aromatic heterocyclic group optionally substituted with 1 to 3 substituents, or a phenyl group optionally substituted with 1 to 3 substituents; R1 represents a lower acyl group, carboxyl group, a lower alkoxycarbonyl group, a lower alkoxy group, a lower alkyl group optionally substituted with 1 or 2 substituents, a carbamoyl group optionally substituted with 1 or 2 substituents, an oxamoyl group optionally substituted with 1 or 2 substituents, an amino group optionally substituted with 1 or 2 substituents, a 4- to 7-membered alicyclic heterocyclic group optionally substituted with 1 or 2 substituents, a phenyl group optionally substituted with 1 to 3 substituents, or a 5- or 6-membered aromatic heterocyclic group optionally substituted with 1 to 3 substituents; and R2 represents hydrogen atom, a halogeno group, or the like.
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Page/Page column 34; 44
(2010/11/23)
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- Synthesis of DNA triangles with vertexes of Bis(terpyridine)iron(II) complexes
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The synthesis of the terpyridine derivative 1 tethered to a DNA oligonucleotide and its use for the preparation of two-way branched metal-organic modules capable of self-assembling into DNA triangles are described. Copyright
- Choi, Jin Seok,Kang, Chang Won,Jung, Kisung,Yang, Jung Woon,Kim, Yang-Gyun,Han, Hogyu
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p. 8606 - 8607
(2007/10/03)
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- Steric control of directional isomerism in dicopper(I) helicates of asymmetrically substituted 2,2':6',2':2,6'-quaterpyridine derivatives
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Derivatives of 2,2':6',2'':2'',6'''-quaterpyridine have been prepared which are asymmetrically substituted with alkyl groups in the 4- or 6- position and with various substituents in the 4'-position. These ligands form dicopper(I) double helicates which have been investigated by 1H and 13C NMR spectroscopic techniques. The formation of helical isomers is shown to depend on the intramolecular interactions between the constituent helicands of the double helicate; 4'-methyl substituents undergo steric interactions with the 4-substituent of the partner helicand, leading to a modest selectivity, although bulky 4-substituents decrease selectivity. In the absence of 4'-substituents, the smaller pitch permits steric interactions between like 4-substituents of the component helicands. In each case, formation of the head-to-head helicate isomer is preferred.
- Constable,Heirtzler,Neuburger,Zehnder
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p. 5606 - 5617
(2007/10/03)
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- Substituent Effects on Photochemical Hydrogen Abstraction in 2-Acylpyridines, 2-Acylpyrazines, and 4-Acylpyrimidines
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Stern-Volmer quenching of the photochemistry of 1c indicates that N- and O-abstraction (eqs 1 and 2, respectively) are quenched at different rates (Figure 1).For quenching of 2c kqτ is 157 M-1 and for 3c, 64 M-1.When 1c is sensitized with triplet sensitizers of increasing ET,N-abstraction increases (Table 1).These data indicate that N- and O-abstraction in 1c take place from distiguishable triplet states.Survey of Φp's of ring-substituted ketones 1b-d, 6d, 7a,b,d, 8b, 9b,d, 10b, and 11d demonstartes the effect of substitution on the competition between N- and O-abstraction (Table 2).For methyl- and dicyano-substituted ketones, the results can be understood simply in terms of shifts in ET of the n?* and ??* states of the heterocycle.The photochemistry of all these ketones requires consideration of interactions among three triplet states.
- Rao, C. Janakiram,Agosta, William C.
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p. 2125 - 2131
(2007/10/02)
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