- Synthesis and evaluation of new sesamol-based phenolic acid derivatives with hypolipidemic, antioxidant, and hepatoprotective effects
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The objective of this study is to synthesize a series of sesamol-based phenolic acid derivatives, which were designed by combination principle. The hypolipidemic activity of all these compounds was preliminarily screened by acute hyperlipidemic mice model induced by Triton WR 1339, in which compound T6 exhibited more significant reducing plasma TG and TC than fenofibrate. Compound T6 was also found to obviously decrease TG and TC both in the plasma and hepatic tissue of high-fat-diet-induced hyperlipidemic mice. Moreover, T6 showed hepatoprotective effects, which remarkable amelioration in characteristic liver enzymes was examined and the histopathological observation displayed that compound T6 inhibited lipids accumulation in the hepatic. The levels of PPAR-α receptor related to lipids metabolism in hepatic tissue were upregulated after T6 treatment. Other potent effects of T6 such as antioxidant and anti-inflammatory activity were also observed. On the bases of these findings, compound T6 may serve as an effective hypolipidemic and hepatoprotective agent. [Figure not available: see fulltext.]
- Xie, Yundong,Liu, Jiping,Shi, Yongheng,Bin Wang,Wang, Xiaoping,Wang, Wei,Sun, Meng,Xu, Xinya,He, Shipeng
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p. 1688 - 1702
(2021/07/26)
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- Catalytic δ-hydroxyalkynone rearrangement in the stereoselective total synthesis of centrolobine, engelheptanoxides A and C and analogues
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A catalytic stereoselective total synthesis of centrolobine and engelheptanoxides A and C has been completed via a metal-free catalytic δ-hydroxyalkynone rearrangement to 2,3-dihydro-4H-pyran-4-one and diastereoselective hydrogenation to the all syn-2,4,6-trisubstituted pyran strategy. The onliest required chirality was introduced by Jacobsen kinetic resolution, which further directed the diastereoselective hydrogenation. A first stereoselective synthesis of engelheptanoxide A is also accomplished. The analogues and derivatives of centrolobine and engelheptanoxides prepared were evaluated for antitubercular activity against M. tuberculosis H37Rv ATCC 27294.
- Ahmad, Mohammad N.,Chopra, Sidharth,Fernandes, Rodney A.,Kumar, Praveen
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- Photo-Promoted Decarboxylative Alkylation of α, β-Unsaturated Carboxylic Acids with ICH2CN for the Synthesis of β, γ-Unsaturated Nitriles
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An efficient, catalyst/photocatalyst-free, and cost-effective methodology for the decarboxylative alkylation of α,β-unsaturated carboxylic acids to synthesize β,γ-unsaturated nitriles has been developed. The reaction proceeded in an environmentally benign atmosphere of blue light-emitting diode irradiation with K2CO3 and water at room temperature. The methodology worked for a wide range of substrates (22 examples) with up to 83% yield. The protocol is also compatible for gram-scale synthesis.
- Pan, Chunxiang,Yang, Chunhui,Li, Kangkui,Zhang, Keyang,Zhu, Yuanbin,Wu, Shiyuan,Zhou, Yongyun,Fan, Baomin
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supporting information
p. 7188 - 7193
(2021/10/01)
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- Synthesis, biological evaluation and computational studies of acrylohydrazide derivatives as potential Staphylococcus aureus NorA efflux pump inhibitors
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The NorA efflux pump decreases the intracellular concentration of fluoroquinolones (ciprofloxacin, norfloxacin) by effluxing them from Staphylococcus aureus cells. The synthesis of novel acrylohydrazide derivatives was achieved using well-known reactions and were characterized by various spectroscopy techniques. The synthesized 50 compounds were evaluated for the NorA efflux pump inhibition activity against S. aureus SA-1199B (norA++) and K1758 (norA-) strains. The study provided two most active compounds viz. 19 and 52. Compound 19 was found to be most active in potentiating effect of norfloxacin and also it showed enhanced uptake, efflux inhibition in ethidium bromide assay. Further compound 19 also enhanced post antibiotic effect and reduced mutation prevention concentration of norfloxacin. The homology modeling study was performed to elucidate three-dimensional structure of NorA. Docking studies of potent molecules were done to find the binding affinity and interaction with active site residues. Further, all the tested compounds exhibited good ADME and drug-likeness properties in- silico. Based on the in-silico studies and detailed in vitro studies, acrylohydrazides derivatives may be considered as potential NorA EPI candidates.
- Kumar, Gautam,Goutami Godavari, Ambati,Tambat, Rushikesh,Kumar, Siva,Nandanwar, Hemraj,Elizabeth Sobhia,Jachak, Sanjay M.
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- Design, synthesis and evaluation of phenylfuroxan nitric oxide-donor phenols as potential anti-diabetic agents
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Both nitric oxide (NO) dysfunction and oxidative stress have been regarded as the important factors in the development and progression of diabetes and its complications. Multifunctional compounds with hypoglycemic, NO supplementation and anti-oxidation will be the promising agents for treatment of diabetes. In this study, six phenylfuroxan nitric oxide (NO) donor phenols were synthesized, which were designed via a combination approach with phenylfuroxan NO-donor and natural phenols. These novel synthetic compounds were screened in vitro for α-glucosidase inhibition, NO releasing, anti-oxidation, anti-glycation and anti-platelet aggregation activity as well as vasodilatation effects. The results exhibited that compound T5 displayed more excellent activity than other compounds. Moreover, T5 demonstrated significant hypoglycemic activity in diabetic mice and oral glucose tolerance test (OGTT) mice. T5 also showed NO releasing and anti-oxidation in diabetic mice. Based on these results, compound T5 deserves further study as potential new multifunctional anti-diabetic agent with antioxidant, NO releasing, anti-platelet aggregation and vasodilatation properties.
- Xie, Yun-Dong,Shao, Li-Hua,Wang, Qiu-Tang,Bai, Yue,Li, Na,Yang, Guangde,Li, Yi-Ping,Bian, Xiao-Li
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- Structural isomers of cinnamic hydroxamic acids block HCV replication via different mechanisms
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A set of ortho-, meta- and para-substituted cinnamic hydroxamic acids (CHAs) was synthesized. In each series of structural isomers, a phenyl substituent was linked to an aromatic ring of the parent cinnamic acid via a linker of one to four atoms in length
- Kozlov, Maxim V.,Konduktorov, Konstantin A.,Malikova, Alsu Z.,Kamarova, Kamila A.,Shcherbakova, Anastasia S.,Solyev, Pavel N.,Kochetkov, Sergey N.
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- Synthesis of cinnamic amide derivatives and their anti-melanogenic effect in α-MSH-stimulated B16F10 melanoma cells
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Of the three enzymes that regulate the biosynthesis of melanin, tyrosinase and its related proteins TYRP-1 and TYRP-2, tyrosinase is the most important because of its ability to limit the rate of melanin production in melanocytes. For treating skin pigmentation disorders caused by an excess of melanin, the inhibition of tyrosinase enzyme is by far the most established strategy. Cinnamic acid is a safe natural product with an (E)-β-phenyl-α,β-unsaturated carbonyl motif that we have previously shown to play an important role in high tyrosinase inhibition. Since cinnamic acid is relatively hydrophilic, which hinders its absorption on the skin, fifteen less hydrophilic cinnamic amide derivatives (1–15) were designed as safe and more potent tyrosinase inhibitors and were synthesized through a Horner-Wadsworth-Emmons reaction. The use of conc-HCl and acetic acid for debenzylation of the O-benzyl-protected cinnamic amides 40–54 produced the following three results. 1) Cinnamic amides 43, 48, and 53 with a 2,4-dibenzyloxyphenyl group, irrespective of the amine type of the amides, produced complex compounds with high polarity. 2) Cinnamic amides 40–42, 44, 50–52, and 54 with a benzylamino, or diethylamino group produced the desired debenzylated cinnamic amides 1–3, 5, 10–13, and 15. 3) Cinnamic amides 45–47, and 49 with an anilino moiety provided 3,4-dihydroquinolinones 16–19 through intramolecular Michael addition of the anilide group. Notably, the use of BBr3 as an alternative debenzylating agent for debenzylation of cinnamic amides 45–49 with the anilino moiety provided our desired cinnamic amides 6–10 without inducing the intramolecular Michael addition. Debenzylation of cinnamic amides 43, 48, and 53 with a 2,4-dibenzyloxyphenyl group was also successfully accomplished using BBr3 to give 4, 9, and 14. Among the nine compounds that inhibited mushroom tyrosinase more potently at 25 μM than kojic acid, four cinnamic amides 4, 5, 9, and 14 showed 3-fold greater tyrosinase inhibitory activity than kojic acid. The docking simulation using tyrosinase indicated that these four cinnamic amides (?6.2 to ?7.9 kcal/mol) bind to the active site of tyrosinase with stronger binding affinity than kojic acid (?5.7 kcal/mol). All four cinnamic amides inhibited melanogenesis and tyrosinase activity more potently than kojic acid in α-MSH-stimulated B16F10 melanoma cells in a dose-dependent manner without cytotoxicity. The strong correlation between tyrosinase activity and melanin content suggests that the anti-melanogenic effect of cinnamic amides is due to tyrosinase inhibitory activity. Considering that the cinnamic amides 4, 9, and 14, which exhibited strong inhibition on mushroom tyrosinase and potent anti-melanogenic effect in B16F10 cells, commonly have a 2,4-dihydroxyphenyl substituent, the 2,4-dihydroxyphenyl substituent appears to be essential for high anti-melanogenesis. These results support the potential of these four cinnamic amides as novel and potent tyrosinase inhibitors for use as therapeutic agents with safe skin-lightening efficiency.
- Ullah, Sultan,Kang, Dongwan,Lee, Sanggwon,Ikram, Muhammad,Park, Chaeun,Park, Yujin,Yoon, Sik,Chun, Pusoon,Moon, Hyung Ryong
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- Tyrosinase inhibition and anti-melanin generation effect of cinnamamide analogues
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Abnormal melanogenesis results in excessive production of melanin, leading to pigmentation disorders. As a key and rate-limiting enzyme for melanogenesis, tyrosinase has been considered an important target for developing therapeutic agents of pigment disorders. Despite having an (E)-β-phenyl-α,β-unsaturated carbonyl scaffold, which plays an important role in the potent inhibition of tyrosinase activity, cinnamic acids have not attracted attention as potential tyrosinase inhibitors, due to their low tyrosinase inhibitory activity and relatively high hydrophilicity. Given that cinnamic acids’ structure intrinsically features this (E)-scaffold and following our experience that minute changes in the chemical structure can powerfully affect tyrosinase activity, twenty less hydrophilic cinnamamide derivatives were designed as potential tyrosinase inhibitors and synthesised using a Horner-Wadsworth-Emmons reaction. Four of these cinnmamides (4, 9, 14, and 19) exhibited much stronger mushroom tyrosinase inhibition (over 90% inhibition) at 25 μM compared to kojic acid (20.57% inhibition); crucially, all four have a 2,4-dihydroxy group on the β-phenyl ring of the scaffold. A docking simulation using tyrosinase indicated that the four cinnamamides exceeded the binding affinity of kojic acid, and bound more strongly to the active site of tyrosinase. Based on the strength of their tyrosinase inhibition, these four cinnamamides were further evaluated in B16F10 melanoma cells. All four cinnamamides, without cytotoxicity, exhibited higher tyrosinase inhibitory activity (67.33 – 79.67% inhibition) at 25 μM than kojic acid (38.11% inhibition), with the following increasing inhibitory order: morpholino (9) = cyclopentylamino (14) cyclohexylamino (19) N-methylpiperazino (4) cinnamamides. Analysis of tyrosinase activity and melanin content in B16F10 cells showed that the four cinnamamides dose-dependently inhibited both cellular tyrosinase activity and melanin content and that their inhibitory activity at 25 μM was much better than that of kojic acid. The results of melanin content analysis well matched those of the cellular tyrosinase activity analysis, indicating that tyrosinase inhibition by the four cinnamamides is a major factor in the reduction of melanin production. These results imply that these four cinnamamides with a 2,4-dihydroxyphenyl group can act as excellent anti-melanogenic agents in the treatment of pigmentation disorders.
- Ullah, Sultan,Park, Chaeun,Ikram, Muhammad,Kang, Dongwan,Lee, Sanggwon,Yang, Jungho,Park, Yujin,Yoon, Sik,Chun, Pusoon,Moon, Hyung Ryong
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- Novel cinnamic acid–tryptamine hybrids as potent butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study
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A novel series of cinnamic acid–tryptamine hybrids was designed, synthesized, and evaluated as cholinesterase inhibitors. Anticholinesterase assays showed that all of the synthesized compounds displayed a clearly selective inhibition of butyrylcholinesterase (BChE), but only a moderate inhibitory effect toward acetylcholinesterase (AChE) was detected. Among these cinnamic acid–tryptamine hybrids, compound 7d was found to be the most potent inhibitor of BChE with an IC50 value of 0.55 ± 0.04 μM. This compound showed a 14-fold higher inhibitory potency than the standard drug donepezil (IC50 = 7.79 ± 0.81 μM) and inhibited BChE through a mixed-type inhibition mode. Moreover, a docking study revealed that compound 7d binds to both the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of BChE. Also, compound 7d was evaluated against β-secretase, which exhibited low activity (inhibition percentage: 38%).
- Ghafary, Shahrzad,Najafi, Zahra,Mohammadi-Khanaposhtani, Maryam,Nadri, Hamid,Edraki, Najmeh,Ayashi, Neda,Larijani, Bagher,Amini, Mohsen,Mahdavi, Mohammad
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- Synthesis, Crystallization Studies, and in vitro Characterization of Cinnamic Acid Derivatives as SmHDAC8 Inhibitors for the Treatment of Schistosomiasis
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Schistosomiasis is a neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy relies on mass treatment with only one drug: praziquantel. Based on the 3-chlorobenzothiophene-2-hydroxamic acid J1075, a series of hydroxamic acids with different scaffolds were prepared as potential inhibitors of Schistosoma mansoni histone deacetylase 8 (SmHDAC8). The crystal structures of SmHDAC8 with four inhibitors provided insight into the binding mode and orientation of molecules in the binding pocket as well as the orientation of its flexible amino acid residues. The compounds were evaluated in screens for inhibitory activity against schistosome and human HDACs. The most promising compounds were further investigated for their activity toward the major human HDAC isotypes. The most potent inhibitors were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Two of the compounds showed significant, dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture.
- Bayer, Theresa,Chakrabarti, Alokta,Lancelot, Julien,Shaik, Tajith B.,Hausmann, Kristin,Melesina, Jelena,Schmidtkunz, Karin,Marek, Martin,Erdmann, Frank,Schmidt, Matthias,Robaa, Dina,Romier, Christophe,Pierce, Raymond J.,Jung, Manfred,Sippl, Wolfgang
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p. 1517 - 1529
(2018/08/01)
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- Design, synthesis and anti-melanogenic effect of cinnamamide derivatives
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Pigmentation disorders are attributed to excessive melanin which can be produced by tyrosinase. Therefore, tyrosinase is supposed to be a vital target for the treatment of disorders associated with overpigmentation. Based on our previous findings that an (E)-β-phenyl-α,β-unsaturated carbonyl scaffold can play a key role in the inhibition of tyrosinase activity, and the fact that cinnamic acid is a safe natural substance with a scaffolded structure, it was speculated that appropriate cinnamic acid derivatives may exhibit potent tyrosinase inhibitory activity. Thus, ten cinnamamides were designed, and synthesized by using a Horner-Emmons olefination as the key step. Cinnamamides 4 (93.72% inhibition), 9 (78.97% inhibition), and 10 (59.09% inhibition) with either a 2,4-dihydroxyphenyl, or 4-hydroxy-3-methoxyphenyl substituent showed much higher mushroom tyrosinase inhibition at 25 μM than kojic acid (18.81% inhibition), used as a positive control. Especially, the two cinnamamides 4 and 9 having a 2,4-dihydroxyphenyl group showed the strongest inhibition. Docking simulation with tyrosinase revealed that these three cinnamamides, 4, 9, and 10, bind to the active site of tyrosinase more strongly than kojic acid. Cell-based experiments carried out using B16F10 murine skin melanoma cells demonstrated that all three cinnamamides effectively inhibited cellular tyrosinase activity and melanin production in the cells without cytotoxicity. There was a close correlation between cellular tyrosinase activity and melanin content, indicating that the inhibitory effect of the three cinnamamides on melanin production is mainly attributed to their capability for cellular tyrosinase inhibition. These results imply that cinnamamides having the (E)-β-phenyl-α,β-unsaturated carbonyl scaffolds are promising candidates for skin-lighting agents.
- Ullah, Sultan,Park, Yujin,Ikram, Muhammad,Lee, Sanggwon,Park, Chaeun,Kang, Dongwan,Yang, Jungho,Akter, Jinia,Yoon, Sik,Chun, Pusoon,Moon, Hyung Ryong
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p. 5672 - 5681
(2018/10/24)
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- Polystyrene supported palladium nanoparticles catalyzed cinnamic acid synthesis using maleic anhydride as a substitute for acrylic acid
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Maleic anhydride was explored as a substitute for acrylic acid to synthesize cinnamic acids from aryl halides under heterogeneous palladium catalyzed conditions. The combined role of surface and impregnated catalyst together performed an upright engineering to hold in situ generated molecules on the surface and subsequently facilitate their interaction for the desired product synthesis. Overall, a surface mediated approach for cinnamic acid synthesis from maleic anhydride following a major unexplored pathway through catalyst promoted decarboxylation was critically investigated.
- Thakur, Vandna,Kumar, Sandeep,Das, Pralay
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p. 3692 - 3697
(2017/09/07)
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- Phenylsulfonylfuroxan NO-donor phenols: Synthesis and multifunctional activities evaluation
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Phenylsulfonyfuroxan nitric oxide (NO)-donor phenols were designed, synthesized and evaluated. The compounds were designed through a symbiotic approach using selected phenols and phenylsulfonylfuroxan NO-donor. The antioxidant activities of the hybrid compounds T2–T6 showed to be good in vivo. Compounds T4 and T6 revealed excellent yeast α-glucosidase inhibitory activity and anti-glycosylation activity. All of the compounds exhibited strong NO releasing activity and significant anti-platelet aggregation activity. The inhibition of platelet aggregation was more than 50% at low concentration (1.5?μM) and 95% at higher concentration (15?μM and 150?μM). The vasodilatation experiment demonstrated that the six compounds under test exhibited definite vasodilation activity (pIC50 ranged from 5.698 to 6.383), especially compound T6 (pIC50 was 6.383) which was similar to sodium nitroprusside (pIC50 was 6.786). Both anticoagulant and vasodilatation effects were correlated with their NO releasing activities. These hybrid phenylsulfonyfuroxan-based NO-donor phenols offer a multifunctional prodrug design concept for the development of therapeutic or preventive agents for metabolic syndrome.
- Xie, Yundong,Yang, Yaping,Li, Sen,Xu, Yanhong,Lu, Wenfang,Chen, Zizhang,Yang, Guangde,Li, Yiping,Cao, Yongxiao,Bian, Xiaoli
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p. 4407 - 4413
(2017/07/22)
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- Design, synthesis,: In vitro and in vivo evaluation of tacrine-cinnamic acid hybrids as multi-target acetyl- and butyrylcholinesterase inhibitors against Alzheimer's disease
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Previously, we have reported tacrine-ferulic acid hybrids as multi-target cholinesterase inhibitors against Alzheimer's disease. However, the detailed structure-activity relationship (SAR), especially regarding the ferulic acid moiety, has yet to be eluci
- Chen, Yao,Lin, Hongzhi,Zhu, Jie,Gu, Kai,Li, Qi,He, Siyu,Lu, Xin,Tan, Renxiang,Pei, Yuqiong,Wu, Liang,Bian, Yaoyao,Sun, Haopeng
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p. 33851 - 33867
(2017/07/17)
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- Concise access toward chiral hydroxy phenylpropanoids: formal synthesis of virolongin B; kigelin; kurasoin A; 4-hydroxysattabacin, and actinopolymorphol A
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A simple, two step strategy consisting of Sharpless asymmetric dihydroxylation followed by regioselective breaking of [Formula presented] bond is utilized to target key chiral intermediates of natural products virolongin B, kigelin, kurasoin A, 4-hydroxy-sattabacin, and actinopolymorphol A. Derivatives of enantiopure hydroxy phenyl propanoids and α-hydroxy Weinreb amides are synthesized. The reductive cleavage of [Formula presented] bond in a regioselective manner is obtained using Pd/C in methanol.
- Patil, Sagar N.,Tilve, Santosh G.
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supporting information
p. 3371 - 3375
(2016/07/11)
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- Polymerizable chiral compd.
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The invention provides a polymerizable chiral compound which has strong HTP and is excellent in solubility. The polymerizable chiral compound shown in a general form (I) has strong HTP and a low melting point. As the melting point is low, the polymerizable chiral compound has excellent solubility with other liquid crystal compounds and is useful to be a composition material of polymerizable liquid crystal composition. In addition, as the polymerizable chiral compound has a strong torque force, the polymerizable chiral compound can be used to manufacture optical anisotropy of excellent optical properties. The optical anisotropy can be used in deflection plates, phase difference plates, selective reflection plates, etc.
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Paragraph 0112
(2016/10/20)
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- ACRYLATE COMPOUND HAVING PHOTOREACTIVE GROUP, PHOTOREACTIVE ACRYLATE POLYMER AND PHOTO-ALIGNMENT LAYER COMPRISING THE SAME
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The present invention relates to an acrylate compound which has excellent orientation and orientation speed, properties that an orientation direction easily changes toward a polarizing direction, excellent solubility in an organic solvent, and processability; to a photoreactive acrylate polymer and to a photo-alignment layer comprising the same.
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Paragraph 0140; 0141
(2016/10/09)
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- Vitamin D3 analogues that contain modified A- and seco-B-rings as hedgehog pathway inhibitors
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The hedgehog (Hh) signaling pathway is a developmental signaling pathway that has been implicated as a target for anti-cancer drug development in a variety of human malignancies. Several natural and synthetic vitamin D-based seco-steroids have been identified as potent inhibitors of Hh signaling with chemotherapeutic potential. These include the previously characterized analogue 4, which contains the northern CD-ring/side chain region of vitamin D3 (VD3) linked to an aromatic A-ring mimic through an ester bond. To further explore structure-activity relationships for this class of VD3-based Hh pathway inhibitors, we have designed, synthesized and evaluated several series of compounds that modify the length, composition, and stereochemical orientation of the ester linker. These studies have identified compounds 54 and 55, which contain an amine linker and an aromatic A-ring incorporating a para-phenol, as new lead compounds with enhanced potency against the Hh pathway (IC50 values Combining double low line 0.40 and 0.32 μM, respectively).
- Deberardinis, Albert M.,Raccuia, Daniel S.,Thompson, Evrett N.,Maschinot, Chad A.,Hadden, M. Kyle
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p. 156 - 171
(2015/02/19)
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- CYCLIC OLEFIN COMPOUND, PHOTOREACTIVE POLYMER AND ALIGNMENT LAYER COMPRISING THE SAME
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The present invention relates to: a cyclic olefin compound which exhibits excellent liquid crystal alignment properties and alignment speed, has a characteristic that the alignment direction can easily be varied depending on the polarization direction, an
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Paragraph 0227; 0228
(2016/12/12)
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- Synthesis, cytotoxicity and molecular modelling studies of new phenylcinnamide derivatives as potent inhibitors of cholinesterases
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The present study reports the synthesis of cinnamide derivatives and their biological activity as inhibitors of both cholinesterases and anticancer agents. Controlled inhibition of brain acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) may slow neurodegeneration in Alzheimer's diseases (AD). The anticholinesterase activity of phenylcinnamide derivatives was determined against Electric Eel acetylcholinesterase (EeAChE) and horse serum butyrylcholinesterase (hBChE) and some of the compounds appeared as moderately potent inhibitors of EeAChE and hBChE. The compound 3-(2-(Benzyloxy)phenyl)-N- (3,4,5-trimethoxyphenyl)acrylamide (3i) showed maximum activity against EeAChE with an IC50 0.29 ± 0.21 μM whereas 3-(2-chloro-6- nitrophenyl)-N-(3,4,5-trimethoxyphenyl)acrylamide (3k) was proved to be the most potent inhibitor of hBChE having IC50 1.18 ± 1.31 μM. To better understand the enzyme-inhibitor interaction of the most active compounds toward cholinesterases, molecular modelling studies were carried out on high-resolution crystallographic structures. The anticancer effects of synthesized compounds were also evaluated against cancer cell line (lung carcinoma). The compounds may be useful leads for the design of a new class of anticancer drugs for the treatment of cancer and cholinesterase inhibitors for Alzheimer's disease (AD).
- Saeed, Aamer,Mahesar, Parvez Ali,Zaib, Sumera,Khan, Muhammad Siraj,Matin, Abdul,Shahid, Mohammad,Iqbal, Jamshed
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- Synthesis of perspicamide A and related diverse analogues: Their bioevaluation as potent antileishmanial agents
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The first protocol for the synthesis of perspicamide A and related diverse analogues has been developed from economical and readily available starting materials. Furthermore, a few synthesized analogues, 24a, 24b, 24c, 24d, and 24l, exhibited potent activ
- Pandey, Anand Kumar,Sharma, Rashmi,Shivahare, Rahul,Arora, Ashish,Rastogi, Neeraj,Gupta, Suman,Chauhan, Prem M. S.
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p. 1534 - 1546
(2013/04/10)
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- Synthesis of substituted nitroolefins: A copper catalyzed nitrodecarboxylation of unsaturated carboxylic acids
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A novel, mild and convenient method for the nitrodecarboxylation of substituted cinnamic acid derivatives to their nitroolefins is achieved using a catalytic amount of CuCl (10 mol%) and tert-butyl nitrite (2 equiv.) as a nitrating agent in the presence of air. This reaction provides a useful method for the synthesis of β,β-disubstituted nitroolefin derivatives, which are generally difficult to access from other conventional methods. Additionally, this reaction is selective as the E-isomer of the acid derivatives furnishes the corresponding E-nitroolefins. One more salient feature of the method is, unlike other methods, no metal nitrates or HNO3 are employed for the transformation.
- Rokade, Balaji V.,Prabhu, Kandikere Ramaiah
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supporting information
p. 6713 - 6716
(2013/10/01)
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- Synthesis of derivatives of methyl rosmarinate and their inhibitory activities against matrix metalloproteinase-1 (MMP-1)
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A series of MMP-1 inhibitors have been identified based upon a methyl rosmarinate scaffold using structure-based drug design methods. The best compound in the series showed an IC50 value of 0.4 μM. A docking study was conducted for compound (S)
- Yuan, Hu,Lu, Weiqiang,Wang, Liyan,Shan, Lei,Li, Honglin,Huang, Jin,Sun, Qingyan,Zhang, Weidong
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supporting information
p. 148 - 157
(2013/05/09)
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- Total synthesis of (±)-decinine via an oxidative biaryl coupling with defined axial chirality
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The total synthesis of (±)-decinine has been achieved. The key steps in the synthesis involved the formation of lasubine II via a gold catalyzed annulation of 1-(but-3-yn-1-yl)piperidine and the formation of the 12-membered ring of decinine (1) with complementary atropselectivity via a VOF 3-mediated oxidative biaryl coupling reaction.
- Shan, Zhen-Hua,Liu, Ji,Xu, Ling-Min,Tang, Ye-Feng,Chen, Jia-Hua,Yang, Zhen
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supporting information; experimental part
p. 3712 - 3715
(2012/09/21)
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- CYCLIC OLEFIN COMPOUND, PHOTOREACTIVE POLYMER AND ALIGNMENT LAYER COMPRISING THE SAME
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Disclosed therein are a cyclic olefin compound, a photoreactive polymer, and an alignment layer comprising the photoreactive polymer, where the cyclic olefin compound can be used to provide the photoreactive polymer having not only excellences in liquid c
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Page/Page column 33
(2012/04/17)
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- Synthesis, molecular modeling and biological evaluation of β-ketoacyl-acyl carrier protein synthase III (FabH) as novel antibacterial agents
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A series of novel cinnamic acid secnidazole ester derivatives have been designed and synthesized, and their biological activities were also evaluated as potential inhibitors of FabH. These compounds were assayed for antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus. Compounds with potent antibacterial activities were tested for their E. coli FabH inhibitory activity. Compound 3n showed the most potent antibacterial activity with MIC of 1.56-6.25 μg/mL against the tested bacterial strains and exhibited the most potent E. coli FabH inhibitory activity with IC50 of 2.5 μM. Docking simulation was performed to position compound 3n into the E. coli FabH active site to determine the probable binding conformation.
- Zhang, Hong-Jia,Zhu, Di-Di,Li, Zi-Lin,Sun, Juan,Zhu, Hai-Liang
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experimental part
p. 4513 - 4519
(2011/09/12)
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- Synthesis, molecular modeling, and biological evaluation of cinnamic acid metronidazole ester derivatives as novel anticancer agents
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A series of novel cinnamic acid metronidazole ester derivatives have been designed and synthesized, and their biological activities were also evaluated as potential EGFR and HER-2 kinase inhibitors. Compound 3h showed the most potent biological activity (IC50 = 0.62 μM for EGFR and IC50 = 2.15 μM for HER-2). Docking simulation was performed to position compound 3h into the EGFR active site to determine the probable binding model. Antiproliferative assay results demonstrated that some of these compounds possessed good antiproliferative activity against MCF-7. Compound 3h with potent inhibitory activity in tumor growth inhibition may be a potential anticancer agent.
- Qian, Yong,Zhang, Hong-Jia,Zhang, Hao,Xu, Chen,Zhao, Jing,Zhu, Hai-Liang
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experimental part
p. 4991 - 4996
(2010/09/05)
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- Design and synthesis of novel 2-phenylaminopyrimidine (PAP) derivatives and their antiproliferative effects in human chronic myeloid leukemia cells
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A series of novel 2-phenylaminopyrimidine (PAP) derivatives structurally related to STI-571 were designed and synthesized. The abilities of these compounds to inhibit proliferation were tested in human chronic myeloid leukemia K562 cells. (E)-3-(2-bromophenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2- ylamino)phenyl]acrylamide( 12d) was the most effective cell growth inhibitor and was 3-fold more potent than STI-571.
- Chang, Sheng,Yin, Shi-Liang,Wang, Jian,Jing, Yong-Kui,Dong, Jin-Hua
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experimental part
p. 4166 - 4179
(2009/12/28)
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- N-(3-(4-Hydroxyphenyl)-propenoyl)-amino acid tryptamides as SIRT2 inhibitors
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A series of N-(3-(4-hydroxyphenyl)-propenoyl)-amino acid tryptamides was based on a previously reported new SIRT2 inhibitor from our group, and it was designed to study if the molecular size of the compound could be reduced. The most potent compounds, N-(3-(4-hydroxyphenyl)-propenoyl)-2-aminoisobutyric acid tryptamide and N-(3-(4-hydroxyphenyl)-propenoyl)-l-alanine tryptamide, were equipotent, 30% smaller in molecular weight, and slightly more selective (SIRT2/SIRT1) than the parent compound.
- Kiviranta, Paeivi H.,Leppaenen, Jukka,Rinne, Valtteri M.,Suuronen, Tiina,Kyrylenko, Olga,Kyrylenko, Sergiy,Kuusisto, Erkki,Tervo, Anu J.,Jaervinen, Tomi,Salminen, Antero,Poso, Antti,Wallen, Erik A.A.
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p. 2448 - 2451
(2008/02/03)
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- Antioxidant and antimicrobial activity evaluation of polyhydroxycinnamic acid ester derivatives
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Polyhydroxycinnamic acid esters 5a-p have been synthesized starting from the appropriately substituted benzaldehydes. The antioxidant activity of these esters has been determined by superoxide free radical scavenging activity and DPPH free radical scavenging activity. The SAR studies reveal that pyrogallol, catechol moieties are essential for good antioxidant activity and an increase in the length of alkyl chain of the ester decreases the activity. Butyl hydroxycinnamates exhibit higher antibacterial activity among the synthesized hydroxycinnamates 5a-p, but, none of these show significant antifungal activity.
- Venkateswarlu, Somepalli,Ramachandra, Mareullapudi S.,Krishnaraju, Alluri V.,Trimurtulu, Golakoti,Subbaraju, Gottumukkala V.
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p. 252 - 257
(2007/10/03)
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- Very short and efficient syntheses of the spermine alkaloid kukoamine A and analogs using isolable succinimidyl cinnamates
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Direct selective acylation of the primary amino functions of spermine and spermidine with a variety of isolable succinimidyl cinnamates, followed by catalytic hydrogenation, gave high yields of the spermine alkaloid kukoamine A and analogs suitable for structure-activity relationship studies. Suitable succinimidyl cinnamates were readily obtained through Wittig reaction of aromatic aldehydes with the ylides Ph3P=CRCO2Me, followed by saponification and activation with N-hydroxysuccinimide in the presence of N,N'-dicyclohexylcarbodiimide. Copyright
- Garnelis, Thomas,Athanassopoulos, Constantinos M.,Papaioannou, Dionissios,Eggleston, Ian M.,Fairlamb, Alan H.
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p. 264 - 265
(2007/10/03)
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- Competitive formation of β-amino acids, propenoic, and ylidenemalonic acids by the Rodionov reaction from malonic acid, aldehydes, and ammonium acetate in alcoholic medium
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The Rodionov reaction of 49 available aliphatic and aromatic aldehydes with malonic acid and ammonium acetate in alcoholic medium, resulting in formation of β-amino acids, propenoic, and ylidenemalonic acids, was studied. Certain regioselectivity regularities of the reaction were revealed. Among the variety of ketones studied, cyclohexanone is the only whose reaction yields a β-amino acid. Unusual dehydrofluorination of 6-chloro-2-fluorocinnamic acid under the Rodionov reaction was discovered. 2005 Pleiades Publishing, Inc.
- Lebedev,Lebedeva,Sheludyakov,Kovaleva,Ustinova,Kozhevnikov
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p. 1113 - 1124
(2007/10/03)
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- Substituted β-alanine derivatives as cell adhesion inhibitors
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β-Alanine derivatives of Formula I are antagonists of VLA-4 and/or α4β7, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of asthma, allergies, inflammation, multiple sclerosis, and other inflammatory and autoimmune disorders.
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- CARBOXAMIDES DERIVATIVES
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The present invention relates to carboxamides which are useful as an active ingredient of pharmaceutical preparations. The carboxamides of the present invention have IP receptor antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with IP receptor antagonistic activity.Such diseases include urological diseases or disorder as follows: bladder outlet obstruction, overactive bladder, urinary incontinence, detrusor hyper-reflexia, detrusor instability, reduced bladder capacity, frequency of micturition, urge incontinence, stress incontinence, bladder hyperreactivity, benighn prostatic hypertrophy (BPH), prostatitis, urinary frequency, nocturia, urinary urgency, pelvic hypersensitivity, urethritis, pelvic pain syndrome, prostatodynia, cystitis, or idiophatic bladder hypersensitivity.The compounds of the present invention are also useful for treatment of pain including, but not limited to inflammatory pain, neuropathic pain, acute pain, chronic pain, dental pain, premenstrual pain, visceral pain, headaches, and the like; hypotension;hemophilia and hemorrhage; and inflammation, since the diseases are alleviated by treatment with an IP receptor antagonist.
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- A 13C NMR study of the structure of four cinnamic acids and their methyl esters
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The 13C NMR spectra, both in DMSO solution and in the solid state of four cinnamic acids (p-methoxy, p-hydroxy, p-methyl, p-chloro) and their corresponding methyl esters have been recorded. The two main results in the solid state are: (i) the only significant difference between acids and esters chemical shifts concerns the C=O group which, on average, appears at 173 ppm in the acids and 168 ppm in the esters; (ii) the signals of the ortho and meta carbons both in the acids and the esters are splitted. The two "anomalies" dissapear in DMSO solution. These observations can be rationalized using simple GIAO/B3LYP/6-31G* calculations.
- Silva, A. M. S.,Alkorta, I.,Elguero, J.,Silva, V. L. M.
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- Constrained amino acids. An approach to the synthesis of 3-substituted prolines
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The synthesis of diastereomeric substituted proline peptidomimetics as conformationally restricted tyrosine derivatives 1a,b has been accomplished utilizing the intramolecular hydroboration-cycloalkylation of azido-olefins 7a,b as the key step.
- Waid, Philip P.,Flynn, Gary A.,Huber, Edward W.,Sabol, Jeffrey S.
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p. 4091 - 4094
(2007/10/03)
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- Gem-dichlorocyclopropanes as antitumor agents
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Gem-Dichlorocyclopropanes (Analog II derivatives) which demonstrate antiproliferative activity toward MCF-7 cells, in vitro and are generally not reversed by estradiol or having intrinsic estrogenicity (except the hydroxyphenyl derivative Compound 30). In general the cyclopropane compounds have the formula: STR1 or any pharmaceutically acceptable salt thereof. X is selected from a group consisting of hydrogen and halogen atoms. The group R1 may be a hydrogen atom, an alkyl group, an acyl group, or an arylalkyl group. The group R2 may be a hydrogen atom, an unsubstituted aryl group or a substituted aryl group. The group R3 may be a hydrogen atom, an alkyl group, a cycloalkyl group, a substituted aryl group or an unsubstituted aryl group. The group R4 may be a hydrogen atom, an unsubstituted aryl group or a substituted aryl group. The R4 is absent when R3 is a cycloalkyl group having a first position carbon and a terminal position carbon bonded to the same carbon of the cyclopropane. Further, no more than any two of R2, R3 and R4 has an aryl group.
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- A Study on Horseradish Peroxidase-mediated Coupling of Phenolesters, Directed to Synthesis of Lythraceae Alkaloids
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Phenolesters 2, 6 and 13 were used as substrates for the oxidative coupling by means of horseradish peroxidase/hydrogen peroxide system (HRPO/H2O2).The results are discussed from the viewpoint of the possible applications of phenolesters as model compounds for the synthesis of Lythraceae alkaloids.
- Krawczyk, Andrzej R.,Lipkowska, Ewa,Wrobel, Jerzy T.
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p. 115 - 122
(2007/10/02)
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