- Cinnamaldehydes inhibit cyclin dependent kinase 4/cyclin D1
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A series of cinnamaldehydes was synthesized for the study of inhibitory activity against cyclin dependent kinases (CDKs). A couple of compounds selectively inhibited cyclin D1-CDK4 with an IC50 value of 7-18 μM. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Jeong, Ha-Won,Kim, Mi-Ran,Son, Kwang-Hee,Young Han, Mi,Ha, Ji-Hong,Garnier, Matthieu,Meijer, Laurent,Kwon, Byoung-Mog
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- Enantiodivergent One-Pot Synthesis of Axially Chiral Biaryls Using Organocatalyst-Mediated Enantioselective Domino Reaction and Central-to-Axial Chirality Conversion
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Enantiodivergent one-pot synthesis of biaryls was developed using a catalytic amount of a single chiral source. A domino organocatalyst-mediated enantioselective Michael reaction and aldol condensation provided centrally chiral dihydronaphthalenes with excellent enantioselectivity, from which an enantiodivergent chirality conversion from central-to-axial chirality was achieved. Both enantiomers of biaryls were obtained with excellent enantioselectivity. All transformations can be conducted in a single reaction vessel. A plausible reaction mechanism for the enantiodivergence is proposed.
- Hayashi, Yujiro,Koshino, Seitaro,Kwon, Eunsang,Monde, Kenji,Taniguchi, Tohru
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p. 15786 - 15794
(2021/10/14)
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- Selective Synthesis of Z-Cinnamyl Ethers and Cinnamyl Alcohols through Visible Light-Promoted Photocatalytic E to Z Isomerization
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A photocatalytic E to Z isomerization of alkenes using an iridium photosensitizer under mild reaction conditions is disclosed. This method provides scalable and efficient access to Z-cinnamyl ether and allylic alcohol derivatives in high yields with excellent stereoselectivity. Importantly, this method also provides a powerful strategy for the selective synthesis of Z-magnolol and honokiol derivatives possessing potential biological activity.
- Li, Hengchao,Chen, Hang,Zhou, Yang,Huang, Jin,Yi, Jundan,Zhao, Hongcai,Wang, Wei,Jing, Linhai
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supporting information
p. 555 - 559
(2020/02/05)
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- Boron-catalyzed CC functionalization of allyl alcohols
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Tris(pentafluorophenyl)borane-catalyzed CC bond functionalization of arylallyl alcohols using donor-acceptor carbenes is presented. The allylic hydroxyl group is found to assist the product formation by neighboring group participation providing a clue towards mechanistic understanding. This method can also be employed to effect homologation of allyl alcohols to homoallyl alcohols. Overall, this metal-free transformation presents a novel disconnection strategy towards carbon-carbon bond scission and formation.
- Rao, Santhosh,Kapanaiah, Raja,Prabhu, Kandikere Ramaiah
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supporting information
p. 1301 - 1306
(2019/10/28)
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- Discovery of novel piperonyl derivatives as diapophytoene desaturase inhibitors for the treatment of methicillin-, vancomycin- and linezolid-resistant Staphylococcus aureus infections
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Inhibition of S. aureus diapophytoene desaturase (CrtN) could serve as an alternative approach for addressing the tricky antibiotic resistance by blocking the biosynthesis of carotenoid pigment which shields the bacterium from host oxidant killing. In this study, we designed and synthesized 44 derivatives with piperonyl scaffold targeting CrtN and the structure-activity relationships (SARs) were examined extensively to bring out the discovery of 21b with potent efficacy and better hERG safety profile compared to the first class CrtN inhibitor benzocycloalkane derivative 2. Except the excellent pigment inhibitory activity against wild-type S. aureus, 21b also showed excellent pigment inhibition against four pigmented MRSA strains. In addition, H2O2 killing and human whole blood killing assays proved 21b could sensitize S. aureus to be killed under oxidative stress conditions. Notably, the murine study in vivo validated the efficacy of 21b against pigmented S. aureus Newman, vancomycin-intermediate S. aureus Mu50 and linezolid-resistant S. aureus NRS271.
- Wei, Hanwen,Mao, Fei,Ni, Shuaishuai,Chen, Feifei,Li, Baoli,Qiu, Xiaoxia,Hu, Linghao,Wang, Manjiong,Zheng, Xinyu,Zhu, Jin,Lan, Lefu,Li, Jian
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p. 235 - 251
(2018/01/17)
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- Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity
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CrtN has been identified as an attractive and druggable target for treating pigmented Staphylococcus aureus infections. More than 100 new compounds were synthesized, which target the overwhelming the defects of the CrtN inhibitor 1. Analogues 23a and 23b demonstrated a significant activity against pigmented S. aureus Newman and 13 MRSA strains (IC50 = 0.02-10.5 nM), along with lower hERG inhibition (IC50 > 30 μM, ~10-fold decrease in comparison with 1). Furthermore, 23a and 23b were confirmed to reduce the staphylococcal load in the kidney and heart in a mouse model with normal treatment deeper than pretreatment ones, comparable even with vancomycin and linezolid. Remarkably, 23a could strongly block the pigment biosynthesis of these nine multidrug-resistant MRSA strains, including excellent activity against LRSA strains and VISA strains in vivo, and all of which demonstrated that 23a has a huge potential against intractable MRSA, VISA, and LRSA issues as a therapeutic drug.
- Li, Baoli,Ni, Shuaishuai,Mao, Fei,Chen, Feifei,Liu, Yifu,Wei, Hanwen,Chen, Wenhua,Zhu, Jin,Lan, Lefu,Li, Jian
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p. 224 - 250
(2018/02/10)
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- Novel Staphyloxanthin Inhibitors with Improved Potency against Multidrug Resistant Staphylococcus aureus
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Diapophytoene desaturase (CrtN) is a potential novel target for intervening in the biosynthesis of the virulence factor staphyloxanthin. In this study, 38 1,4-benzodioxan-derived CrtN inhibitors were designed and synthesized to overwhelm the defects of leading compound 4a. Derivative 47 displayed superior pigment inhibitory activity, better hERG inhibitory properties and water solubility, and significantly sensitized MRSA strains to immune clearance in vitro. Notably, 47 displayed excellent efficacy against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate MRSA, VISA), and NRS271 (linezolid-resistant MRSA, LRSA) comparable to that of linezolid and vancomycin in vivo.
- Ni, Shuaishuai,Li, Baoli,Chen, Feifei,Wei, Hanwen,Mao, Fei,Liu, Yifu,Xu, Yixiang,Qiu, Xiaoxi,Li, Xiaokang,Liu, Wenwen,Hu, Linghao,Ling, Dazheng,Wang, Manjiong,Zheng, Xinyu,Zhu, Jin,Lan, Lefu,Li, Jian
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supporting information
p. 233 - 237
(2018/03/21)
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- Copper-catalyzed [1,2]-rearrangements of allylic iodides and aryl α-diazoacetates
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The [1,2]- and [2,3]-rearrangements of iodonium ylides are synthetically useful reactions for the generation of functionalized α-iodoesters. Allylic iodides are coupled with α-diazoesters in the presence of a copper catalyst and a ligand to generate iodonium ylides, which undergo metal-mediated rearrangements. By fine-tuning the structure of the ligand, we have reversed the regioselectivity of copper-catalyzed reactions of iodonium ylides from [2,3]- to [1,2]-rearrangements with the use of alternate bipyridine ligands. The preference for [1,2]-rearrangements was further improved by using bulky aryl α-diazoester substrates. Several α-iodoesters with a diverse range of functional groups were generated in good yields (up to 88% yield) and high regioselectivities (up to >95:5 regioisomeric ratio). A deuterium-labeled substrate was utilized to gain insight into the mechanism of the reaction.
- Xu, Bin,Gartman, Jackson A.,Tambar, Uttam K.
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p. 4150 - 4159
(2017/06/29)
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- Gold(I)/Chiral N,N′-Dioxide–Nickel(II) Relay Catalysis for Asymmetric Tandem Intermolecular Hydroalkoxylation/Claisen Rearrangement
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A highly efficient asymmetric cascade reaction between alkynyl esters and allylic alcohols has been realized. Key to success was the combination of a hydroalkoxylation reaction catalyzed by a π-acidic gold(I) complex with a Claisen rearrangement catalyzed by a chiral Lewis acidic N,N′-dioxide–nickel(II) complex. A range of acyclic α-allyl β-keto esters were synthesized in high yields (up to 99 %) with good diastereoselectivities (up to 97:3) and excellent enantioselectivities (up to 99 % ee) under mild reaction conditions. These products can be easily transformed into optically active β-hydroxy esters, β-hydroxy acids, or 1,3-diols.
- Li, Jun,Lin, Lili,Hu, Bowen,Zhou, Pengfei,Huang, Tianyu,Liu, Xiaohua,Feng, Xiaoming
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supporting information
p. 885 - 888
(2017/01/13)
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- Efficient Pd-Catalyzed Regio- and Stereoselective Carboxylation of Allylic Alcohols with Formic Acid
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Formic acid is efficiently used as a C1 source to directly carboxylate allylic alcohols in the presence of a low loading of palladium catalyst and acetic anhydride as additive to afford β,γ-unsaturated carboxylic acids with excellent chemo-, regio-, and stereoselectivity. The reaction proceeds through a carbonylation process with in situ-generated carbon monoxide under mild conditions, avoiding the use of high-pressure gaseous CO. A bisphosphine ligand with a large bite angle (4,5-bis{diphenylphosphino}-9,9-dimethylxanthene, Xantphos) was found to be uniquely effective for this transformation. The regio- and stereoconvergence of this reaction is ascribed to the thermodynamically favored isomerization of the allylic electrophile in the presence of the palladium catalyst.
- Fu, Ming-Chen,Shang, Rui,Cheng, Wan-Min,Fu, Yao
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supporting information
p. 8818 - 8822
(2017/07/11)
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- Novel Inhibitors of Staphyloxanthin Virulence Factor in Comparison with Linezolid and Vancomycin versus Methicillin-Resistant, Linezolid-Resistant, and Vancomycin-Intermediate Staphylococcus aureus Infections in Vivo
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Our previous work (Wang et al. J. Med. Chem. 2016, 59, 4831-4848) revealed that effective benzocycloalkane-derived staphyloxanthin inhibitors against methicillin-resistant Staphylococcus aureus (S. aureus) infections were accompanied by poor water solubility and high hERG inhibition and dosages (preadministration). In this study, 92 chroman and coumaran derivatives as novel inhibitors have been addressed for overcoming deficiencies above. Derivatives 69 and 105 displayed excellent pigment inhibitory activities and low hERG inhibition, along with improvement of solubility by salt type selection. The broad and significantly potent antibacterial spectra of 69 and 105 were displayed first with normal administration in the livers and hearts in mice against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate S. aureus), and NRS271 (linezolid-resistant S. aureus), compared with linezolid and vancomycin. In summary, both 69 and 105 have the potential to be developed as good antibacterial candidates targeting virulence factors.
- Ni, Shuaishuai,Wei, Hanwen,Li, Baoli,Chen, Feifei,Liu, Yifu,Chen, Wenhua,Xu, Yixiang,Qiu, Xiaoxia,Li, Xiaokang,Lu, Yanli,Liu, Wenwen,Hu, Linhao,Lin, Dazheng,Wang, Manjiong,Zheng, Xinyu,Mao, Fei,Zhu, Jin,Lan, Lefu,Li, Jian
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supporting information
p. 8145 - 8159
(2017/10/18)
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- Chiral Br?nsted Acid Catalyzed Enantioselective Phosphonylation of Allylamine via Oxidative Dehydrogenation Coupling
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A new strategy for the synthesis of chiral α-amino phosphonates by enantioselective C-H phosphonylation of allylamine with phosphite in the presence of a chiral Br?nsted acid catalyst has been developed. This protocol successfully integrates direct C-H oxidation with asymmetric phosphonylation and exhibits high enantioselectivity.
- Cheng, Ming-Xing,Ma, Ran-Song,Yang, Qiang,Yang, Shang-Dong
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supporting information
p. 3262 - 3265
(2016/07/13)
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- Synthesis of trifluoromethylated compounds from alcohols via alkoxydiphenylphosphines
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The transformation of hydroxyl group in benzyl or allyl alcohols to trifluoromethyl was achieved via the reaction of the corresponding alkyloxydiphenylphosphine and CuCF3, generated in situ from methyl fluorosulfonyldifluoroacetate and CuI, under mild conditions. A plausible mechanism was proposed on the basis of experimental results.
- Li, Jun-Li,Yang, Xian-Jin,Wang, Yanan,Liu, Jin-Tao
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supporting information
p. 254 - 259
(2015/09/02)
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- A Simple and Efficient Access to Naphtho[b]furans by Claisen Rearrangement/Cyclization of Bromonaphthyl 3-Phenylallyl Ethers
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A transition-metal-free Claisen rearrangement/cyclization reaction was developed for the synthesis of naphthofuran derivatives from bromonaphthyl 3-phenylallyl ethers. The nature of the base employed in this reaction plays an important role in determining the ratio for the formation of naphthofuran and naphthol products. By using K2CO3 as base and DMF as solvent, we have synthesized a variety of functionalized naphthofurans in good to high yields (49-92 %) and with satisfactory selectivities.
- Wang, Wei,Huang, Jin,Zhou, Rong,Jiang, Zhi-Jie,Fu, Hai-Yan,Zheng, Xue-Li,Chen, Hua,Li, Rui-Xiang
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supporting information
p. 2442 - 2446
(2015/08/18)
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- SULFAMATE DERIVATIVE COMPOUND FOR USE IN PREVENTING OR TREATING EPILEPSY
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The present invention relates to a pharmaceutical composition for treating or preventing epilepsy containing a sulfamate derivative compound and/or pharmaceutically acceptable salt thereof as an active ingredient. Furthermore, the present invention relates to a method for treatment or prevention epilepsy comprising administering a sulfamate derivative compound in a pharmaceutically effective amount to a subject in need of treatment or prevention of epilepsy.
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Page/Page column 13; 14
(2015/06/25)
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- PHENYLALKYL SULFAMATE COMPOUND AND MUSCLE RELAXANT COMPOSITION COMPRISING THE SAME
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The present invention relates to novel phenylalkyl sulfamate compounds, a method for preventing or treating a disease associated with muscle spasm. The present invention ensures the enhancement of muscle relaxation activity essential for alleviation of muscle spasm, such that it is promising for preventing or treating various diseases associated with muscle spasm.
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Page/Page column 16
(2014/01/08)
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- Synthesis of 1,3,5-trisubstituted pyrazolines via Zn(ii)-catalyzed double hydroamination of enynes with aryl hydrazines
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An efficient Zn(ii)-catalyzed intermolecular double hydroamination of 1,3-enynes with aryl hydrazines, for the synthesis of pyrazolines, has been discussed.
- Patil, Nitin T.,Singh, Vipender
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p. 11116 - 11118
(2011/11/29)
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- Inhibition of chitin synthases and antifungal activities by 2′-benzoyloxycinnamaldehyde from Pleuropterus ciliinervis and its derivatives
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In the course of search for potent chitin synthase inhibitors from natural resources, a novel chitin synthases inhibitor, 2′-benzoyloxycinnamaldehyde (2′-BCA) (I), was isolated from the aerial parts of Pleuropterus ciliinervis NAKAI. 2′-BCA inhibited chit
- Kang, Tae Hoon,Hwang, Eui Il,Yun, Bong Sik,Park, Ki Duk,Kwon, Byoung Mog,Shin, Chul Soo,Kim, Sung Uk
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p. 598 - 602
(2008/02/02)
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- 1-Cinnamyl-4-(2-methoxyphenyl)piperazines: Synthesis, binding properties, and docking to dopamine (D2) and serotonin (5-HT1A) receptors
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Clinical properties of atypical antipsychotics are based on their interaction with D2 dopamine receptor and serotonin 5-HT1A and 5-HT2A receptors. As a part of our research program on new antipsychotics, we synthesized various derivatives of 1-cinnamyl-4-(2- methoxyphenyl)piperazines, and evaluated their affinities for D2, 5-HT1A, 5-HT2A, and adrenergic (α1) receptors using radioligand-binding assays. In addition, we performed docking analysis using models for the D2 and 5-HT1A receptors. All compounds exhibited low to moderate affinity to 5-HT1A and 5-HT 2A receptors, high affinity to the D2 receptor and large variability in affinities for the α1 receptor. Docking analysis indicated that the binding to D2 and 5-HT1A receptors is based on (i) interaction between protonated N1 of the piperazine ring and various aspartate residues, (ii) hydrogen bonds between various moieties of the ligand and the residues of threonine, serine, histidine or tryptophane, and (iii) edge-to-face interactions of the aromatic ring of the arylpiperazine moiety with phenylalanine or tyrosine residues. Docking data for the D 2 receptor can account for the binding properties obtained in binding assays, suggesting that the model is reliable and robust. However, docking data for the 5-HT1A receptor cannot account for actual binding properties, suggesting that further refinement of the model is required.
- Penjisevic, Jelena,Sukalovic, Vladimir,Andric, Deana,Kostic-Rajacic, Sladjana,Soskic, Vukic,Roglic, Goran
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p. 456 - 465
(2008/12/21)
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- Rhodium-catalyzed direct C-H addition of 3,4-dihydroquinazolines to alkenes and their use in the total synthesis of vasicoline
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The inter- and intramolecular couplings of unactivated alkenes to 3,4-dihydroquinazolines with a Rh(I) catalyst are reported. Coupling between olefins and NH-3,4-dihydroquinazoline was found to occur consecutively with heterocycle dehydrogenation in the p
- Wiedemann, Sean H.,Ellman, Jonathan A.,Bergman, Robert G.
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p. 1969 - 1976
(2007/10/03)
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- NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
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Disclosed herein are compounds of formula Ar1-X-W-Ar2 wherein Ar1 and Ar2 represent aryl groups characterized generally as aromatic heterocycles (e.g. imidazolyl or tetrazolyl) or carbocycles (e.g. phenyl or naphthalenyl); the aryl groups are optionally substituted or fused with other heterocycles or carbocycles; the aryl groups can bear substituents such as alkyl, halo or O-alkyl. X is a heteroatom, a valence bond or an optionally substituted divalent methylene, and W represents a spacer; typical spacers include divalent alkylene or alkylene-amido, -amido or -oxy radicals, which may optionally be substituted (e.g. hydroxyl or oxo). A typical compound is a derivative of 2-(N-napthalenyltetrazolylthio)- N-(2-nitrophenyl)acetamide. The compounds have inhibitory activity against Wild Type and single or double mutant strains of HIV.
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