- New coumarin-based fluorescent melatonin ligands. Design, synthesis and pharmacological characterization
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The design and synthesis of a series of new fluorescent coumarin-containing melatonin analogues is presented. The combination of high-binding affinities for human melatonergic receptors (h-MT1R and h-MT2R) and fluorescent properties, derived from the inclusion of melatonin pharmacophoric elements in the coumarin scaffold, yielded suitable candidates for the development of MT1R and MT2R fluorescent probes for imaging in biological media.
- De La Fuente Revenga, Mario,Herrera-Arozamena, Clara,Fernández-Sáez, Nerea,Barco, Gema,García-Orue, Itxaso,Sugden, David,Rivara, Silvia,Rodríguez-Franco, María Isabel
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Read Online
- Design, synthesis, biological evaluation, homology modeling and docking studies of (E)-3-(benzo[d][1,3]dioxol-5-ylmethylene) pyrrolidin-2-one derivatives as potent anticonvulsant agents
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A series of (E)-3-(benzo[d][1,3]dioxol-5-ylmethylene)pyrrolidin-2-one derivatives were designed, synthesized, and evaluated for their anticonvulsant activities. In the preliminary screening, compounds 5, 6a–6f and 6h–6i showed promising anticonvulsant activities in MES model, while 6f and 6g represented protection against seizures at doses of 100 mg/kg and 0.5 h in scPTZ model. The most active compound 6d had a high-degree protection against the MES-induced seizures with ED50 value of 4.3 mg/kg and TD50 value of 160.9 mg/kg after intraperitoneal (i.p.) injection in mice, which provided 6d in a high protective index (TD50/ED50) of 37.4 comparable to the reference drugs. Beyond that, 6d has been selected and evaluated in vitro experiment to estimate the activation impact. Apparently, 6d clearly inhibits the Nav1.1 channel. Our preliminary results provide new insights for the development of small-molecule activators targeting specifically Nav1.1 channels to design potential drugs for treating epilepsy. The computational parameters, such as homology modeling, docking study, and ADME prediction, were made to exploit the results.
- Wang, Tiantian,Dong, Shiyang,Chen, Xiaodong,Qian, Kun,Wang, Huayu,Quan, Hexiu,Zhang, Zhongli,Zuo, Yueming,Huang, Liping,Li, Dongxun,Yang, Ming,Yang, Shilin,Jin, Yi,Wang, Zengtao
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supporting information
p. 1324 - 1329
(2018/03/21)
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- Palladium-Catalyzed Hydroamidocarbonylation of Olefins to Imides
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Carbonylation reactions allow the efficient synthesis of all kinds of carbonyl-containing compounds. Here, we report a straightforward synthesis of various imides from olefins and CO for the first time. The established hydroamidocarbonylation reaction affords imides in good yields (up to 90%) and with good regioselectivity (up to 99:1) when applying different alkenes and amides. The synthetic potential of the method is highlighted by the synthesis of Aniracetam by intramolecular hydroamidocarbonylation.
- Li, Haoquan,Dong, Kaiwu,Neumann, Helfried,Beller, Matthias
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supporting information
p. 10239 - 10243
(2015/09/01)
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- CATALYSTS AND PROCESSES FOR THE HYDROGENATION OF AMIDES
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There is provided a process for the reduction of one or more amide moieties in a compound comprising contacting the compound with hydrogen gas and a transition metal catalyst in the presence or absence of a base under conditions for the reduction an amide bond. The presently described processes can be performed at low catalyst loading using relatively mild temperature and pressures, and optionally, in the presence or absence of a base or high catalyst loadings using low temperatures and pressures and high loadings of base to effect dynamic kinetic resolution of achiral amides.
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Paragraph 0181
(2014/06/24)
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- Chemoselective palladium-catalyzed oxidation of vinyl ether to acetate using hydrogen peroxide
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A practical and environmental-friendly method was developed to convert vinyl ether into acetate by using a palladium complex with phosphine ligand and hydrogen peroxide. The only by-product is water. Chemoselective oxidation of vinyl ether and tert-enamides to form acetate and N-acetyl amide with hydrogen peroxide in the presence of palladium complex having phosphine ligand was developed under mild reaction conditions. This process is environmentally friendly because it uses hydrogen peroxide as a clean oxidant, with water being the only byprocuct.
- Kon, Yoshihiro,Tanaka, Shinji,Nakashima, Takuya,Sato, Kazuhiko,Shimada, Hiromichi
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p. 749 - 756
(2014/07/22)
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- Structural modifications of (Z)-3-(2-aminoethyl)-5-(4-ethoxybenzylidene) thiazolidine-2,4-dione that improve selectivity for inhibiting the proliferation of melanoma cells containing active ERK signaling
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We herein report on the pharmacophore determination of the ERK docking domain inhibitor (Z)-3-(2-aminoethyl)-5-(4-ethoxybenzylidene)thiazolidine-2,4- dione, which has led to the discovery of compounds with greater selectivities for inhibiting the proliferation of melanoma cells containing active ERK signaling. The Royal Society of Chemistry 2013.
- Jung, Kwan-Young,Samadani, Ramin,Chauhan, Jay,Nevels, Kerrick,Yap, Jeremy L.,Zhang, Jun,Worlikar, Shilpa,Lanning, Maryanna E.,Chen, Lijia,Ensey, Mary,Shukla, Sagar,Salmo, Rosene,Heinzl, Geoffrey,Gordon, Caryn,Dukes, Troy,MacKerell Jr., Alexander D.,Shapiro, Paul,Fletcher, Steven
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p. 3706 - 3732
(2013/07/05)
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- Oxidative transformation of cyclic ethers/amines to lactones/lactams using a DIB/TBHP protocol
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A novel C-H oxidation of cyclic ethers and amines to the corresponding lactones and lactams was developed using a DIB/TBHP protocol. The reaction is mild and no metallic reagent is involved. In addition, study shows that the electronic properties of the substituents could affect the selectivity of oxidation. The Royal Society of Chemistry 2013.
- Zhao, Yi,Ang, Jascelyn Qian Lin,Ng, Angela Wan Ting,Yeung, Ying-Yeung
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p. 19765 - 19768
(2013/11/06)
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- Biomimetic aerobic oxidation of amino alcohols to lactams
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The right path: N-Protected amino alcohols undergo aerobic and biomimetic oxidation to the corresponding lactams in the presence of a ruthenium catalyst and a combination of electron-transfer mediators under air (see scheme). The reaction was used for the synthesis of five-, six-, and seven-, membered lactams and showed good tolerance to a number of N-protecting groups. Copyright
- Babu, Beneesh P.,Endo, Yoshinori,Baeckvall, Jan-E.
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supporting information
p. 11524 - 11527,4
(2012/12/11)
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- A highly active catalyst for the hydrogenation of amides to alcohols and amines
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Amide-zing: The reaction between 2 equivalents of Ph2P(CH 2)2NH2 and cis-[Ru(CH3CN) 2(η3-C3H5)(cod)]BF4 (cod=1,5-cyclooctadiene) forms a highly active catalyst precursor for the selective hydrogenation of amides. The reaction proceeds with excellent atom economy, yield, and turnover numbers (TONs) under moderate reaction conditions. The technology offers a greener, practical approach to the use of metal hydride reagents commonly employed in both academia and industry. Copyright
- John, Jeremy M.,Bergens, Steven H.
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supporting information; experimental part
p. 10377 - 10380
(2011/12/04)
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- Iridium-catalyzed highly enantioselective hydrogenation of exocyclic α,β-unsaturated carbonyl compounds
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By using the iridium complex of a phosphine-oxazoline ligand with an axis-unfixed biphenyl backbone, a highly enantioselective hydrogenation of the C=C bond of exocyclic α,β-unsaturated carbonyl compounds to afford α-chiral cyclic ketones, lactones and lactams was developed.
- Tian, Fengtao,Yao, Dongmei,Liu, Yuanyuan,Xie, Fang,Zhang, Wanbin
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supporting information; experimental part
p. 1841 - 1845
(2010/10/21)
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- Rhodanine derivatives as novel inhibitors of PDE4
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The discovery, synthesis and in vitro activity of a novel series of rhodanine based phosphodiesterase-4 (PDE4) inhibitors is described. Structure-activity relationship studies directed toward improving potency led to the development of submicromolar inhibitors 2n and 3i (IC50 = 0.89 & 0.74 μM). The replacement of rhodanine with structurally related heterocycles was also investigated and led to the synthesis of pseudothiohydantoin 7 (IC50 = 0.31 μM).
- Irvine, Mark W.,Patrick, Graham L.,Kewney, Justin,Hastings, Stuart F.,MacKenzie, Simon J.
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p. 2032 - 2037
(2008/12/21)
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- 11C-LABELED BENZYL-LACTAM COMPOUNDS AND THEIR USE AS IMAGING AGENTS
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The invention relates to ""C-labeled compounds, their preparation, compositions comprising an effective amount of a ""C-labeled compound, and the use of a ""C-labeled compound as a radiopharmaceutical for positron emission tomography.
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Page/Page column 21
(2008/06/13)
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- Toward Transition Metal-Catalyzed Carbonylation of Methanol without HI as Copromoter: Catalytic Exocyclic Carbonylation of Cycloimino Esters
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(Formula presented). Initial studies of a rare exocyclic C-O bond carbonylation are reported. Under the catalysis of Co2(CO) 8 in the absence of HI as the copromoter, cycloimino esters are carbonylated to afford N-acyllactams in high yields under relatively mild conditions (100-160°C and 200-1000 psi). The reaction is interesting because it opens up the possibility of carbonylation of alcohols in the absence of HI.
- Xu, Hongyu,Jia, Li
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p. 3955 - 3957
(2007/10/03)
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- Palladium(II)-mediated oxidative cyclization of N-carbamoyl aminoalkynes: A new route to γ-lactams
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Transformation of N-carbamoyl or acetyl-4-trimethylsilyl-3-alkyn-1-amines to diversely substituted 2-pyrrolidinones, via a Wacker-type reaction, is described.
- Doan, Huynh Dong,Gore, Jacques,Vatele, Jean-Michel
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p. 6765 - 6768
(2007/10/03)
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- Synthesis and anticonvulsant activity of 1-acyl-2-pyrrolidinone derivatives
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Several 1-acyl-2-pyrrolidinone derivatives were synthesized as derivatives of γ-aminobutyric acid (GABA), and their pharmacological activities and stabilities were investigated. The derivatives showed anticonvulsant effect on picrotoxin-induced seizure at a dose of 200 mg/kg. In particular, 1-decanoyl-2-pyrrolidinone (7) and 1-dodecanoyl-2-pyrrolidinone (8) had a high activity. The anticonvulsant activity showed a dose dependency. Some of 1-acyl-2-pyrrolidinone derivatives prolonged sleeping time which was induced by sodium pentobarbital and showed a recovery from disruption of the memory of passive avoidance response, which was induced by an electroconvulsive shock. As shown by the results of the stability study of 1-acetyl-2-pyrrolidinone (1), it was degraded in an acidic buffer and an alkaline buffer although 2-pyrrolidinone was stable. 1-Acyl-2-pyrrolidinone derivatives were degraded in liver and brain homogenates of mouse and rat. They showed a degradation rate in rat plasma. Conversion of 8 to GABA in mouse liver homogenate was demonstrated. These results suggested that the pharmacological activity of 1-acyl-2-pyrrolidinone is probably due to the release of GABA by hydrolysis of derivatives although further work is necessary.
- Sasaki,Mori,Nakamura,Shibasaki
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p. 628 - 633
(2007/10/02)
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- A Convenient Synthesis of 2-Methyl/ethyl-Δ1-pyrrolines
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2-Methyl/ethyl-Δ1-pyrrolines have been conveniently synthesised from commercially available 2-pyrrolidone.
- Ananthapadmanabhan, S.,Raja, T. K.,Srinivasan, V.,Simon, A.
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- Anodic Oxidation of Amides and Lactams Using N-Hydroxyphthalimide as a Mediator
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Indirect electrochemical oxidation of amides and N-alkyllactams was performed using N-hydroxyphthalimide as a mediator.A carbonyl group was introduced in good yield at the α-carbon to the nitrogen of the compounds.Keywords - anodic oxidation; mediator; amide; N-alkyllactam; N-hydroxyphthalimide; imide; N-acyllactam; glassy-carbon electrode
- Masui, Masaichiro,Hara, Seijiro,Ozaki, Shigeko
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p. 975 - 979
(2007/10/02)
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- PHOTOCHEMISTRY OF THE SEMICYCLIC IMIDE SYSTEM. I EVIDENCE FOR COMPETITIVE TYPE I AND TYPE II PROCESSES
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Photolyses of a series of N-acylpyrrolidones (4) show that semicyclic imides are capable of undergoing competitive type I and type II processes.
- Machida, Minoru,Takechi, Haruko,Sakushima, Akiyo,Kanaoka, Yuichi
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p. 479 - 480
(2007/10/02)
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