- Synthesis and characterization of DOTA-mono-adamantan-1-ylamide
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A novel chelator of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) functionalized by adamantane was synthesized by nucleophilic substituted reaction of 1,4,7-Tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane (5) and N-(adamantan-1-yl) bromoacetamide (2). The intermediates and target compound (7) were characterized by fourier transform infrared spectroscopy (FT-IR), 1H nuclear magnetic resonance (NMR), 13C NMR, atmospheric-pressure ionization electrospray mass spectrometry (API-ES-MS), and elemental analysis.
- Wan, Fuxian,Liu, Mingjie,Zhang, Junzheng,Li, Ying,Jiang, Lin
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Read Online
- Design, synthesis, and evaluation of fimbrolide-nitric oxide donor hybrids as antimicrobial agents
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Fimbrolides from marine algae have shown promising activity against quorum sensing (QS), a chief regulatory and communication system in bacteria controlling biofilm formation and virulence factor. Nitric oxide (NO) at sublethal concentration has also been reported to induce dispersal of bacterial biofilms and increase their susceptibility toward standard biocides and antibiotics. Therefore, the combination of QS inhibitors and NO donors has the potential to control the development of biofilm and promote their dispersion via a nonbactericidal mechanism. Inspired by these ideas, novel fimbrolide-NO donor hybrid compounds were designed and synthesized. Fimbrolide-NO hybrids 6b, 6f, and 14a were found to be particularly effective as antimicrobials compared to the nonhybrid natural fimbrolides as revealed by bioluminescent P. aeruginosa QS reporter assays and biofilm inhibition assays. Significantly, these fimbrolide-NO hybrids represent the first dual-action antimicrobial agent based on the baterial QS inhibition and NO signaling.
- Kutty, Samuel K.,Barraud, Nicolas,Pham, Amy,Iskander, George,Rice, Scott A.,Black, David Stc.,Kumar, Naresh
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Read Online
- Gemfibrozil derivatives as activators of soluble guanylyl cyclase – A structure-activity study
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Previous studies demonstrated that anti-hyperlipidemic drug gemfibrozil acts as NO- and heme-independent activator of NO receptor soluble guanylyl cyclase. A series of new gemfibrozil derivatives were synthesized and evaluated for sGC activation. The structure-activity relationship study identified the positions in gemfibrozil's scaffold that are detrimental for sGC activation and those that are amendable for optimizing modifications. Compared with gemfibrozil, compounds 7c and 15b were more potent activators of cGMP-forming activity of purified sGC and exhibited enhanced relaxation of preconstricted mouse thoracic aorta rings. These studies established the overall framework needed for futher improvement of sGC activators based on gemfibrozil scaffold.
- Baker, Hannah,Ferreira, Liam D.,Gayler, Kevin M.,Kane, Robert R.,Karunananthan, Johann W.,Kostyo, Jessica H.,Martin, Emil,Mattke, Jordan,Nguyen, Harold,Plunk, Michael A.,Quintana, Jeremy M.,Sharina, Iraida,Shuda, Mina,Stinchcomb, Alexandra L.
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- Synthesis and Fungitoxic Evaluation of Acylamino-1,2,4-Triazoles
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Ten different acylamino-1,2,4-triazoles were prepared by the reaction of differently substituted benzoyl chlorides and acetyl chlorides with 4-amino-1,2,4-triazole using catalytic amount of triethylamine. The synthesized compounds were characterized using UV, 1H-nuclear magnetic resonance spectroscopy, and infrared spectroscopy. All the compounds were tested for their fungicidal potential against three fungal species, that is, Fusarium verticillioides, Macrophomina phaseolina, and Rhizoctonia solani using poisoned food technique. The synthesized compounds were tested at various concentrations along with standard carbendazim 50 WP. The amides synthesized by reaction of substituted benzoyl chlorides and 4-amino-1,2,4-triazole exhibited greater fungicidal activity against all the tested fungi as compared to the amides synthesized using substituted acetyl chlorides. Among all the tested compounds, 4-nitro-N-(4-H-1,2,4-triazol-4-yl)benzamide showed the maximum fungicidal activity with the least median effective dose (ED50) values of 100, 93, and 146 μg ml-1 against F verticillioides, M. phaseolina, and R. solani, respectively. All the compounds were found to be less effective than the standard used.
- Kaur, Gurinderjit,Kaur, Harleen,Kaur, Pardeep,Sharma, Sunita,Singh, Ravneet
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p. 389 - 395
(2021/11/22)
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- POMALIDOMIDE DERIVATIVE AND PREPARATION METHOD THEREFOR
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Disclosed in the present invention are a Pomalidomide derivative and a preparation method therefor. Specifically, the present invention relates to the Pomalidomide derivative and a stereoisomer thereof, or a pharmaceutically acceptable salt, and applications thereof in the preparation of drugs for treating cancers.
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Paragraph 0112-0113
(2020/07/14)
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- Design, synthesis and biological evaluation of novel acetamide-substituted doravirine and its prodrugs as potent HIV-1 NNRTIs
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A novel series of acetamide-substituted derivatives and two prodrugs of doravirine were designed and synthesized as potent HIV-1 NNRTIs by employing the structure-based drug design strategy. In MT-4 cell-based assays using the MTT method, it was found that most of the new compounds exhibited moderate to excellent inhibitory potency against the wild-type (WT) HIV-1 strain with a minimum EC50 value of 54.8 nM. Among them, the two most potent compounds 8i (EC50 = 59.5 nM) and 8k (EC50 = 54.8 nM) displayed robust activity against WT HIV-1 with double-digit nanomolar EC50 values, being superior to lamivudine (3TC, EC50 = 12.8 μM) and comparable to doravirine (EC50 = 13 nM). Besides, 8i and 8k shown moderate activity against the double RT mutant (K103N + Y181C) HIV-1 RES056 strain. The HIV-1 RT inhibition assay further validated the binding target. Molecular simulation of the representative compounds was employed to provide insight on their structure-activity relationships (SARs) and direct future design efforts. Finally, the aqueous solubility and chemical stability of the prodrugs 9 and 10 were investigated in detail.
- Wang, Zhao,Yu, Zhao,Kang, Dongwei,Zhang, Jian,Tian, Ye,Daelemans, Dirk,De Clercq, Erik,Pannecouque, Christophe,Zhan, Peng,Liu, Xinyong
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p. 447 - 456
(2019/01/04)
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- POMALIDOMIDE DERIVATIVES AND THE PREPARING METHOD THEREOF
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The invention relates to pomalidomide derivatives and their stereoisomers or pharmaceutically acceptable salts, and their use in preparing medicaments for treating cancers.
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Paragraph 0102-0104
(2019/08/01)
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- Isoalantolactone derivative, pharmaceutical composition and application thereof
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The invention relates to an isoalantolactone derivative, a pharmaceutical composition and application thereof, especially use of the isoalantolactone derivative shown as formula (I) or a salt pharmaceutical compound thereof in preparation of adjuvant drugs treating cancer, a pharmaceutical composition containing a therapeutically effective amount of isoalantolactone derivative (I) or its salt anda pharmaceutically acceptable carrier or a composition with other anticancer drugs.
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Paragraph 0014
(2019/02/02)
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- Design, synthesis and biological study of potent and covalent HER-2 tyrosine kinase inhibitors with low cytotoxicity in vitro
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The discovery and development of a novel HER-2 tyrosine kinase inhibitor for the treatment of HER2-positive breast cancer are presented in this article. EGFR family has been recognized as a crucial meditator in the cancer progression; HER-2 tyrosine kinase was one of the members among them. In the effort to explore potent HER-2 inhibitors, a novel series of 4-anilino-3-cyanoquinoline derivatives have been designed, synthesized and evaluated. Most compounds possessed modest proliferation inhibition on SK-BR-3 cell line and HER-2 kinase. Compound 16 appeared to be the most potent compound (HER-2 kinase IC50: 19.4?nM, SK-BR-3 IC50: 94?nM). In the experiment of cellular cytotoxicity assay, compound 16 shows a much lower cytotoxicity than neratinib on Beas-2b cell line (Human bronchial epithelial cells). In conclusion, compound 16 would be a promising lead compound for further anti-breast cancer drug discovery.
- Jin, Shuyu,Sun, Xiuyun,Liu, Dan,Xie, Hua,Rao, Yu
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p. 1333 - 1345
(2019/05/06)
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- GluN2B subunit targeting central nervous system positron tracer and preparation thereof
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The existing GluN2B selective positron tracer has relatively high affinity and selectivity, but does not show ideal tracer properties in an in vivo experiment, has the problems of overquick metabolism, lower brain uptake, undifferentiated distribution in the whole brain, overquick degradation of C-11 labeled probe and off-target phenomenon caused by influence of other target spots in the brain, which limit the further translational research. The invention designs a novel GluN2B subunit targeting central nervous system positron tracer, reduces the metabolism rate of the tracer and prolongs theservice time by utilizing the characteristics that a methylamino structure is stable and not easy to metabolize. Meanwhile, the tracer of the invention is easy to be detected and traced through experiments, and has a better electron tracing effect. In addition, a preparation method provided by the invention is mild in conditions, and can quickly obtain a high-purity C11-labeled tracer injection,so as to effectively solve the problem of overquick degradation of the C-11 labeled probe.
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Paragraph 0030-0034; 0042; 0045-0047
(2019/10/15)
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- Discovery of a Small-Molecule Inhibitor of Interleukin 15: Pharmacophore-Based Virtual Screening and Hit Optimization
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Interleukin (IL)-15 is a pleiotropic cytokine, which is structurally close to IL-2 and shares with it the IL-2 β and γ receptor (R) subunits. By promoting the activation and proliferation of NK, NK-T, and CD8+ T cells, IL-15 plays important roles in innate and adaptative immunity. Moreover, the association of high levels of IL-15 expression with inflammatory and autoimmune diseases has led to the development of various antagonistic approaches targeting IL-15. This study is an original approach aimed at discovering small-molecule inhibitors impeding IL-15/IL-15R interaction. A pharmacophore and docking-based virtual screening of compound libraries led to the selection of 240 high-scoring compounds, 36 of which were found to bind IL-15, to inhibit the binding of IL-15 to the IL-2Rβ chain or the proliferation of IL-15-dependent cells or both. One of them was selected as a hit and optimized by a structure-activity relationship approach, leading to the first small-molecule IL-15 inhibitor with sub-micromolar activity.
- Quéméner, Agnès,Maillasson, Mike,Arzel, Laurence,Sicard, Benoit,Vomiandry, Romy,Mortier, Erwan,Dubreuil, Didier,Jacques, Yannick,Lebreton, Jacques,Mathé-Allainmat, Monique
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supporting information
p. 6249 - 6272
(2017/08/02)
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- Design, synthesis and in vitro evaluation of amidoximes as histone deacetylase inhibitors for cancer therapy
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Amindoximes are geometric isomers of N-hydroxyamidines which are bioisosteres of hydroxamates. Since amindoxime group is capable of chelating transition metal ions including zinc ion, amindoximes should possess histone deacetylases (HDACs) inhibitory activity. In this work, we designed and synthesized a series of amindoximes, examined their inhibitory activities against HDACs, and investigated their cytotoxicity to human cancer cells. Preliminary results demonstrated that amindoximes possessed submicromolar HDACs inhibitory activity, with noteworthy enhancement compared with hydroxamates. Furthermore, the amindoximes arrested HCT116 and A549 cells in G2/M phase and showed good efficacy in inducing cells death. We provided a proof-of-concept that amindoximes could be used as HDACs inhibitors and hold great promise as epigenetic drugs.
- Jiao, Peifu,Jin, Peng,Li, Chencan,Cui, Lechao,Dong, Lihua,Pan, Bin,Song, Wentong,Ma, Liang,Dong, Jinlong,Song, Lei,Jin, Xinjie,Li, Faming,Wan, Maosheng,Lv, Zhitao,Geng, Qiaohong
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supporting information
p. 4679 - 4683
(2016/09/13)
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- Highly efficient preparation of selectively isotope cluster-labeled long chain fatty acids via two consecutive Csp3-Csp3 cross-coupling reactions
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An efficient synthesis involving two copper-catalyzed alkyl-alkyl coupling reactions has been designed to easily access doubly isotope-labeled fatty acids. Such NMR- and IR-active compounds were obtained in excellent overall yields and will be further used for determining the conformation of an alkyl chain of lipidic biomolecules upon interaction with proteins.
- Lethu, Sebastien,Matsuoka, Shigeru,Murata, Michio
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supporting information
p. 844 - 847
(2014/03/21)
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- Microwave-assisted synthesis of N -isobutyl-4,5-epoxy-2(E)-decenamide
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A new and efficient synthesis of a naturally occurring amide alkaloid, N-isobutyl-4,5-epoxy-2(E)-decenamide isolated from the roots of Piper nigrum has been described involving a total of nine steps. Octanal and 2-bromoacetic acid have been used as the starting materials.
- Gupta, Neeraj,Kaur, Manvinder,Shallu,Gupta, Neeru,Kad, Goverdhan Lal,Singh, Jasvinder
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p. 548 - 553
(2013/05/21)
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- Synthesis, DNA photocleavage and singlet oxygen measurement of cationic bisporphyrins
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With.OCH2CO. as a linker, a non β-substituted cationic bisporphyrin (4a) and a β-substituted cationic bisporphyrin (4b) were prepared through methylation of the intermediate which was obtained from β-amino-5,10,15,20- tetra (4-cyanophenyl) porphyrin or 5-hydroxylphenyl-10,15,20-tris(4-cyanophenyl) reacting with 5-hydroxy-10,15,20-trispyridinylporphyrin. Their structures were confirmed by 1H NMR, IR, UV-vis, MS and elemental analysis. DNA photocleavage ability and the singlet oxygen ability of those cationic bisporphyrins were investigated. DNA photocleavage activity of β-substituted cationic bisporphyrin was significantly weaker than that of H2TMPyP, but similar to that of non β-substituted cationic bisporphyrin. While 4a and 4b showed substantial photocleavage activities toward DNA, with 68% and 66% observed at 10 μM. The assessment of indirectly measured 1O2 production rates against H2TMPyP were described and the relative singlet oxygen production yields were: free cationic bisporphyrins 2TMPyP. The results showed the cationic bisporphyrins with β-substitution and non β-substitution could be developed as potential photodynamic agents.
- Wang, Kai,Jin, Qi,Zhang, Xiulan,Song, Shuai-Hua
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p. 246 - 251
(2013/07/26)
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- Active conformation of seven-membered-ring benzolactams as new ACAT inhibitors: Latent chirality at N5 in the 1,5-benzodiazepin-2-one nucleus
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Nitrogen chirality: Potent new ACAT inhibitors with seven-membered-ring benzolactams as the core structures were first prepared, and the axial chirality recognized by the enzyme was clarified (e.g., 1; see scheme). The chirality at the axis (aS) of 1 controls the conformation of the entire lactam ring, causing the N5-CH3 to arrange in a pseudo-equatorial position (i.e., the amine at N5 is a chiral center with the S-configuration) both in the crystal state and in solution. Copyright
- Tabata, Hidetsugu,Wada, Naoya,Takada, Yuko,Nakagomi, Jun,Miike, Tomohiro,Shirahase, Hiroaki,Oshitari, Tetsuta,Takahashi, Hideyo,Natsugari, Hideaki
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supporting information; experimental part
p. 1572 - 1576
(2012/04/10)
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- Consequences of linker length alteration of the α7 nicotinic acetylcholine receptor (nAChR) agonist, SEN12333
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A series of ligands based on SEN12333, containing either contracted or elongated alkyl chains, were synthesized and evaluated in molecular docking studies against a homology model of the α7 nicotinic acetylcholine receptor (nAChR) subtype. The predicted binding of all ligands was highly similar, with the exception of the analog containing a 5 methylene unit spacer. However, in vitro competition binding assays revealed that the ligands possessed dissimilar binding affinities, with a Ki range of more than an order of magnitude (Ki = 0.50 to >10 μM), and only SEN12333 itself exhibited functional activity at the α7 nAChR.
- Beinat, Corinne,Banister, Samuel D.,Van Prehn, Saundra,Doddareddy, Munikumar Reddy,Hibbs, David,Sako, Michael,Chebib, Mary,Tran, Thao,Al-Muhtasib, Nour,Xiao, Yingxian,Kassiou, Michael
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supporting information; experimental part
p. 2380 - 2384
(2012/05/05)
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- PYRROLOPYRIDINEAMINO DERIVATIVES AS MPS1 INHIBITORS
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The present invention relates to the use of certain pyrrolopyridineamino derivatives (hereinafter referred to as "PPA derivatives"), particularly 1H-pyrrolo[3,2-c]pyridine-6- amino derivatives, to inhibit the spindle checkpoint function of Monospindle 1 (Mps1 – also known as TTK) kinases either directly or indirectly via interaction with the Mps kinase itself. In particular, the present invention relates to PPA derivatives for use as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of the PPA derivatives, and pharmaceutical compositions comprising them. Formula (I)
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Page/Page column 95
(2012/10/07)
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- The discovery of a novel series of glucokinase activators based on a pyrazolopyrimidine scaffold
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Glucokinase is a key enzyme in glucose homeostasis since it phosphorylates glucose to give glucose-6-phosphate, which is the first step in glycolysis. GK activators have been proven to lower blood-glucose, and therefore have potential as treatments for type 2 diabetes. Here the discovery of pyrazolopyrimidine GKAs is reported. An original singleton hit from a high-throughput screen with micromolar levels of potency was optimised to give compounds with nanomolar activities. Key steps in this success were the introduction of an extra side-chain, which increased potency, and changing the linking functionality from a thioether to an ether, which led to improved potency and lipophilic ligand efficiency. This also led to more stable compounds with improved profiles in biological assays.
- Bonn, Peter,Brink, D. Mikael,F?gerhag, Jonas,Jurva, Ulrik,Robb, Graeme R.,Schnecke, Volker,Svensson Henriksson, Anette,Waring, Michael J.,Westerlund, Christer
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supporting information
p. 7302 - 7305
(2013/02/23)
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- Polyunsaturated alkyl amides from echinacea: Synthesis of diynes, enynes, and dienes
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The synthesis of 20 alkyl amides, including 15 naturally occurring polyunsaturated alkyl amides previously identified from Echinacea spp. (1-13 and 62) or from Achilla sp. (55) and five previously unknown geometric isomers (23, 28, 67, 73, and 80), is described. Importantly, these amides include all of the major alkyl amides present in commercially used Echinacea extracts. The syntheses demonstrate methodology used for constructing alkyl amides containing conjugated diyne and isomerically pure enyne and diene moieties and may be adapted easily for the preparation of other alkyl amides present in Echinacea spp. Terminal-conjugated diynes were prepared by a Cadiot-Chodkiewitz coupling/deprotection sequence utilizing a protected bromoacetylene, and methyl-substituted diynes were made via a base-catalyzed rearrangement of terminal-skipped diynes. Conjugated dienes were prepared conveniently and with high stereoselectivity by the reduction of enynes or diynes with Rieke zinc. With the exception of 1-2 and 11-12, the alkyl amides are synthesized here for the first time, and their NMR data are consistent with that of the reported isolated natural compounds.
- Matovic, Nicholas J.,Hayes, Patricia Y.,Penman, Kerry,Lehmann, Reginald P.,De Voss, James J.
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scheme or table
p. 4467 - 4481
(2011/07/30)
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- The photoinduced electron transference of porphyrin-anthraquinone dyads bridged with different lengths of links
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The photoinduced electron transference (PET) interaction in porphyrin containing donor-acceptor (D-A) molecules is of great importance in nature and a significant part of the PET research has been devoted to the study of its mechanism ("through-space" or "through-bond") in these decades. Herein we synthesized a series of covalently linked porphyrin-anthraquinone dyads (Por-Cn-AQ) bridged with flexible alkoxy chains at different lengths (n = 1, 4, 10) and investigated their intramolecular PET using a combination of electronic absorption, steady-state fluorescence and decayed luminescence spectra. The experimental results show that the PET efficiency depends on the length of the flexible linkage between the porphyrin and anthraquinone moieties. Meanwhile, theoretical calculation applying the density functional theory (DFT) was also carried out to give the frontier orbital distribution and the optimized structures of these dyads. It is found that the orientation of the dyad with high PET efficiency is disadvantageous to π-π interaction. Thus, the PET of these dyads seemingly is best compatible with a "through-bond" (superexchange) mechanism.
- Zhao, Ping,Huang, Jin-Wang,Xu, Lian-Cai,Ma, Li,Ji, Liang-Nian
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experimental part
p. 437 - 442
(2011/03/21)
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- Quantification of CH...π interactions: Implications on how substituent effects influence aromatic interactions
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Attractive interactions between a substituted benzene ring and an α-substituted acetate group were determined experimentally by using the triptycene model system. The attractive interaction correlates well with the Hammett constants σm (R2=0.90), but correlates much better with the acidity of the α-protons (R2=0.98). A predominant CH...π interaction was found to control the conformational preference of model compounds 1a-g. Despite the predominance of the CH...π interaction in compounds 1a-g, a Hammett plot displays a fairly straight line for the substituent effect. These results show that when using Hammett plots in a simplified model system, a system designed to study the effect of X...π interactions could capture the X-H...π interaction instead.
- Gung, Benjamin W.,Emenike, Bright U.,Lewis, Michael,Kirschbaum, Kristin
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supporting information; experimental part
p. 12357 - 12362
(2010/12/25)
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- Comparative reactivity of N′-(5-benzoyl/ethoxycarbonyl)thiazol-2-yl- N,N-dimethylformamidines with ketenes
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The comparative account of the reactivities of N′-[(5-benzoyl and ethoxycarbonyl)thiazol-2-yl]-N,N-dimethylformamidines (1a and 1b), tremendously influenced by the electronic nature of the substituents on C-5 of the thiazolic ring with various monosubstituted and conjugated ketenes is reported herein. The DA cycloadditions of the dienyl pyrimidinone 3h with both symmetrical as well as unsymmetrical dienophiles leading to the formation of various thiazolic pyrimidinone derivatives are also reported.
- Singh, Parvesh,Marwaha, Alka,Singh, Harmeet,Mahajan, Mohinder P.
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p. 11999 - 12005
(2007/10/03)
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- Esters derived from vanillin and vanillal and aromatic and functionalized aliphatic carboxylic acids
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Reactions of vanillin and vanillal with aromatic and functionally substituted aliphatic carboxylic acid chlorides in the presence of pyridine afforded the corresponding previously unknown esters.
- Dikusar,Kozlov
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p. 992 - 996
(2007/10/03)
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- Unsymmetrical DNA cross-linking agents: Combination of the CBI and PBD pharmacophores
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A set of 10 compounds, each combining the seco-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (seco-CBI) and pyrrolo [2,1-c] [1,4] benzodiazepine (PBD) pharmacophores, was designed and prepared. These compounds were anticipated to cross-link between N3 of adenine and N2 of guanine in the minor groove of DNA. The compounds, which differ in the chain length separating the two alkylation subunits, and the configuration of the CBI portion, showed great variation in cellular toxicity (over 4 orders of magnitude in a cell line panel) with the most potent example exhibiting IC50S in the pM range. Cytotoxicity correlated with the ability of the compounds to cross-link naked DNA. Cross-linking was also observed in living cells, at much lower concentrations than for a related symmetrical PBD dimer. A thermal cleavage assay was used to assess sequence selectivity, demonstrating that the CBI portion controlled the alkylation sites, while the PBD substituent increased the overall efficiency of alkylation. Several compounds were tested for in vivo activity using a tumor growth delay assay against WiDr human colon carcinoma xenografts, with one compound (the most cytotoxic and most efficient cross-linker) showing a statistically significant increase in survival time following a single iv dose.
- Tercel, Moana,Stribbling, Stephen M.,Sheppard, Hilary,Siim, Bronwyn G.,Wu, Kent,Pullen, Susan M.,Botting, K. Jane,Wilson, William R.,Denny, William A.
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p. 2132 - 2151
(2007/10/03)
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- 5-Hydroxy[1,2]oxazinan-3-ones as potential carbapenem and D-ala-D-ala surrogates
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The title compounds are amino acids whose nitrogen atom is enclosed in a six-membered cyclic hydroxamate bearing a C5-hydroxyl group. They belong to a proposed new family of antibacterial agents targeted to the penicillin receptor. The glycine and alanine members of the family have been synthesized, as racemates, in seven steps from the four-carbon synthon diketene and the tert-butyl esters of N-hydroxyglycine and N-hydroxyalanine. Numerous alternatives to diketene have also been examined, but these lead mainly to five-membered cyclic hydroxamates. The theoretical considerations that have led to this synthetic programme are discussed in some detail. They include analysis of the structures of natural and unnatural penicillin surrogates, analysis of the penicillin pharmacophore, and a treatment of the chemical reaction with which penicillin blocks bacterial cell wall synthesis. The glycine derivative exhibits marginal but real activity vs. Micrococcus luteus. The alanine derivative, which more closely resembles D-ala-D-ala, is fifty times more active. Two five-membered structural isomers of the glycine derivative are inactive.
- Wolfe, Saul,Akuche, Christiana,Ro, Stephen,Wilson, Marie-Claire,Kim, Chan-Kyung,Shi, Zheng
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p. 915 - 936
(2007/10/03)
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- Determination of regioselectivity in ring opening of tert-butylaziridinones by a combination of 15N labeling and electrospray ionization-ion trap mass spectrometry
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The ring opening of 1,3-di-tert-butylaziridinone by tert-butylamine and aniline was investigated by using electrospray ionization and collision-induced dissociation in an ion trap mass spectrometer in conjunction with 15N labeling of the two amine nucleophiles. Using the MSn capabilities of the ion trap instrument, we were able to monitor the retention of the 15N label through successive fragmentation steps. Both amines exhibited a remarkable degree of selectivity in that they both cleaved exclusively the 1,3-bond (the alkyl-nitrogen bond). This result is in contrast to that obtained previously with methylamine, which cleaved just the opposite bond, namely, the 1,2-bond (the acyl-nitrogen bond). These contrasting results could not have been predicted by previously published guidelines. Copyright
- Talaty,Van Stipdonk,Hague,Provenzano,Boese
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- FORMATION OF 6-ACYLINDOLES FROM 1-ACYLINDOLES
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1-Acylindoles react regioselectively with α-halogenoacyl chloride in the presence of aluminum chloride to produce 1-acyl-6-halogenoacylindoles in excellent yields.
- Nakatsuka, Shin-ishi,Teranishi, Katsunori,Goto, Toshio
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p. 2699 - 2700
(2007/10/02)
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- Efficient routes to isotopically labelled epichlorohydrins ((chloromethyl) oxiranes)
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Efficient routes are developed for the synthesis of variously labelled 2H- and 13C- labelled epichlorohydrins prepared from appropriately labelled acetic acids and sodium borodeuteride. The route is versatile and can be used for strategic location of isotopes at C-I, C-2 and C-3 of epichlorohydrin. By way of demonstration [2-13C]-, [2-2H]-, [3-2H2] and [2-2H, 3-2H2]-epithlorohydrins have been prepared. In addition the syntheses can be adapted for the preparation of enantiomerically pure and isotopically labelled epichlorohydrins.
- O'Hagan,White,Jones
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p. 871 - 880
(2007/10/02)
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- Syntheses and Physical Properties of Ferrocene Derivatives (II) Liquid Crystallinity and Multiple Melting Behavior of Ferrocene Derivatives
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Nine kinds of monosubstituted ferrocene derivatives, ω-alkyl 4-ferrocenylbenzoate, were prepared.The derivatives containing 4, 6, 10 and 11 carbon atoms in the flexible alkyl chain of the compounds showed liquid crystallinity, and multiple melting behavior was observed in the compounds containing 4, 6 and 11 carbon atoms.An appearance of the liquid crystallinity showed a carbon number dependence on the flexible alkyl chain. - Keywords: ferrocene, liquid crystal, multiple melting behavior, phase transition, transition metal complex
- Hanasaki, Tomonori,Ueda, Mitsunori,Nakamura, Naotake
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p. 329 - 336
(2007/10/02)
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- Optical brightening agents of naphthalimide derivatives
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A naphthalimide derivative having the formula STR1 wherein R is an alkyl, or cycloalkyl, an aralkyl, a haloalkyl, an alkoxyalkyl, a hydroxyalkyl, an N,N-dialkylaminoalkyl, an unsubstituted or halogen-, alkyl-, alkoxy- or hydroxy-substituted aryl, or an ammoniumalkyl; X is a group of the formula, STR2 wherein A is STR3 or an unsubstituted or halogen-substituted arylene, or a group of the formula, STR4 wherein R1 is hydrogen, an alkyl, phenyl, a hydroxyalkyl, or an alkoxyalkyl; Y is --CO--, --COO--, --CONR3 -- (where R3 is hydrogen or an alkyl), or --SO2 --; R2 is hydrogen, an alkyl, a cycloalkyl, an aralkyl, a haloalkyl, an alkyl- or aryl-substituted amino-alkyl, an unsubstituted or halogen-, alkyl-, alkoxy-, hydroxy-, amino- or alkylamino-substituted aryl, a group of the formula, STR5 (where R, R1 and Y are as defined above and R4 is a bivalent group), or a group of the formula, (where R5 is direct linkage or a bivalent group; Q+ is a substituted ammonium, a cycloammonium or a hydrazinium; and α- is an anion), Which is useful for optically brightening an organic polymer material.
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