- N-transfer reagent and method for preparing the same and its application
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Provided are a novel N-transfer reagent and a method for preparing the same and its application. The N-transfer reagent is represented by the following Formula (I): The various novel N-transfer reagents of the present invention can be quickly prepared by employing different nitrobenzene precursors. The N-transfer reagents can directly convert a variety of amino compounds into diazo compounds under mild conditions. Particularly, the N-transfer reagents can facilitate the synthesis of the diazo compounds. The application of synthesizing diazo compounds of the present invention can greatly decrease the difficulty in operation, increase the safety during experiments, reduce the cost of production and the environmental pollution, and enhance the industrial value of diazo compounds.
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Page/Page column 22-23; 47-50; 51-54
(2021/06/25)
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- 4'-THIO-NUCLEOTIDE AND -NUCLEOSIDE PRODRUGS FOR THE TREATMENT OF CANCER
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The present disclosure is concerned with 4'-thio nucleotide and nucleoside compounds for the treatment of various cancers such as, for example, sarcomas, carcinomas, hematological cancers, solid tumors, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, bladder cancer, thyroid cancer, testicular cancer, pancreatic cancer, endometrial cancer, melanomas, gliomas, leukemias, lymphomas, chronic myeloproliferative disorders, myelodysplastic syndromes, myeloproliferative neoplasms, and plasma cell neoplasms (myelomas). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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Paragraph 00423
(2019/11/12)
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- Identification of a 4-fluorobenzyl L-valinate amide benzoxaborole (AN11736) as a potential development candidate for the treatment of Animal African Trypanosomiasis (AAT)
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Novel L-valinate amide benzoxaboroles and analogues were designed and synthesized for a structure-activity-relationship (SAR) investigation to optimize the growth inhibitory activity against Trypanosoma congolense (T. congolense) and Trypanosoma vivax (T. vivax) parasites. The study identified 4-fluorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate (5, AN11736), which showed IC50 values of 0.15 nM against T. congolense and 1.3 nM against T. vivax, and demonstrated 100% efficacy with a single dose of 10 mg/kg against both T. congolense and T. vivax in mouse models of infection (IP dosing) and in the target animal, cattle, dosed intramuscularly. AN11736 has been advanced to early development studies.
- Akama, Tsutomu,Zhang, Yong-Kang,Freund, Yvonne R.,Berry, Pamela,Lee, Joanne,Easom, Eric E.,Jacobs, Robert T.,Plattner, Jacob J.,Witty, Michael J.,Peter, Rosemary,Rowan, Tim G.,Gillingwater, Kirsten,Brun, Reto,Nare, Bakela,Mercer, Luke,Xu, Musheng,Wang, Jiangong,Liang, Hao
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- Efficient near infrared fluorescence detection of elastase enzyme using peptide-bound unsymmetrical squaraine dye
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Extended wavelength analyte-responsive fluorescent probes are highly desired for the imaging applications owing to their deep tissue penetration, and minimum interference from autofluorescence by biomolecules. Near infra-red (NIR) sensitive and self-quenching fluorescent probe based on the dye-peptide conjugate (SQ 1 PC) was designed and synthesized by facile and efficient one-pot synthetic route for the detection of Elastase activity. In the phosphate buffer solution, there was an efficient quenching of fluorescence of SQ 1 PC (86%) assisted by pronounced dye-dye interaction due to H-aggregate formation. Efficient and fast recovery of this quenched fluorescence of SQ 1 PC (> 50% in 30 s) was observed on hydrolysis of this peptide-dye conjugate by elastase enzyme. Presently designed NIR sensitive self-quenching substrate offers the potential application for the detection of diseases related to proteases by efficient and fast detection of their activities.
- Saikiran, Maryala,Sato, Daisuke,Pandey, Shyam S.,Hayase, Shuzi,Kato, Tamaki
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supporting information
p. 4024 - 4029
(2017/08/23)
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- Discovery of 2'-α-C-Methyl-2'-β-C-fluorouridine Phosphoramidate Prodrugs as Inhibitors of Hepatitis C Virus
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2′-α-C-Methyl-2′-β-C-fluorouridine and its phosphoramidate prodrugs were synthesized and evaluated for their inhibitory activity against HCV. The structure?activity relationship analysis of the phosphoramidate moiety found that 17m, 17q, and 17r exhibit potent activities against HCV, with EC50 values of 1.82 ± 0.19, 0.88 ± 0.12, and 2.24 ± 0.22 μM, respectively. The docking study revealed that the recognition of the 2′-β-F by Arg158, 3′-OH by N291, and the Watson?Crick pairing with the template allowed 23 to form the in-line conformation necessary for its incorporation into the viral RNA chain.
- Zeng, Debin,Zhang, Rui,Nie, Quandeng,Cao, Lin,Shang, Luqing,Yin, Zheng
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supporting information
p. 1197 - 1201
(2016/12/18)
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- Chiral recognition of carboxylates by a static library of thiourea receptors with amino acid arms
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Chiral recognition is based on a large network of very subtle interactions whose outcome is difficult to predict. A combinatorial approach is therefore the most suitable to search for the most efficient receptor and obtain a structure-enantioselectivity correlation. We synthesized a set of 12 receptors constructed with 1,9-diaminoantracene and α-amino acid esters, linked via thiourea groups. The association constants and enantioselectivities for the complexes with mandelate and N-acetylphenylalanine were determined by competitive NMR titrations. Association constants quite regularly depend on the substituents in the receptor structure, but the distribution of enantioselectivities across the library could not easily be rationalized.
- Ulatowski, Filip,Jurczak, Janusz
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p. 4235 - 4243
(2015/05/13)
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- 4'-Difluoromethyl Substituted Nucleoside Derivatives as Inhibitors of Influenza RNA Replication
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The application discloses nucleoside derivatives of Formula I as inhibitors of Influenza RNA replication. In particular, the application discloses the use of purine and pyrimidine nucleoside derivatives of Formula I as inhibitors of Influenza RNA replication and pharmaceutical compositions containing such compounds.
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- Novel Isobaric Tandem Mass Tags for Quantitative Proteomics and Peptidomics
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Compositions and methods of tagging peptides and other molecules using novel isobaric tandem mass tagging reagents, including novel N,N-dimethylated amino acid 8-plex and 16-plex isobaric tandem mass tagging reagents. The tagging reagents comprise: a) a reporter group having at least one atom that is optionally isotopically labeled; b) a balancing group, also having at least one atom that is optionally isotopically labeled, and c) an amine reactive group. The tagging reagents disclosed herein serve as attractive alternatives for isobaric tag for relative and absolute quantitation (iTRAQ) and tandem mass tags (TMTs) due to their synthetic simplicity, labeling efficiency and improved fragmentation efficiency.
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Paragraph 0199
(2013/04/10)
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- Esterification of unprotected a-Amino acids in ionic liquids as the reaction media
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Ionic liquid 1,3-dimethylimidazolium methanesulfonate was used to prepare a-amino acids benzylic esters from unprotected amino acids and benzyl chloride. Esterification of several amino acids was achieved with satisfactory yields: by-products can be removed by a simple work-up procedure to afford the pure product. The described method is simple, mild, rapid and save.
- Biondini, Daniele,Brinchi, Lucia,Germani, Raimondo,Goracci, Laura,Savelli, Gianfranco
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experimental part
p. 39 - 44
(2010/08/22)
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- A class of novel carboline intercalators: Their synthesis, in vitro anti-proliferation, in vivo anti-tumor action, and 3D QSAR analysis
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Based on DOCK scores 18 N-(3-benzyloxycarbonylcarboline-1-yl)ethylamino acid benzylesters (6a-r) were synthesized as anti-tumor agents. Their IC 50 values against five human carcinoma cell lines ranged from 11.1 μM to more than 100 μM. The in vivo assay identified five derivatives of them had no anti-tumor action, the anti-tumor activity of nine derivatives of them equaled that of cytarabine, and the anti-tumor activity of three derivatives of them was higher than that of cytarabine. The UV and fluorescence spectra, as well as the relative viscosity and melting temperature measurements of calf thymus DNA (CT DNA) with and without the representative compound suggested that DNA intercalation could be their action mechanism. The 3D QSAR analysis of N-(3-benzyloxycarbonylcarboline-1-yl)ethylamino acid benzylesters (6a-r) revealed that their in vivo anti-tumor activity significantly depends on the molecular electrostatic and steric fields of the side chain of the amino acid residue.
- Wu, Jianhui,Li, Chunyu,Zhao, Ming,Wang, Wenjing,Wang, Yuji,Peng, Shiqi
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experimental part
p. 6220 - 6229
(2010/10/04)
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- Synthesis of four lysine-linked cereulide analogues showing ionophoric activity towards potassium cations as lead compounds for emetic toxin-detection by immunoassays
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An improved total synthesis of the emetic toxin cereulide and the preparation of four lysine-linked cereulide analogues is described. The cereulide analogues are prepared by replacing one of the amino acid residues in cereulide with lysine. The cereulide analogues demonstrate ionophoric activity towards alkali metal ions and inorganic ammonium ions, and are currently being used to develop an enzyme-linked immunosorbent assay for cereulide. Georg Thieme Verlag Stuttgart.
- Makarasen, Arthit,Nishikawa, Toshio,Isobe, Minoru
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experimental part
p. 2184 - 2204
(2009/12/29)
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- 6-Hydrazinopurine 2′-methyl ribonucleosides and their 5′-monophosphate prodrugs as potent hepatitis C virus inhibitors
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A series of 6-hydrazinopurine 2′-methyl ribonucleosides was synthesized and tested for its inhibitory activity against the hepatitis C virus (HCV). The lack of antiviral activity of these nucleosides was associated with a poor affinity for adenosine kinase, which prompted us to synthesize several of their 5′-monophosphate prodrugs. Some of these prodrugs exhibited more than 1000-fold improvement in anti-HCV activity when compared to their parent nucleosides (EC50 of 24 nM vs 92 μM for the parent).
- Gunic, Esmir,Chow, Suetying,Rong, Frank,Ramasamy, Kanda,Raney, Anneke,Yunzhi Li, David,Huang, Jingfan,Hamatake, Robert K.,Hong, Zhi,Girardet, Jean-Luc
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p. 2456 - 2458
(2008/02/03)
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- Total synthesis and biological evaluation of tamandarin B analogues
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(Chemical Equation Presented) Tamandarins A and B are a class of marine natural cyclodepsipeptides with structures and biological activities closely related to those of the didemnins. The easier synthetic access to tamandarins accelerates the preparation of new macrocyclic derivatives of this family of antitumor, antiviral, and immunosuppressive compounds. The optimization of the previously reported synthetic route to tamandarins by changing the macrolactamization site from Nst1 and Thr6 to Pro 4 and N,O-Me2Tyr5 residues led to a significant improvement in the reaction yield. Using this new synthetic approach, four new macrocyclic analogues of tamandarin B were prepared and evaluated for anticancer activity. These results provide further insight into the structure-activity relationship of the tamandarins and didemnins.
- Adrio, Javier,Cuevas, Carmen,Manzanares, Ignacio,Joullie, Madeleine M.
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p. 5129 - 5138
(2008/02/07)
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- Carboline-3-carboxylic acid modified related sequences of Ala-Arg-Pro-Ala-Lys, their synthesis and use as thromobolytic agent
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The present invention relates to the protected intermediates and the deprotected products of P6A, related to the protected pseudopeptides introducing the protected intermediateds of P6A to 3S-(2-Boc)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid and the deprotected pseudopeptides, related to the protected pseudopeptides introducing the protected intermediateds of P6A to 3S-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid benzyl ester, related to the methods for their preparation, and related to their use as the thrombolytic agents.
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Page/Page column 10-11
(2010/02/11)
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- N-bis-silylation of α-amino acids: "benzostabases" as amino protecting group
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N-Bis-trimethylsilylation of α-amino acids using the powerful trimethylsilyl triflate reagent is difficult, and is rendered impossible in the case of bulky side-chains (valine). However, favorable entropy changes resulting from a cyclization reaction allow the formation of "benzostabase" N-diprotections regardless of the side-chain bulk.
- Cavelier-Frontin, Florine,Jacquier, Robert,Paladino, Joseph,Verducci, Jean
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p. 9807 - 9822
(2007/10/02)
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