- An efficient and scalable synthesis of Isodesmosine
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Isodesmosine is 1,2,3,5-tetrasubstituted pyridinium-based amino acid substituted with four lysine derivatives found in elastin which is the main component of elastic fiber. Elastin plays a vital role in providing stretchy properties to tissues and body organs. Isodesmsoine is a proven to be useful biomarker for elastin degradation during the progressing stage of chronic obstructive pulmonary disease (COPD) and related diseases. The present work reported an efficient and gram-scale approach for the synthesis of Isodesmosine, starting from readily available Boc-Asp-OtBu using mild reaction conditions.
- Ashish,Chaudhari, Vinod D.,Gupta, Aikan,Nihalani, Deepak,Pawar, Ganesh P.,Sharma, Yogesh
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-
- NOVEL HISTONE METHYLTRANSFERASE INHIBITORS
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The present invention relates to novel compounds of formula (I) as defined herein. The compounds are inhibitors of histone methyltransferases of the seven-beta-strand family, in particular of KMT9.
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- Chemical synthesis of disulfide surrogate peptides by using beta-carbon dimethyl modified diaminodiacids
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The replacement of disulfide bridges with metabolically stable isosteres is a promising strategy to improve the stability of disulfide-rich polypeptides towards reducing agents and isomerases. A diaminodiacid-based strategy is one of the most effective methods to construct disulfide bond mimics, but modified diaminodiacids have not been developed till now. Inspired by the fact that alkylation of disulfide bonds can regulate the activity of polypeptides, herein, we report the first example of thioether bridged diaminodiacids incorporating Cys Cβdimethyl modification, obtained by penicillamine (Pen)-based thiol alkylation. The utility of these new diaminodiacids was demonstrated by the synthesis of disulfide surrogates of oxytocin containing a short-span disulfide bond and of KIIIA with large-span disulfide bonds. This new type of synthetic bridge further extends the diaminodiacid toolbox to facilitate the study of the structure-activity relationship of disulfide-rich peptides.
- Bierer, Donald,Cui, Ji-Bin,Li, Yi-Ming,Shi, Jing,Wei, Xiao-Xiong,Zhao, Rui,Zhu, Huixia
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supporting information
p. 9021 - 9025
(2021/11/04)
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- Diaminodiacid bridge improves enzymatic and in vivo inhibitory activity of peptide CPI-1 against botulinum toxin serotype A
-
The replacement of the disulfide bridge of CPI-1, a peptide inhibitor of light chain of Botulinum toxin serotype A, with the thioether-containing and biscarba-containing diaminodiacid bridge leads to a significant decrease in the degradation by trypsin and increase in the detoxification activity in vivo, the addition of hydrophobic or positive amino acid at C-terminus of modified peptides further improves the inhibitory activity.
- Shen, Jintao,Liu, Jia,Yu, Shuo,Yu, Yunzhou,Huang, Chao,Xiong, Xianghua,Yue, Junjie,Dai, Qiuyun
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supporting information
p. 4049 - 4052
(2021/04/19)
-
- Improved enantioselective gram scale synthesis route to N-Fmoc-protected monofluoroethylglycine
-
Fluorine, as a substituent in amino acids, has found its way into peptide and protein engineering. The basis for the use of this valuable tool is the synthetic accessibility of various fluorinated amino acids as building blocks of peptides and proteins. In this context, we present a straightforward eight-step synthesis of N-Fmoc-L-monofluoroethylglycine (MfeGly) via homoserine (Hse) as intermediate and using various nucleophilic fluorination strategies.
- Leppkes, Jakob,Hohmann, Thomas,Koksch, Beate
-
-
- Stereoselective Synthesis of Protected l - Allo -Enduracididine and l -Enduracididine via Asymmetric Nitroaldol Reaction
-
The diastereoselecetive and scalable synthesis of cyclic guanidine-containing nonproteinoginic amino acids, enduracididines, has been achieved. Both diastereomers, l - allo -enduracididine and l -enduracididine, were prepared via catalyst-controlled asymmetric nitroaldol reaction with the aldehyde precursor derived from l -aspartic acid. The cyclic guanidine of di-Cbz-protected l - allo -enduracididine was fully protected with an allyl group to suppress nucleophilic side reactions. Introduced allyl group was efficiently removed via π-allylpalladium chemistry without attaching the Cbz group on the cyclic guanidine moiety.
- Doi, Takayuki,Ganesan, A.,Masuda, Yuichi,Ohsawa, Kosuke,Thomas, Carys,Tokunaga, Takuya,Zhao, Hongbin
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supporting information
p. 942 - 948
(2020/03/23)
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- BIHETEROCYCLIC COMPOUND
-
The present invention provides a compound of formula (1) and a pharmaceutical composition comprising the compound useful as a nerve regeneration promoter wherein R1-L- is R1—OC(O)—, or the like, R1 is hydrogen atom, optionally-substituted C1-6 alkyl group, optionally-substituted 3- to 8-membered cycloalkyl group, or the like, R2 is hydrogen atom or the like, Ring A is formula (2) or formula (3) wherein R3 is hydrogen atom, optionally-substituted C1-6 alkyl group, or the like, the part of X, Y, and Z is X═Y—Z, X—Y═Z, or X—Y—Z, X is nitrogen atom, NR4 (R4 is hydrogen atom, optionally-substituted C1-6 alkyl group, or the like), or the like, Y is carbon atom or the like, and Z is carbon atom, nitrogen atom or the like.
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Paragraph 1150-1152
(2019/02/01)
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- HYPERPOLARIZED AND DEUTERIUM EXCHANGED HYPERPOLARIZED13C AND 15N-LABELED XANTHINE, ARGININE, GLUTAMINE, AND UREA PROBES
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The present technology provides 13C- and 15N-labeled probes for imaging one or more mammalian cells using magnetic resonance. Thus, 13C- and 15N-labeled arginine (compound of formula I), xanthine (compounds of f
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-
Paragraph 0076; 0097
(2019/04/11)
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- Process for preparing deuterated desmosine and derivatives thereof
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There is provided a process for preparing a compound represented by the following general formula (1) or a salt thereof, which comprises exchanging one or more of an amino proton in a compound represented by the following general formula (2) or a salt thereof to deuterium, and after the exchanging, converting a deuterium-exchanged compound of the compound represented by the general formula (2) or a salt thereof into the compound represented by the general formula (1) or a salt thereof: wherein, in the general formula (1), one, or two or more of hydrogen atom may be substituted with their isotope; and in the general formula (2), each of R1 is independently hydrogen atom, tert-butyloxycarbonyl group or benzyloxycarbonyl group, and R2 is independently tert-butyl group, benzyl group, methyl group or ethyl group.
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Page/Page column 7; 11
(2019/05/18)
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- Hyperpolarized [6-13C,15N3]-Arginine as a Probe for in Vivo Arginase Activity
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Alterations in arginase enzyme expression are linked with various diseases and have been shown to support disease progression, thus motivating the development of an imaging probe for this enzymatic target. 13C-enriched arginine can be used as a
- Cho, Andrew,Keshari, Kayvan R.,Eskandari, Roozbeh,Granlund, Kristin L.
-
p. 665 - 673
(2019/06/18)
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- COMPLEX
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PROBLEM TO BE SOLVED: To provide a substance that can be used in a simple quantitative method for desmosines. SOLUTION: In the complex of the present invention, desmosine is bound to a protein directly or via a linking group at the side chain terminal of the 4-position of the pyridine ring of desmosine. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
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- Multigram-scale and column chromatography-free synthesis of L-azetidine-2-carboxylic acid for the synthesis of nicotianamine and its derivatives
-
Multigram-scale synthesis of L-azetidine-2-carboxylic acid from L-aspartic acid was achieved in 13 conventional synthetic steps, without the need for purification by silica-gel column chromatography and expensive reagents. Nicotianamine and its fluorescence-labeled derivatives could be obtained from this synthetic strategy.
- Takaishi, Tomohiro,Wakisaka, Kyosuke,Vavricka, Christopher J.,Kiyota, Hiromasa,Izumi, Minoru
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p. 2126 - 2134
(2019/04/04)
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- Synthesis of meta-Carboranyl-(S)-homocysteine Sulfoxide
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New (S)-homocysteine derivatives containing a meta-carborane fragment were synthesized. m-Carboranyl-(S)-homocysteine sulfoxide was obtained as a mixture of diastereoisomers. The reduction of the side-chain carboxy group of N-tert-butoxycarbonyl-(S)-aspartic acid α-tert-butyl ester with sodium tetrahydridoborate was not accompanied by racemization.
- Gruzdev,Ustinova,Levit,Ol’shevskaya,Krasnov
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p. 1579 - 1582
(2019/01/04)
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- Environmentally-friendly orthogonally protected diaminodiacid compound, and preparation method and application thereof
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The invention discloses an environmentally-friendly orthogonally protected diaminodiacid compound, and a preparation method and an application thereof. The structural formula of the environmentally-friendly orthogonally protected diaminodiacid compound is
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-
- Inhibitors of nicotinamide: N -methyltransferase designed to mimic the methylation reaction transition state
-
Nicotinamide N-methyltransferase (NNMT) is an enzyme that catalyses the methylation of nicotinamide to form N′-methylnicotinamide. Both NNMT and its methylated product have recently been linked to a variety of diseases, suggesting a role for the enzyme as a therapeutic target beyond its previously ascribed metabolic function in detoxification. We here describe the systematic development of NNMT inhibitors derived from the structures of the substrates involved in the methylation reaction. By covalently linking fragments of the NNMT substrates a diverse library of bisubstrate-like compounds was prepared. The ability of these compounds to inhibit NNMT was evaluated providing valuable insights into the structural tolerances of the enzyme active site. These studies led to the identification of new NNMT inhibitors that mimic the transition state of the methylation reaction and inhibit the enzyme with activity on par with established methyltransferase inhibitors.
- Van Haren, Matthijs J.,Taig, Rebecca,Kuppens, Jilles,Sastre Tora?o, Javier,Moret, Ed E.,Parsons, Richard B.,Sartini, Davide,Emanuelli, Monica,Martin, Nathaniel I.
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p. 6656 - 6667
(2017/08/16)
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- Synthesis of purpuroine A, nakirodin A and MDN-0104: The hidden puzzles and risk of error in their configurational assignments
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The unusual (R) configuration previously assigned (with seemingly undoubted evidence) to purpuroin A and nakirodin A was disproved by synthesis. The optical rotation and NMR data for structure assigned for salt-free nakirodin A were made available for the
- Wu, Wen-Ju,Wu, Yikang,Liu, Bo
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p. 1265 - 1274
(2017/02/10)
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- Synthesis of desmosine-d4: Improvement of isotopic purity by D-H exchange of amino groups
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Desmosine is a crosslinking pyridinium amino acid of elastin, which is a useful biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD) by LC–MS/MS analysis. We previously reported a synthesis of desmosine-d4, which is useful as an internal standard for quantitative LC–MS/MS analysis of desmosines, by deuterogenation of an alkyne group; however, the isotopic purity of the desmosine-d4was only ca. 50%. The present report describes a new synthesis of desmosine-d4that improves the isotopic purity to ca. 90% by exchanging the protons of the amino groups to deuterium using deuterogenation.
- Watanabe, Daisuke,Suzuki, Rina,Usuki, Toyonobu
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p. 1194 - 1197
(2017/03/02)
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- Facile synthesis of Fmoc-protected phosphonate pSer mimetic and its application in assembling a substrate peptide of 14-3-3 ζ
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Phosphatase-inert peptidomimetics containing phosphonate pSer analogue have been developed as valuable biological tools for probing and regulating pSer-dependent protein-protein interactions (PPIs) in cellular context. Herein, we report a facile and efficient synthesis route of Fmoc-protected phosphonate pSer mimetic and also present the application of this building block in the solid-phase synthesis of a phosphatase-resistant substrate peptide of 14-3-3 ζ, retaining 14-3-3 ζ binding efficacy similar to the parent pSer-containing peptide.
- Kang, Jie,Chen, Hong-Xue,Huang, Si-Qi,Zhang, Yun-Lai,Chang, Rong,Li, Fang-Yi,Li, Yan-Mei,Chen, Yong-Xiang
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p. 2551 - 2553
(2017/06/13)
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- Efficient synthesis of hydrocarbon-bridged diaminodiacids through nickel-catalyzed reductive cross-coupling
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Solid-phase incorporation of pre-prepared diaminodiacids has been established as an efficient strategy for the chemical synthesis of peptide disulfide bond mimics. Hydrocarbon-bridged diaminodiacids represent one important category of diaminodiacids but they remain difficult to synthesize. In the present work, we reported the use of newly-developed nickel catalyzed reductive cross-coupling reaction to efficiently synthesize diaminodiacids with hydrocarbon bridges. Through optimization of the reaction conditions, the yield of the hydrocarbon bridge formation reached about 50%, even when the reaction was scaled up to the gram level. Subsequently, using our recently developed Dmab/ivDde protecting group system, we obtained a new hydrocarbon-bridged diaminodiacid that are suitable for metal-free deprotection conditions. We demonstrated the utility of this Dmab/ivDde protected hydrocarbon-bridged diaminodiacid in the synthesis of a disulfide surrogate of oxytocin.
- Wang, Tao,Kong, Yi-Fu,Xu, Yang,Fan, Jian,Xu, Hua-Jian,Bierer, Donald,Wang, Jun,Shi, Jing,Li, Yi-Ming
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p. 3970 - 3973
(2017/09/26)
-
- Preparing phosphorylated serine phosphonic acid mimetics of the method (by machine translation)
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The invention relates to preparing phosphorylated serine phosphonic acid mimetics of the method, in particular, the method comprises: (1) the formula 1 as shown in the reduction reaction, in order to obtains the type 2 illustrated compound; (2) causes to state the type 2 as shown in performing the bromination reaction, in order to obtains the type 3 illustrated compound; (3) causes to state the type 3 a compound of the formula 4 compound shown in contact, in order to obtains the type 5 illustrated compound; (4) causes to state the type 5 as shown in the de-protecting group, in order to obtains the type (I) the compounds of formula, wherein R is hydrogen, benzyl, O-nitryl phenmethyl, coumarin or allyl, R1is benzyl, O-nitryl phenmethyl, coumarin or allyl. The method adopted by the raw materials are cheap, easy to obtain, the reaction route steps are less, the overall yield of the whole route in 20% or more, can be prepared to obtain high yield and high quality of the phosphorylated serine phosphonic acid mimetics. (by machine translation)
- -
-
Paragraph 0048; 0049; 0050
(2017/01/02)
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- Trifluoroselenomethionine: A New Unnatural Amino Acid
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Trifluoroselenomethionine (TFSeM), a new unnatural amino acid, was synthesized in seven steps from N-(tert-butoxycarbonyl)-l-aspartic acid tert-butyl ester. TFSeM shows enhanced methioninase-induced cytotoxicity, relative to selenomethionine (SeM), toward HCT-116 cells derived from human colon cancer. Mechanistic explanations for this enhanced activity are computationally and experimentally examined. Comparison of TFSeM and SeM by selenium EXAFS and DFT calculations showed them to be spectroscopically and structurally very similar. Nonetheless, when two different variants of the protein GB1 were expressed in an Escherichia coli methionine auxotroph cell line in the presence of TFSeM and methionine (Met) in a 9:1 molar ratio, it was found that, surprisingly, 85 % of the proteins contained SeM residues, even though no SeM had been added, thus implying loss of the trifluoromethyl group from TFSeM. The transformation of TFSeM into SeM is enzymatically catalyzed by E. coli extracts, but TFSeM is not a substrate of E. coli methionine adenosyltransferase.
- Block, Eric,Booker, Squire J.,Flores-Penalba, Sonia,George, Graham N.,Gundala, Sivaji,Landgraf, Bradley J.,Liu, Jun,Lodge, Stephene N.,Pushie, M. Jake,Rozovsky, Sharon,Vattekkatte, Abith,Yaghi, Rama,Zeng, Huawei
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p. 1738 - 1751
(2016/11/17)
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- [18F](2S,4S)-4-(3-Fluoropropyl)glutamine as a tumor imaging agent
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Although the growth and proliferation of most tumors is fueled by glucose, some tumors are more likely to metabolize glutamine. In particular, tumor cells with the upregulated c-Myc gene are generally reprogrammed to utilize glutamine. We have developed new 3-fluoropropyl analogs of glutamine, namely [18F](2S,4R)- and [18F](2S,4S)-4-(3-fluoropropyl)glutamine, 3 and 4, to be used as probes for studying glutamine metabolism in these tumor cells. Optically pure isomers labeled with 18F and 19F (2S,4S) and (2S,4R)-4-(3-fluoropropyl)glutamine were synthesized via different routes and isolated in high radiochemical purity (>95%). Cell uptake studies of both isomers showed that they were taken up efficiently by 9L tumor cells with a steady increase over a time frame of 120 min. At 120 min, their uptake was approximately two times higher than that of L-[3H]glutamine ([3H]Gln). These in vitro cell uptake studies suggested that the new probes are potential tumor imaging agents. Yet, the lower chemical yield of the precursor for 3, as well as the low radiochemical yield for 3, limits the availability of [18F](2S,4R)-4-(3-fluoropropyl)glutamine, 3. We, therefore, focused on [18F](2S,4S)-4-(3-fluoropropyl)glutamine, 4. The in vitro cell uptake studies suggested that the new probe, [18F](2S,4S)-4-(3-fluoropropyl)glutamine, 4, is most sensitive to the LAT transport system, followed by System N and ASC transporters. A dualisotope experiment using L-[3H]glutamine and the new probe showed that the uptake of [3H]Gln into 9L cells was highly associated with macromolecules (>90%), whereas the [18F](2S,4S)-4-(3-fluoropropyl)glutamine, 4, was not (18F](2S,4S)-4-(3-fluoropropyl)glutamine, 4, may be useful for testing tumors that may metabolize glutamine related amino acids.
- Wu, Zehui,Zha, Zhihao,Li, Genxun,Lieberman, Brian P.,Choi, Seok Rye,Ploessl, Karl,Kung, Hank F.
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p. 3852 - 3866
(2016/10/13)
-
- N-substituted sultam carboxylic acids as novel glycogen synthase activators
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Decreased glycogen synthesis and turnover is a common defect in type 2 diabetic patients. Activating glycogen synthase, the enzyme that catalyses the transfer of glucose from UDP-glucose to a glycogen polymer chain, could be a potential therapeutic target for the treatment of diabetes. We discovered a series of N-substituted sultam carboxylic acids as potent glycogen synthase activators. Treatment of human skeletal muscle cells with these compounds resulted in an increase in glycogen synthesis. Compound 4 displayed good oral bioavailability and therefore may be a useful tool molecule to study GS as a potential anti-diabetic target. The Royal Society of Chemistry 2013.
- Qian, Yimin,Bolin, David R.,Conde-Knape, Karin,Gillespie, Paul,Hayden, Stuart,Huang, Kuo-Sen,Liu, Mei,Olivier, Andree R.,Ren, Yonglin,Sergi, Joseph,Xiang, Qing,Yi, Lin,Yun, Weiya,Zhang, Xiaolei
-
p. 833 - 838
(2013/08/26)
-
- Novel thiol- and thioether-containing amino acids: Cystathionine and homocysteine families
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Natural l-homocysteine and l,l-cystathionine, along with a series of unnatural analogues, have been prepared from l-aspartic and l-glutamic acid. Manipulation of the protected derivatives provided ω-iodoamino acids, which were used in thioalkylation react
- Longobardo, Luigi,Cecere, Nunzia,DellaGreca, Marina,De Paola, Ivan
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p. 443 - 448
(2013/07/27)
-
- Synthesis and evaluation of tripeptidic plasmin inhibitors with nitrile as warhead
-
Plasmin is best known as the key molecule in the fibrinolytic system, which is critical for clot lysis and can initiate matrix metalloproteinase (MMP) activation cascade. Along with MMP, plasmin is suggested to be involved in physiological processes that are linked to the risk of carcinoma formation. Plasmin inhibitors could be perceived as a promising new principle in the treatment of diseases triggered by plasmin. On the basis of the peptidic sequence derived from the synthetic plasmin substrate, a series of peptidic plasmin inhibitors possessing nitrile as warhead were prepared and evaluated for their inhibitory activities against plasmin and other serine proteases, plasma kallikrein and urokinase. The most potent peptidic inhibitors with the nitrile warhead exhibit the potency toward plasmin (IC50=7.7-11μM) and are characterized by their selectivity profile against plasma kallikrein and urokinase. The results and molecular modeling of the peptidic inhibitor complexed with plasmin reveal that the P2 residue makes favorable contacts with the open binding pocket comprising the S2 and S3 subsites of plasmin.
- Teno, Naoki,Otsubo, Tadamune,Gohda, Keigo,Wanaka, Keiko,Sueda, Takuya,Ikeda, Kiyoshi,Hijikata-Okunomiya, Akiko,Tsuda, Yuko
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p. 620 - 625
(2013/01/13)
-
- SINGLE DIASTEREOMERS OF 4-FLUOROGLUTAMINE AND METHODS FO THEIR PREPARATION AND USE
-
The present invention is directed single diasteromers of 4-fluoroglutamine having a diastereomeric excess of at least 80%. Methods of preparing the single diastereomers are also described, as well as methods of using the single diastereomers of radiolabeled 4-fluoroglutamine as imaging agent is also described.
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- Fluoro-labeled homo-glutamate derivatives and precursors thereof
-
This invention relates to homoglutamic acid derivatives suitable for labeling or already labeled with 18F or 19F, methods of preparing such compounds, compositions comprising such compounds, kits comprising such compounds or compositions and uses of such compounds, compositions or kits for diagnostic imaging.
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Page/Page column 26-27
(2011/06/10)
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- HOMOGLUTAMIC ACID DERIVATIVES
-
This invention relates to homoglutamic acid derivatives suitable for labeling or already labeled with 18F or 19F, methods of preparing such compounds, compositions comprising such compounds, kits comprising such compounds or composit
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Page/Page column 53
(2011/06/16)
-
- Synthesis of optically pure 4-fluoro-glutamines as potential metabolic imaging agents for tumors
-
A versatile synthetic route to prepare all four stereoisomeric 4-fluoro-glutamines was developed by exploiting a Passerini three-component reaction. The skeleton of 4-substituted glutamine derivatives was efficiently constructed. Subsequent four-step reactions, highlighted by a "neutralized" TASF fluorination, provided the desired products with high yields and excellent optical purity. The optically pure fluorine-18 labeled 4-fluoroglutamines were also successfully prepared using either a 18-crown-6/KHCO3 or K[222]/K2CO3 catalysis system. Preliminary cell uptake and inhibition studies using the 9L tumor cells ana SF188BC1-XL tumor cells (a glutamine addicted tumor derived from glioblastoma) provided strong evidence for their potential application in conjunction with positron emission tomography (PET) for in vivo imaging of tumors, which use glutamine as an alternative energy source.
- Qu, Wenchao,Zha, Zhihao,Ploessl, Karl,Lieberman, Brian P.,Zhu, Lin,Wise, David R.,Thompson, Craig B.,Kung, Hank F.
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supporting information; experimental part
p. 1122 - 1133
(2011/04/16)
-
- PYRROLO [2, 3-D] PYRIMIDINES AS INHIBITORS OF HSP90
-
The invention provides a compound compound which is (a) a pyrrolopyrimidine derivative of formula (I) or a tautomer thereof, or (b) a pharmaceutically acceptable salt, N-oxide, hydrate or solvate thereof: wherein R1, R2, R3/sup
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Page/Page column 48-49
(2010/04/30)
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- Crystal structure analysis and reactivity of N-alkyl- and N-acyldioxathiazinanes
-
Cyclic sulfamidates have served as reactive electrophiles for the synthesis of various products, including alkaloids, substituted amines, amino acids and lactams. N-Acyl dioxathiazinanes exhibit enhanced reactivity relative their unsubstituted and N-alkyl
- Galaud, Fabrice,Blankenship, John W.,Lubell, William D.
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experimental part
p. 1121 - 1131
(2009/06/28)
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- Access to any site-directed isotopomer of methionine, selenomethionine, cysteine, and selenocysteine - Use of simple, efficient modular synthetic reaction schemes for isotope incorporation
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Simple modular reaction schemes that allow access to any isotopomer of protected serine and homoserine have been worked out. These systems could be simply converted into cysteine, selenocysteine, homocysteine, homoselenocysteine, the essential amino acid methionine, and selenomethionine by Mitsunobu chemistry. These sulfur- and selenium-containing amino acids fulfil many essential roles in the living organism. In addition, homoserine could be converted in a few steps into optically active L-vinylglycine. As well as the stable isotopes 13C, 15N, 17O, and 18O, the radioactive isotopes of sulfur, selenium and carbon can also be easily introduced in a site-directed fashion. In view of the wide scope of the Mitsunobu reaction, we feel that many more important systems with the carbon skeleton of serine and homoserine should be preparable through this basic chemistry in any site-directed isotopically labeled form. Wiley-VCH Verlag GmbH & Co, KGaA, 69451 Weinheim, Germany, 2004.
- Siebum, Arjan H. G.,Woo, Wei Sein,Raap, Jan,Lugtenburg, Johan
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p. 2905 - 2913
(2007/10/03)
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- Highly efficient chiral-pool synthesis of (2S,4R)-4-hydroxyornithine
-
(Figure Presented) A concise synthesis of the amino acid (2S,4R)-4-hydroxyornithine is described. Starting from diprotected L-aspartic acid, the scaffold of the target compound is constructed in a three-step approach: an efficient α-nitroketone formation
- Rudolph, Joachim,Hannig, Frithjof,Theis, Heidi,Wischnat, Ralf
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p. 3153 - 3155
(2007/10/03)
-
- α-Functionalized phosphonylphosphinates: Synthesis and evaluation as transcarbamoylase inhibitors
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Diverse α-methyl-substituted phosphonylphosphinates (P-C-P-C-X) are accessible from a protected, pentafluorophenylsulfonated phosphonylphosphinate via nucleophilic displacement. The utility of this route is demonstrated with several nitrogen nucleophiles. The resulting amine and amino acid phosphonylphosphinate derivatives were evaluated as inhibitors of Streptococcus faecalis ornithine transcarbamoylase (OTC). Compared with the structurally related phosphonoacetyl-L-ornithine (L-PALO), a known inhibitor of OTCs from various sources, the phosphonylphosphinates are surprisingly poor inhibitors, binding several orders of magnitude less tightly to the enzyme. These results suggest that the tetrahedral intermediate formed in the normal transcarbamoylase reaction is poorly mimicked by a tetrahedral and anionic phosphonate, either because of directly unfavorable interactions with a hydrogen-bond acceptor within the active site or because transition-state analogues are unable to induce the protein conformation changes that normally accompany reaction.
- Flohr, Alexander,Aemissegger, Andreas,Hilvert, Donald
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p. 2633 - 2640
(2007/10/03)
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- Nucleic acid-binding oligomers possessing C-branching for therapy and diagnostics
-
The invention relates to nucleic acid-binding oligomers possessing C-branching of the general formula (I) STR1 and to the corresponding monomers, whose radicals have the meaning given in the description, and to their use as medicaments or diagnostic aids.
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-
- A new efficient synthesis of nicotianamine and 2′-deoxymugineic acid
-
Nicotianamine and 2′-deoxymugineic acid, phytosiderophores, have been efficiently synthesized, which will be suitable for large scale production of these plant physiologically important compounds. The synthetic method for 2′,3″-dideoxy-3″-oxomugineic acid was also investigated.
- Shioiri, Takayuki,Irako, Naoko,Sakakibara, Sachiko,Matsuura, Fumiyoshi,Hamada, Yasumasa
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p. 519 - 530
(2007/10/03)
-
- Synthesis and structure-activity relationships of a novel antifungal agent, azoxybacilin
-
A new antifungal substance, azoxybacilin (an unusual amino acid with an azoxy moiety) and its derivatives have been synthesized from Boc-L-Asp-O(t)Bu utilizing the Moss procedure for the preparation of the azoxy moiety. The ester derivative, Ro 09-1824, showed more potent antifungal activity and a broader antifungal spectrum than azoxybacilin did.
- Ohwada,Umeda,Ontsuka,Aoki,Shimma
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p. 1703 - 1705
(2007/10/02)
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- The Improved Synthesis of Boc-Abu(PO3Me2)-OH and its Use for the Facile Synthesis of Glu-Abu(P)-Leu
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The improved synthesis of Boc-L-Abu(PO3Me2)-OH from Boc-Asp-OBut in 42percent overall yield is described.This derivative was prepared in seven steps and involved initial sodium borohydride reduction of the isobutoxycarbonyl mixed anhydride of Boc-Asp-OBut and subsequent 2,2,6,6-tetramethylpiperidine-1-oxyl-catalysed sodium hypochlorite oxidation of the alcohol.The resultant aldehyde was phosphonylated by reflux with dimethyl trimethylsilyl phosphite and the trimethylsilyl group was then cleaved in situ by aqueous hydrolysis.The 4-hydroxy 4-dimethylphosphono derivative was converted into the Abu(PO3Me2) residue by reaction with thiocarbonyldiimidazole followed by radical deoxygenation of the thiocarbonylimidazolide with tributyltin hydride.The Boc and t-butyl groups were cleaved from Boc-Abu(PO3Me2)-OBut with trifluoroacetic acid and the Boc group was reintroduced to H-Abu(PO3Me2)-OH by using di-t-butyl dicarbonate to give Boc-Abu(PO3Me2)-OH as a clear oil.The optical purity of the Abu(PO3Me2) residue was established to be greater than 99.5percent of the L-isomer by h.p.l.c. analysis of its L-Leu dipeptide.The protected derivative Boc-Abu(PO3Me2)-OH was used in the Boc mode of peptide synthesis for the preparation of Boc-Glu(OBzl)-Abu(PO3Me2)-Leu-OBzl in high yield, 40percent CF3CO2H/CH2Cl2 being used for cleavage of the Boc group from intermediate peptides.The tripeptide was deprotected to H-Glu-Abu(P)-Leu-OH by a two-step procedure which involved initial hydrogenolytic cleavage of the benzyl groups in 50percent CF3CO2H/CH3CO2H followed by cleavage of the methyl phosphate groups with either (A) 30percent bromotrimethylsilane in acetonitrile, or (B) 1 M bromotrimethylsilane/1 M thioanisole in trifluoroacetic acid; complete cleavage of the methyl groups was effected after 40 min and 12 h, respectively.In addition, the dipeptide Boc-Leu-Abu(PO3Me2)-OBut was prepared from Boc-Abu(PO3Me2)-OBut in high yield and was readilly deprotected by acidolytic cleavage of the t-butyl groups with trifluoroacetic acid followed by silylitic cleavage of the methyl phosphonate groups with 30percent bromotrimethylsilane in acetonitrile, H-Leu-Abu(P)-OH being obtained in high yield.
- Tong, Glenn,Perich, John W.,Johns, R. B.
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p. 1225 - 1240
(2007/10/02)
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- Synthesis of Leu-Abu(P) and Glu-Abu( P)-Leu. Isosteres of ser(P)-peptides
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Boc-Asp-O1-Bu was efficiently converted to Boc-Abu(PO3Me2)-O1-Bu in five steps then to Boc-Abu(PO3Me2)OH in two steps. Both the protected amino acids were used in the syntheses of Boc-Leu-A
- Tong,Perich,Johns
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p. 3759 - 3762
(2007/10/02)
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