- Thiyl radical-mediated cleavage of allylic C-N bonds: Scope, limitations, and theoretical support to the mechanism
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Thiols mediate the radical isomerization of allylic amines into enamines. The reaction results in the cleavage of the allylic C-N bond, after treatment with aqueous HCI. The mechanism involves the abstraction of an allylic hydrogen α to nitrogen by thiyl
- Escoubet, Stephanie,Gastaldi, Stephane,Timokhin, Vitaliy I.,Bertrand, Michele P.,Siri, Didier
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- Urethanes synthesis from oxamic acids under electrochemical conditions
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Urethane synthesis via oxidative decarboxylation of oxamic acids under mild electrochemical conditions is reported. This simple phosgene-free route to urethanes involves an in situ generation of isocyanates by anodic oxidation of oxamic acids in an alcoholic medium. The reaction is applicable to a wide range of oxamic acids, including chiral ones, and alcohols furnishing the desired urethanes in a one-pot process without the use of a chemical oxidant.
- Ogbu, Ikechukwu Martin,Lusseau, Jonathan,Kurtay, Gülbin,Robert, Frédéric,Landais, Yannick
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p. 12226 - 12229
(2020/10/26)
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- Ynamide Smiles Rearrangement Triggered by Visible-Light-Mediated Regioselective Ketyl-Ynamide Coupling: Rapid Access to Functionalized Indoles and Isoquinolines
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In the past decades, significant advances have been made on radical Smiles rearrangement. However, the eventually formed radical intermediates in these reactions are limited to the amidyl radical, except for the few examples initiated by a N-centered radical. Here, a novel and practical radical Smiles rearrangement triggered by photoredox-catalyzed regioselective ketyl-ynamide coupling is reported, which represents the first radical Smiles rearrangement of ynamides. This method enables facile access to a variety of valuable 2-benzhydrylindoles with broad substrate scope in generally good yields under mild reaction conditions. In addition, this chemistry can also be extended to the divergent synthesis of versatile 3-benzhydrylisoquinolines through a similar ketyl-ynamide coupling and radical Smiles rearrangement, followed by dehydrogenative oxidation. Moreover, such an ynamide Smiles rearrangement initiated by intermolecular photoredox catalysis via addition of external radical sources is also achieved. By control experiments, the reaction was shown to proceed via key ketyl radical and α-imino carbon radical intermediates.
- Chen, Yang-Bo,Sun, Zhou,Wang, Ze-Shu,Ye, Long-Wu,Zhang, Hao-Wen,Zhu, Chunyin
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supporting information
p. 3636 - 3644
(2020/03/06)
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- Easy Access to 2,4-Disubstituted Cyclopentenones by a Gold(III)-Catalyzed A3-Coupling/Cyclization Cascade
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An efficient and convenient synthesis of 2,4-disubstituted cyclopentenones has been achieved through a Au(III)-catalyzed isomerization-A3-coupling/cyclization cascade. A possible mechanism involving an initial Au(III)-catalyzed isomerization, A3-type coupling, and cyclization via an enol intermediate is postulated.
- Hu, Xiwen,Li, Jian,Liu, Li,Xu, Yue,Zhu, Shangrong
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supporting information
p. 9478 - 9483
(2020/12/21)
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- Synthesis of sulfamoylbenzamide derivatives as HBV capsid assembly effector
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The synthesis of novel series of sulfamoylbenzamides as HBV capsid assembly effector is reported. The structure was divided into five parts which were independently modified as part of our lead optimization. All synthesized compounds were evaluated for their anti-HBV activity and toxicity in human hepatocytes, lymphocytes and other cells. Additionally, we assessed their effect on HBV cccDNA formation in an HBeAg reporter cell-based assay. Among the 27 compounds reported, several analogs exhibited submicromolar activities and significant reduction of HBeAg secretion. Selected compounds were studied under negative-stain electron microscopy for their ability to disrupt the HBV capsid formation. Structures were modeled into a binding site recently identified in the HBV capsid protein for similar molecules to rationalize the structure-activity relationships for this family of compounds.
- Sari, Ozkan,Boucle, Sebastien,Cox, Bryan D.,Ozturk, Tugba,Russell, Olivia Ollinger,Bassit, Leda,Amblard, Franck,Schinazi, Raymond F.
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p. 407 - 421
(2017/07/10)
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- Hofmann Rearrangement of Carboxamides Mediated by N-Bromoacetamide
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An efficient, one-pot procedure for the Hofmann rearrangement of aromatic and aliphatic amides has been developed. Methyl and benzyl carbamates are produced with N-bromoacetamide in the presence of lithium hydroxide or lithium methoxide, in high yields. β-Phenylamino amides gave five-membered cyclic ureas stereospecifically. Side products of aryl or benzyl bromination were minimized. This procedure offers an easy access to various protected amines or diamines, which represent important synthetic precursors.
- Jevti?, Ivana I.,Do?en-Mi?ovi?, Ljiljana,Ivanovi?, Evica R.,Ivanovi?, Milovan D.
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p. 1550 - 1560
(2016/06/01)
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- Evaluation of ethyl: N -(2-phenethyl) carbamate analogues as biofilm inhibitors of methicillin resistant Staphylococcus aureus
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A small molecule library consisting of 45 compounds was synthesized based on the bacterial metabolite ethyl N-(2-phenethyl) carbamate. Screening of the compounds revealed a potent analogue capabale of inhibiting several strains of Methicillin Resistant S. aureus biofilms with low to moderate micromolar IC50 values.
- Stephens, Matthew D.,Yodsanit, Nisakorn,Melander, Christian
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p. 6853 - 6856
(2016/07/21)
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- Efficient synthesis of methyl carbamate via Hofmann rearrangement in the presence of TsNBr2
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An efficient method has been developed for the synthesis of carbamates from the corresponding amides via the Hofmann rearrangement using N,N-dibromo-p-toluenesulfonamide (TsNBr2) in the presence of DBU in methanol. The reaction goes into completion in 10-20 min at 65 °C to produce the corresponding carbamate in excellent yield.
- Borah, Arun Jyoti,Phukan, Prodeep
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experimental part
p. 3035 - 3037
(2012/07/27)
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- Hypervalent iodine catalyzed hofmann rearrangement of carboxamides using oxone as terminal oxidant
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Hofmann rearrangement of carboxamides to carbamates using Oxone as an oxidant can be efficiently catalyzed by iodobenzene. This reaction involves hypervalent iodine species generated in situ from catalytic amount of PhI and Oxone in the presence of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) in aqueous methanol solutions. Under these conditions, Hofmann rearrangement of various carboxamides affords corresponding carbamates in high yields.
- Yoshimura, Akira,Middleton, Kyle R.,Luedtke, Matthew W.,Zhu, Chenjie,Zhdankin, Viktor V.
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p. 11399 - 11404
(2013/02/23)
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- Highly efficient synthesis of ureas and carbamates from amides by iodosylbenzene-induced hofmann rearrangement
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A simple and efficient method for the synthesis of 1,3-disubstituted ureas and carbamates from amides by using iodosylbenzene as the oxidant is described. Symmetric and asymmetric ureas and carbamates can be prepared by this procedure in up to 98 % yield. Ureidopeptides can also be prepared in good yield by this method. A simple and efficient method for the synthesis of 1,3-disubstituted ureas and carbamates from amides by using iodosylbenzene as the oxidant is described. By using this method, heterocyclic products can be easily obtained in excellent yield. Ureidopeptides can also be prepared in good yield by this procedure. Copyright
- Liu, Peng,Wang, Zhiming,Hu, Xianming
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experimental part
p. 1994 - 2000
(2012/05/05)
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- Activation of electrophilicity of stable Y-delocalized carbamate cations in intramolecular aromatic substitution reaction: Evidence for formation of diprotonated carbamates leading to generation of isocyanates
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Although cations with three heteroatoms, such as monoprotonated guanidine and urea, are stabilized by Y-shaped conjugation and such Y-conjugated cations are sufficiently basic to be further protonated (or protosolvated) to dications in strongly acid media, only O-monoprotonated species have been detected in the case of carbamates even in magic acid. We found that the trifluoromethanesulfonic acid-catalyzed cyclization of arylethylcarbamates proceeds to afford dihydroisoquinolones in high yield. In strong acids, methyl carbamates are fully O-monoprotonated, and these monocations do not undergo cyclization even under heating. But, as the acidity of the reaction medium is further increased, the cyclization reaction of methyl phenethylcarbamates starts to proceed as a first-order reaction, with a linear relationship between rate and acidity. The sign and magnitude of the entropy of activation ΔS ? were found to be similar to those of other AAc1 reactions. These results strongly support the idea that further protonation of the O-protonated carbamates is involved in the cyclization, but the concentration of the dications is very low and suggests that the rate-determining step is dissociation of methanol from the diprotonated carbamate to generate protonated isocyanate, which reacts with the aromatic ring. Therefore, O-protonated carbamates are weak bases in sharp contrast to other Y-shaped monocations.
- Kurouchi, Hiroaki,Kawamoto, Kyoko,Sugimoto, Hiromichi,Nakamura, Satoshi,Otani, Yuko,Ohwada, Tomohiko
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p. 9313 - 9328,16
(2012/12/11)
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- Catalytic enantioselective tert-aminocyclization by asymmetric binary acid catalysis (ABC): Stereospecific 1,5-hydrogen transfer
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Selective H transfer by ABC: A new asymmetric binary acid catalyst was developed to promote 1,5-H transfer specifically and stereoselectively in tert-aminocyclization reactions with excellent activity, high enantioselectivity, and broad substrate scope. The H atom (in red) was proven to transfer through a stereospecific suprafacial pathway (see scheme).
- Chen, Liujuan,Zhang, Long,Lv, Jian,Cheng, Jin-Pei,Luo, Sanzhong
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supporting information; experimental part
p. 8891 - 8895
(2012/09/25)
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- Synthesis of carbamates from amines and dialkyl carbonates: Influence of leaving and entering groups
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A number of carbamates were synthesised through a halogen-free process by reacting amines with symmetrical and unsymmetrical carbonates. The results obtained showed a specific trend of preferred leaving groups (in the dialkyl carbonates) depending on whether a catalyst or a base was used. On the other hand, investigations conducted on the preferred entering groups (amines) for the synthesis of carbamates showed the same trend regardless of whether a catalyst or a base was used. Finally, in accordance with the results obtained, it was possible to synthesise sterically hindered carbamates in high yield by transesterification of methyl carbamate with a sterically hindered alcohol. Georg Thieme Verlag Stuttgart New York.
- Tundo, Pietro,McElroy, C. Robert,Aricò, Fabio
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experimental part
p. 1567 - 1571
(2010/09/05)
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- Direct fixation of [11C]-CO2 by amines: Formation of [11C-carbonyl]-methylcarbamates
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[11C-Carbonyl]-methylcarbamates can be synthesised directly from [11C]-CO2 and primary or secondary amines in a one-pot, two-step reaction. The use of either diazabicyclo[5.4.0]undec-7-ene (DBU) or 2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine (BEMP) enables efficient trapping of [11C]-CO2 in small volumes of DMF as [11C]-carbamate salts. Subsequent reaction with a variety of methylating agents rapidly generates the desired [ 11C-carbonyl]-methylcarbamates in high radiochemical yields. The usefulness of the method is illustrated by the efficient radiosynthesis of a kappa opioid receptor imaging radiotracer, useful in positron emission tomography (PET).
- Wilson, Alan A.,Garcia, Armando,Houle, Sylvain,Vasdev, Neil
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experimental part
p. 428 - 432
(2010/02/16)
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- Trapping of carbamic acid species with (trimethylsilyl)diazomethane
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Methoxycarbonylation of a variety of amines into the corresponding methyl carbamates was accomplished by allowing them to react with (trimethylsilyl) diazomethane TMSCHN2 under bubbling of CO2. The reaction was performed at room temperature for a period of ca. 2 h in benzene-MeOH (4/1 v/v), which was the solvent of choice. In this mixed solvent, undesirable bicarbonate is formed in equilibrium along with carbamate anion. Owing to the irreversibility in the esterification step by TMSCHN2, however, the yield of methyl carbamate can reach very high.
- Ito, Yoshikatsu,Ushitora, Hiromi
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p. 226 - 235
(2007/10/03)
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- Pictet-Spengler reactions in multiphasic supercritical carbon dioxide/CO2-expanded liquid media. In situ generation of carbamates as a strategy for reactions of amines in supercritical carbon dioxide
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Acyl-Pictet-Spengler cyclizations can be achieved in scCO 2/CO2-expanded liquid media via the in situ formation of carbamate derivatives of β-arylethylamines. The Royal Society of Chemistry 2005.
- Dunetz, Joshua R.,Ciccolini, Rocco P.,Froeling, Morgan,Paap, Scott M.,Allen, Andrew J.,Holmes, Andrew B.,Tester, Jefferson W.,Danheiser, Rick L.
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p. 4465 - 4467
(2007/10/03)
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- Synthesis of methyl carbamates from primary aliphatic amines and dimethyl carbonate in supercritical CO2: Effects of pressure and cosolvents and chemoselectivity
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(Chemical Equation Presented) At 130 °C, in the presence of CO 2 (5-200 bar), primary aliphatic amines react with dimethyl carbonate (MeOCO2Me, DMC) to yield methyl carbamates (RNHCO2Me) and N-methylation side-products (RNHMe and RNMe2). The pressure of CO2 largely influences both the reaction conversion and the selectivity toward urethanes: in general, conversion goes through a maximum (70-80%) in the midrange (40 bar) and drops at lower and higher pressures, whereas selectivity is continuously improved (from 50% up to 90%) by an increase of the pressure. This is explained by the multiple role of CO2 in (i) the acid/base equilibrium with aliphatic amines, (ii) the reactivity/solubility of RNHCO2- nucleophiles with/in DMC, and (iii) the inhibition of competitive N-methylation reaction of the substrates. Cosolvents also affect the reaction: in particular, a drop in selectivity is observed with polar protic media (i.e., MeOH), plausibly because of solvation effects (through H-bonds) of RNHCO2- moieties. The reaction shows also a good chemoselectivity: bifunctional aliphatic amines bearing either aromatic NH2 or OH substituents [XC6H4(CH2)nNH2, X = NH2, OH; n = 1 2], undergo methoxycarbonylation reactions exclusively at aliphatic amino groups and give the corresponding methyl carbamates [XC 6H4(CH2)nNHCO2Me] in 39-65% isolated yields.
- Selva, Maurizio,Tundo, Pietro,Perosa, Alvise,Dall'Acqua, Federico
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p. 2771 - 2777
(2007/10/03)
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- Copper-Mediated N-Alkynylation of Carbamates, Ureas, and Sulfonamides. A General Method for the Synthesis of Ynamides
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(Matrix Presented) A general amination strategy for the N-alkynylation of carbamates, sulfonamides, and chiral oxazolidinones and imidazolidinones is described. A variety of substituted ynamides are available by deprotonation of amides with KHMDS followed by reaction with CuI and an alkynyl bromide.
- Dunetz, Joshua R.,Danheiser, Rick L.
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p. 4011 - 4014
(2007/10/03)
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- Efficient Cs2CO3-promoted solution and solid phase synthesis of carbonates and carbamates in the presence of TBAI
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Novel solution and solid-phase methods for the synthesis of carbonates and carbamates were developed using cesium bases and TBAI via a three-component coupling. Cesium carbonate not only promoted successful carbonylations of alcohols and carbamations of amines, but also suppressed common side reactions traditionally seen using existing protocols. Various alcohols and amines were examined, using a wide array of alkyl halides, and the results demonstrated this methodology was highly chemoselective. In particular, use of either sterically demanding substrates or amino acid derivatives afforded the corresponding products exclusively, offering a wide variety of applications such as novel protecting groups and peptidomimetic syntheses.
- Salvatore, Ralph N,Chu, Feixia,Nagle, Advait S,Kapxhiu, Elona A,Cross, Richard M,Jung, Kyung Woon
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p. 3329 - 3347
(2007/10/03)
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- A new route to 7-substituted derivatives of N-{4-[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl) -ethyl]benzoyl}-L-glutamic acid [ALIMTA (LY231514, MTA)]
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Alkylation of various primary amines with crotyl bromide, followed by DMAP-promoted acylation with methyl malonyl chloride to 4 and then manganic triacetate dihydrate/cupric acetate induced radical cyclization, gave 1-substituted-4-vinyl-3-carbomethoxy-2-pyrrolidinones (5). Thiation to the thiolactams 6 and guanidine cyclization then gave a series of 2-amino-3,4-dihydro-4-oxo-5-vinyl-7-substituted pyrrolo[2,3-d]pyrimidines (7). Palladium-catalyzed C-C coupling with diethyl 4-iodobenzoylglutamate led in one step via an unexpected redox reaction to the diethyl esters 9 of a series of 7-substituted derivatives of ALIMTA (LY231514, MTA), from which the target analogues 10 were readily prepared by saponification. Attempted deprotection at position 7 was successful in only one case (9d, R = CH2C6H3(OMe)2 (-3′,4′), which resulted in a known pentultimate precursor (9, R = H) of ALIMTA. The 7-substituted derivatives 10 proved to be inactive in vitro as inhibitors of cell division.
- Taylor,Liu
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p. 3726 - 3738
(2007/10/03)
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- ANTITHROMBOTIC AGENTS
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This invention relates to thrombin inhibiting compounds having the Formula IX--Y--NH--(CH 2) r--G I where X, Y, r and G have the values defined in the description, as well as pharmaceutical formulations containing those compounds and methods of their use as thrombin inhibitors, coagulation inhibitors, and thromboembolic disorder agents.
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- Multilevel selectivity in the mild and high-yielding chlorosilane- induced cleavage of carbamates to isocyanates
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The silane-induced cleavage of a series of N-p-tolylcarbamates and N- phenethylcarbamates to isocyanates has been investigated as a function of chlorosilane, carbamate substituent, and reaction conditions. Reaction yields were determined from the isolated ureas, which were formed by trapping the corresponding isocyanates with isobutylamine. Under room-temperature conditions, multilevel selectivity in carbamate activation has been demonstrated. This selectivity together with the generality of the methodology enhances the utility of carbamates as synthetic intermediates and protecting groups. To demonstrate the effectiveness of this selectivity, a series of biscarbamates were selectively monoactivated to isocyanates in excellent yields.
- Chong, Pek Y.,Janicki, Slawomir Z.,Petillo, Peter A.
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p. 8515 - 8521
(2007/10/03)
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- ANTITHROMBOTIC AGENTS
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This invention relates to thrombin inhibiting compounds having the FormulaIX--Y--NH--(CH 2) r--G I where X, Y, r and G have the values defined in the description, as well as pharmaceutical formulations containing those compounds and methods of their use as thrombin inhibitors, coagulation inhibitors, and thromboembolic disorder agents.
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- ANTITHROMBOTIC AGENTS
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This invention relates to thrombin inhibiting compounds having the FormulaIX--Y--NH--(CH 2) r--G I where X, Y, r and G have the values defined in the description, as well as pharmaceutical formulations containing those compounds and methods of their use as thrombin inhibitors, coagulation inhibitors, and thromboembolic disorder agents.
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- ANTITHROMBOTIC AGENTS
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This invention relates to thrombin inhibiting compounds having the FormulaIX--Y--NH--(CH 2) r--G I where X, Y, r and G have the values defined in the description, as well as pharmaceutical formulations containing those compounds and methods of their use as thrombin inhibitors, coagulation inhibitors, and thromboembolic disorder agents.
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- ANTITHROMBOTIC AGENTS
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This invention relates to thrombin inhibiting compounds having the FormulaIX--Y--NH--(CH 2) r--G I where X, Y, r and G have the values defined in the description, as well as pharmaceutical formulations containing those compounds and methods of their use as thrombin inhibitors, coagulation inhibitors, and thromboembolic disorder agents.
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- Bicyclic fibrinogen antagonists
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This invention relates to compounds of the formula: STR1 which are effective for inhibiting platelet aggregation, pharmaceutical compositions for effecting such activity, and a method for inhibiting platelet aggregation.
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- ELECTROCHEMICAL AND PHOTOCHEMICAL PREPARATION OF N-ACYLATED α-METHOXY-PHENETHYLAMINE. FAILURE TO CONVERSION INTO PHENYLALANINE.
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Anodic oxidation of N-methoxycarbonyl phenethylamine in MeOH at pH 9 proceeds quantitatively although only 45percent conversion can be reached in a simple undivided electrocell as the result of the formation of an obstructing precipitate.Treatment of several N-acyl-α-methoxy derivatives with cyanide results in elimination instead of substitution.The preparation of Phe from the above-mentioned synthons therefore was unsuccessfull.
- Callens, R.,Anteunis, M. J. O.,Witte, M. De
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p. 619 - 622
(2007/10/02)
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