- Microgels as Matrices for Molecular Receptor and Reactive Sites: Synthesis and Reactivity of Cavities possessing Amino-functions
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Non-fluxional polymeric particles, microgels, have been prepared containing amino-functions situated in cavities in the polymer matrix.The microgels possess binding properties and exhibit greatly enhanced rates of reaction versus isoquinoline-N-sulphonate and 4-nitrophenyl ester substrates compared with simple amines.The polymer reagents possess selectivity against the molecular size of the substrate due to finite cavity size and this selectivity may be modified by variation of pH which causes a change in size of the cavities.
- Hopkins, Andrew,Williams, Andrew
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Read Online
- Activities of 2-phthalimidethanol and 2-phthalimidethyl nitrate, phthalimide analogs devoid of the glutarimide moiety, in experimental models of inflammatory pain and edema
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The reintroduction of thalidomide in the pharmacotherapy greatly stimulated the interest in the synthesis and pharmacological evaluation of phthalimide analogs with new and improved activities and also greater safety. In the present study, we evaluated the activities of two phthalimide analogs devoid of the glutarimide ring, namely 2-phthalimidethanol (PTD-OH) and 2-phthalimidethyl nitrate (PTD-NO), in experimental models of inflammatory pain and edema in male C57BL/6J mice. Intraplantar (i.pl.) injection of carrageenan (300 μg) induced mechanical allodynia and this response was inhibited by previous per os (p.o.) administration of PTD-OH and PTD-NO (750 mg/kg) and also by thalidomide (500 or 750 mg/kg). The edema induced by carrageenan was also inhibited by previous p.o. administration of PTD-OH (500 and 750 mg/kg) and PTD-NO (125, 250, 500 or 750 mg/kg), but not by thalidomide. Carrageenan increased tumor necrosis factor (TNF)-α and CXCL1 concentrations and also the number of neutrophils in the paw tissue. Previous p.o. administration of PTD-NO (500 mg/kg) reduced all the parameters, while PTD-OH (500 mg/kg) reduced only the accumulation of neutrophils. Thalidomide, on the other hand, was devoid of effect on these biochemical parameters. Plasma concentrations of nitrite were increased after p.o. administration of the phthalimide analog coupled to a NO donor, PTD-NO (500 mg/kg), but not after administration of PTD-OH or thalidomide. In conclusion, our results show that small molecules, structurally much simpler than thalidomide or many of its analogs under investigation, exhibit similar activities in experimental models of pain and inflammation. Finally, as there is evidence that the glutarimide moiety contributes to the teratogenic effect of many thalidomide analogs, our results indicate that phthalimide analogs devoid of this functional group could represent a new class of analgesic and anti-inflammatory candidates with potential greater safety.
- Godin, Adriana M.,Araújo, Débora P.,Menezes, Raquel R.,Brito, Ana Mercy S.,Melo, Ivo S.F.,Coura, Giovanna M.E.,Soares, Darly G.,Bastos, Leandro F.S.,Amaral, Flávio A.,Ribeiro, Lucas S.,Boff, Daiane,Santos, Julliana R.A.,Santos, Daniel A.,Teixeira, Mauro M.,De Fátima, ?ngelo,Machado, Renes R.,Coelho, Márcio M.
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Read Online
- Novel synthesis method of N-hydroxyethyl phthalimide
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The invention discloses a novel synthesis method of N-hydroxyethyl phthalimide, which comprises: by taking phthalimide and ethylene oxide as substrates, carrying out nucleophilic substitution reaction to enable the ethylene oxide to be subjected to ring opening, so as to prepare the N-hydroxyethyl phthalimide. According to the method, N,N-dimethylformamide (DMF) or N,N-dimethylacetamide (DMAC) is taken as a solvent, phthalimide and ethylene oxide are directly heated at 100-160 DEG C to react, the temperature is kept to react for a period of time, and then cooling and simple filtering are performed to obtain the N-hydroxyethyl phthalimide with the content of more than 99%. The molar yield can reach 97% or above. No by-product is generated in the whole synthesis production process; after being filtered, the solvent can be applied to the next batch of reaction without treatment, and no process waste is generated in the whole process, so that zero emission of organic synthesis is really realized, and the purpose of clean production is achieved.
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Paragraph 0014-0023
(2021/09/04)
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- Facile synthesis of indolizinoindolone, indolylepoxypyrrolooxazole, indolylpyrrolooxazolone and isoindolopyrazinoindolone heterocycles from indole and imide derivatives
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Chemo-, regio- and diastereoselective coupling reactions of indole with imide derivatives leading to unique heterocyclic systems are demonstrated. Acid-induced 3-position coupling reactions of indole with cyclic imide derived lactamols followed by acid promoted 2-position cyclizations with the corresponding aldehydes are described to obtain the indolizinoindolones and benzoindolizinoindolones. Base induced 2-position coupling reactions ofN-tosylindole withN-(2-iodoethyl)imides and the subsequent cyclizations provide indolylepoxypyrrolooxazole, indolylpyrrolooxazolone and indolyloxazoloisoindolone. Reductive cleavage of indolyloxazoloisoindolone to the corresponding alcohol followed by mesylation and base promotedN-cyclization affords thein situair-oxidized pentacyclic product hydroxyisoindolopyrazinoindolone. A regioisomeric structural revision of the natural product from 1,2,5,6,7,11c-hexahydro-3H-indolizino[7,8-b]indol-3-one to 1,2,5,6,11,11b-hexahydro-3H-indolizino(8,7-b)indol-3-one is also reported in the present studies focussed on the methodologies for heterocyclic synthesis.
- Argade, Narshinha P.,Shelar, Santosh V.
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p. 6160 - 6169
(2021/07/21)
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- FLUORINATED BENZO[F]BENZIMIDAZOL-4-9-DIONE IUM DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS THEREOF AND THEIR USE AS SURVIVIN SUPPRESSANTS
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The present application relates to novel fluorinated derivatives, to processes for their preparation, to compositions comprising them, and to their use in therapy. More specifically, it relates to compounds useful in the treatment of diseases, disorders or conditions mediated by survivin inhibition. In particular, the present application includes compounds of Formula (I) or (II), and compositions and uses thereof: (Formulae (I) (II)).
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Paragraph 00176; 00178
(2020/09/30)
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- Synthesis method of 2-(phthalimido)ethanesulfonyl chloride
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The invention discloses a synthesis method of 2-(phthalimido)ethanesulfonyl chloride. The specific reaction steps are as follows: (1) taking phthalic anhydride and ethanolamine as raw materials, and preparing to obtain N-(2-hydroxyethyl)phthalimide at appropriate temperature and in an appropriate solvent; (2) reacting the N-(2-hydroxyethyl)phthalimide synthesized in the step (1) with thiourea under appropriate temperature and solvent conditions, to obtain an isothiourea compound; (3) reacting the isothiourea compound synthesized in the step (2) under appropriate chlorination reagent, temperature and solvent conditions to obtain 2-(phthalimido)ethanesulfonyl chloride. A novel synthetic route is adopted to prepare 2-(phthalimido)ethanesulfonyl chloride, and the target product obtained by theprocess has high purity, reaction conditions are mild, the yield is high, the operation is simple and convenient, the production cost is low, and the suitability for amplifying production is achieved.
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Paragraph 0033; 0034; 0037; 0038; 0041; 0042; 0045; 0046
(2019/03/28)
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- Synthesis process of amlodipine besylate
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The invention discloses a synthesis process of amlodipine besylate, relates to the technical field of medicine synthesis and solves the problems of low product purity and poor product quality controllability of products prepared by the existing synthesis process. According to the synthesis process, phthalic anhydride is used as raw materials; the parameters of the synthesis process are controlled;the technical flow process is shortened; the synthesis cost is reduced; the product yield is as high as 91 percent; the purity of the prepared amlodipine besylate is as high as 99.5 percent. The self-made amlodipine besylate are used as raw materials for further preparing the amlodipine besylate tablets; the product cost is reduced; the product quality controllability is high.
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Paragraph 0006; 0014; 0015; 0018; 0019
(2018/09/14)
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- Delta-aminoalkylbenzofuranol ethers, and preparation method and application thereof
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The invention relates to delta-aminoalkylbenzofuranol ethers represented by chemical structural formula I shown in the description, and an application thereof in the preparation of herbicides. In thechemical structural formula I, R is selected from C1-C2 alkyl groups, and n is selected from 2, 3 and 4.
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Paragraph 0026-0029
(2018/04/01)
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- Nucleophilic Substitutions of Alcohols in High Levels of Catalytic Efficiency
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A practical method for the nucleophilic substitution (SN) of alcohols furnishing alkyl chlorides, bromides, and iodides under stereochemical inversion in high catalytic efficacy is introduced. The fusion of diethylcyclopropenone as a simple Lewis base organocatalyst and benzoyl chloride as a reagent allows notable turnover numbers up to 100. Moreover, the use of plain acetyl chloride as a stoichiometric promotor in an invertive SN-type transformation is demonstrated for the first time. The operationally straightforward protocol exhibits high levels of stereoselectivity and scalability and tolerates a variety of functional groups.
- Stach, Tanja,Dr?ger, Julia,Huy, Peter H.
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supporting information
p. 2980 - 2983
(2018/05/28)
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- Synthesis technology of amlodipine maleate
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The invention discloses a synthesis technology of amlodipine maleate and relates to the technical field of medicine synthesis, aiming at solving the problem in an existing synthesis technology that more byproducts and impurities exist in industrial production. By controlling parameters of the synthesis technology and reducing the content of the impurities, the purity of the prepared amlodipine maleate reaches 99.5 percent; the self-made amlodipine maleate is used as a raw material for further preparing the amlodipine maleate, so that the cost of a product is reduced and the quality controllability of the product is strong.
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Paragraph 0013; 0014
(2018/09/08)
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- Substituent Effects on the pH Sensitivity of Acetals and Ketals and Their Correlation with Encapsulation Stability in Polymeric Nanogels
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The effect of structural variations in acetal- and ketal-based linkers upon their degradation kinetics is studied through the design, synthesis, and study of six series of molecules, comprising a total of 18 different molecules. Through this systematic study, we show that the structural fine-tuning of the linkers allows access to variations in kinetics of degradation of more than 6 orders of magnitude. Hammett correlations show that the ρ value for the hydrolysis of benzylidene acetals is about ?4.06, which is comparable to an SN1-like process. This shows that there is a strong, developing positive charge at the benzylic position in the transition state during the degradation of acetals. This positively charged transition state is consistent with the relative degradation rates of acetals vs ketals (correlated to stabilities of 1°, 2°, and 3° carboxonium ion type intermediates) and the observed effect of proximal electron-withdrawing groups upon the degradation rates. Following this, we studied whether the degradation kinetics study correlates with pH-sensitive variations in the host-guest characteristics of polymeric nanogels that contains these acetal or ketal moieties as cross-linking functionalities. Indeed, the trends observed in the small molecule degradation have clear correlations with the encapsulation stability of guest molecules within these polymeric nanogels. The implications of this fundamental study extend to a broad range of applications, well beyond the polymeric nanogel examples studied here.
- Liu, Bin,Thayumanavan
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p. 2306 - 2317
(2017/02/23)
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- Nano-Magnetic Sulfonic Acid Catalyzed Facile Synthesis of Diverse Amide Derivatives
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The excellent surface catalytic potential of Fe3O4-OSO3H is utilized in the synthesis of symmetrically and unsymmetrically substituted urea derivatives via transamidation reactions. The scope of the surface catalysis is further extended in transamidation reactions of cyclic and acyclic amide derivatives, and in the amidation of fatty acids. In both transamidation and amidation reactions, the catalyst is reusable up to five times without significant loss in its activity.
- Kothandapani, Jagatheeswaran,Ganesan, Asaithampi,Ganesan, Subramaniapillai Selva
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p. 685 - 692
(2017/01/25)
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- Method for synthesizing phthaloyl amlodipine
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The invention relates to the field of drug synthesis, particularly to a method for synthesizing phthaloyl amlodipine. The method for synthesizing the phthaloyl amlodipine comprises the following steps: (1) synthesis of N-hydroxyethyl phthalimide; (2) synthesis of ethyl-4-(2-phthaloyl ethoxy) ethyl acetoacetate, wherein the ethyl-4-(2-phthaloyl ethoxy) ethyl acetoacetate is prepared by enabling the N-hydroxyethyl phthalimide to react with 4-chloroacetoacetate under a certain condition; (3) synthesis of phthaloyl amlodipine, wherein a target product is obtained by adding 2-chlorobenzaldehyde, acetic acid, piperidine and beta-methyl aminocrotonate to the ethyl-4-(2-phthaloyl ethoxy) ethyl acetoacetate in sequence under a certain condition to react with the ethyl-4-(2-phthaloyl ethoxy) ethyl acetoacetate, adding acetic acid to a reaction product after the reaction, and crystallizing, filtering, washing and drying the reaction product and the acetic acid. The method for synthesizing the phthaloyl amlodipine, provided by the invention, is efficient and easy to operate and can prepare the phthaloyl amlodipine with high yield and excellent quality.
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Paragraph 0028; 0029; 0030
(2017/07/21)
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- Transition State-Based Sialyltransferase Inhibitors: Mimicking Oxocarbenium Ion by Simple Amide
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In the new transition-state based sialyltransferase inhibitors, an amide group was placed at the corresponding C-2 position of CMP-sialic acid to mimic the geometry and charge distribution in the transition state, and simple aromatic or aliphatic rings were used instead of the sialic acid moiety. All synthetic compounds exhibited excellent α(2-6)-sialyltransferase inhibition, resulting in up to a 2600-fold higher affinity for the enzyme than CMP-Neu5Ac, suggesting that amide is a key element for simulating transition-state features.
- Guo, Jian,Li, Wenming,Xue, Weiwei,Ye, Xin-Shan
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supporting information
p. 2135 - 2141
(2017/03/17)
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- Amplification of a FRET Probe by Lipid–Water Partition for the Detection of Acid Sphingomyelinase in Live Cells
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Real-time monitoring of acid sphingomyelinase (ASM) activity is crucial for investigating its role in lipid-mediated signaling processes. In this study, we synthesized fluorescent phosphosphingolipids capable of FRET by phosphorodichloridate chemistry. These sphingomyelin analogues are substrates for recombinant human ASM and can be used to monitor ASM activity by fluorescence spectroscopy. Incubation with cell lysates from wild-type and knock-out mice further confirmed probe cleavage to be exclusive to ASM. We also systematically exploited the environmental sensitivity of the fluorophores to achieve significant increases in responsiveness. This concept may be transferred to other lipid probes in the future. The ASM activity in live cells was imaged by two-photon-excitation microscopy.
- Pinkert, Thomas,Furkert, David,Korte, Thomas,Herrmann, Andreas,Arenz, Christoph
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supporting information
p. 2790 - 2794
(2017/02/26)
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- Synthetic method for furan diamine drug intermediate N-(2-ethoxyl) phthalimide
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The invention relates to a synthetic method for furan diamine drug intermediate N-(2-ethoxyl) phthalimide. The synthetic method includes the following steps that 0.43 mol of phthalic anhydride, 0.05 mol of cuprous chloride, 300 ml of pyridine and 0.44-0.46 mol of ethanol hydroxylamine are added into a reaction vessel provided with a stirrer, a thermometer and a reflux condenser, the solution temperature is slowly raised, a reflux reaction is conducted for 3-4 h at the temperature of 205 DEG C-215 DEG C, the solution temperature is reduced to 10 DEG C-minus 15 DEG C to separate a solid, the solid is added into 500 ml of a xylene solution, the solution temperature is reduced to 3 DEG C-minus 5 DEG C to separate a solid, the solid is sequentially washed with a salt solution, dehydrated with a dehydrating agent and recrystallized in ethyl acetate to obtain a white solid N-(2-ethoxyl) phthalimide. In the steps, the mass fraction of pyridine is 85-90%, and the mass fraction of the xylene solution is 55-60%.
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Paragraph 0014; 0015
(2016/12/01)
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- Insights into the Pummerer synthesis of oxazolines
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A rapid and simple method to access unnatural 2-substituted 5-thio oxazolines has been developed. This methodology is based on a Pummerer reaction followed by an intramolecular nucleophilic substitution, which changes the paradigm for the normal use of a base in Pummerer chemistry. We also provide a useful two-step method for the synthesis of the starting material and a mechanistic proposal based on experimental observations, which contests the previously proposed reaction pathway. The reaction proved to be general, and different substituents, such as alkyl, aryl, alkenyl and functionalized groups, can be used without a significant decrease in efficiency.
- Becerra-Cely, Laura,Rueda-Espinosa, Juan,Ojeda-Porras, Andrea,Gamba-Sánchez, Diego
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p. 8474 - 8485
(2016/09/28)
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- Synergistic Kinetic Resolution and Asymmetric Propargyl Claisen Rearrangement for the Synthesis of Chiral Allenes
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The asymmetric propargyl Claisen rearrangement provides a convenient entry to chiral allene motifs. Herein, we describe the development of a kinetic resolution and asymmetric rearrangement of racemic propargyl vinyl ethers. This transformation afforded chiral allene products along with the enantiomerically enriched substrate in good yields with excellent diastereo- and enantioselectivity. The complete chirality transfer and facially selective rearrangement enabled the simultaneous construction of an axially chiral allenic unit and a quaternary carbon stereocenter.
- Liu, Yangbin,Liu, Xiaohua,Hu, Haipeng,Guo, Jing,Xia, Yong,Lin, Lili,Feng, Xiaoming
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supporting information
p. 4054 - 4058
(2016/03/19)
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- Cuprous Oxide Catalyzed Oxidative C-C Bond Cleavage for C-N Bond Formation: Synthesis of Cyclic Imides from Ketones and Amines
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Selective oxidative cleavage of a C-C bond offers a straightforward method to functionalize organic skeletons. Reported herein is the oxidative C-C bond cleavage of ketone for C-N bond formation over a cuprous oxide catalyst with molecular oxygen as the oxidant. A wide range of ketones and amines are converted into cyclic imides with moderate to excellent yields. In-depth studies show that both α-C-H and β-C-H bonds adjacent to the carbonyl groups are indispensable for the C-C bond cleavage. DFT calculations indicate the reaction is initiated with the oxidation of the α-C-H bond. Amines lower the activation energy of the C-C bond cleavage, and thus promote the reaction. New insight into the C-C bond cleavage mechanism is presented.
- Wang, Min,Lu, Jianmin,Ma, Jiping,Zhang, Zhe,Wang, Feng
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supporting information
p. 14061 - 14065
(2016/01/25)
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- Transamidation of carboxamides catalyzed by Fe(III) and water
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The highly efficient transamidation of several primary, secondary, and tertiary amides with aliphatic and aromatic amines (primary and secondary) is described. The reaction is performed in the presence of a 5 mol % concentration of different hydrated salts of Fe(III), and the results show that the presence of water is crucial. The methodology was also applied to urea and phthalimide to demonstrate its versatility and wide substrate scope. An example of its use is an intramolecular application in the synthesis of 2,3-dihydro-5H-benzo[b]-1,4- thiazepin-4-one, which is the bicyclic core of diltiazem and structurally related drugs (Budriesi, R.; Cosimelli, B.; Ioan, P.; Carosati, E.; Ugenti, M. P.; Spisani, R. Curr. Med. Chem. 2007, 14, 279-287). A plausible mechanism that explains the role of water is proposed on the basis of experimental observations and previous mechanistic suggestions for transamidation reactions catalyzed by transition metals such as copper and aluminum. This methodology represents a significant improvement over other existing methods; it can be performed in air and with wet or technical grade solvents.
- Becerra-Figueroa, Liliana,Ojeda-Porras, Andrea,Gamba-Sánchez, Diego
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p. 4544 - 4552
(2014/06/09)
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- Benzoic acid-catalyzed transamidation reactions of carboxamides, phthalimide, ureas and thioamide with amines
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An efficient and simple method for the transamidation of carboxamides, phthalimide, ureas and thioamide with amines catalyzed by commercially available benzoic acid under metal-free conditions is described. Furthermore, to the best of our knowledge, this is the first report about the transamidation of an aromatic thioamide with amines.
- Wu, Ji-Wei,Wu, Ya-Dong,Dai, Jian-Jun,Xu, Hua-Jian
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supporting information
p. 2429 - 2436
(2014/09/30)
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- Multimetallic iridium-tin (Ir-Sn3) catalyst in N-acyliminium ion chemistry: Synthesis of 3-substituted isoindolinones via intra- and intermolecular amidoalkylation reaction
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The multimetallic iridium-tritin (Ir-Sn3) complex [Cp*Ir(SnCl3)2{SnCl2(H2O) 2}] (1) proved to be a highly effective catalyst towards C-OH bond activation of γ-hydroxylactams, leading to a nucleophilic substitution reaction known as the α-amidoalkylation reaction. Catalyst 1 can be easily synthesized from the reaction of (pentamethylcyclocyclopentadienyl)iridium dichloride dimer {[Cp*IrCl2]2} and tin(II) dichloride (SnCl2). In terms of catalyst loading, reaction conditions and yields of the product formed, 1 is found to be superior compared to classical Lewis acid catalysts. Different carbon (arenes, heteroarenes, allyltrimethylsilane, 1,3-dicarbonyls) and heteroatom (alcohols, thiols, amides and sulfonamides) nucleophiles have been successfully employed in the intramolecular and intermolecular alkylations, as well as in heterocyclization reactions. In the majority of cases good to excellent yields of 3-substituted isoindolinones and 5-substituted pyrrolidin-2-ones have been obtained. Besides, the reactions are also atom economical and salt free. It is proposed that the multimetallic Ir-Sn3 catalyst behaves as a mild and selective Lewis acid to activate the γ-hydroxylactam towards the formation of the N-acyliminium ion; the latter being trapped by potent nucleophiles leading to the desired products.
- Maity, Arnab Kumar,Roy, Sujit
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p. 2627 - 2642
(2014/09/30)
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- Multkilogram scale-up of a reductive alkylation route to a novel PARP inhibitor
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Novel PARP inhibitor 1 is a promising new candidate for treatment of breast and ovarian cancer. A modified synthetic route to 1 has been developed and demonstrated on 7 kg scale. In order to scale up the synthesis to multikilogram scale, several synthetic challenges needed to be overcome. The key issues included significant thermal hazards present in a Leimgruber-Batcho indole synthesis, a low-yielding side-chain installation, a nonrobust Suzuki coupling and hydrogen cyanide generation during a reductive amination. In addition to these issues, changing from intravenous to oral delivery required a new salt form and therefore a new crystallization procedure. This contribution describes development work to solve these issues and scaling up of the new process in the pilot plant.
- Gillmore, Adam T.,Badland, Matthew,Crook, Clare L.,Castro, Nieves M.,Critcher, Douglas J.,Fussell, Steven J.,Jones, Katherine J.,Jones, Matthew C.,Kougoulos, Eleftherios,Mathew, Jinu S.,McMillan, Lynne,Pearce, John E.,Rawlinson, Fiona L.,Sherlock, Alexandra E.,Walton, Robert
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p. 1897 - 1904
(2013/03/13)
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- SELECTIVE GLYCOSIDASE INHIBITORS AND USES THEREOF
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The invention is directed to compounds for selectively inhibiting glycosidases, uses of the compounds and pharmaceutical compositions including the compounds, and methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, and/or accumulation or deficiency of O-GlcNAc.
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Page/Page column 141
(2012/05/31)
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- PYRANO[3,2-D]THIAZOL DERIVATIVES AND USES THEREOF AS SELECTIVE GLYCOSIDASE INHIBITORS
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Pyrano[3,2-d]thiazol derivatives of formula (I) for selectively inhibiting glycosidases, uses of the compounds and pharmaceutical compositions including the compounds are disclosed. Methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc are also provided.
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Page/Page column 142
(2012/05/31)
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- PHENOXYPROPANOL DERIVATIVES AND THEIR USE IN TREATING CARDIAC AND CARDIOVASCULAR DISEASES
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A compound of formula I-0, and its pharmaceutically acceptable salt or salts and physiologically hydrolysable derivatives in free form or salt form: wherein Z1 is C1-C4 linear or branched alkyl or alkenyl; R4 is selected from unsubstituted and substituted C3-C8 cycloalkyl, C1-C8 linear or branched alkyl, C2-5 alkenyl, C6-C10 heteroaryl or aryl, or C3-C8 heterocyclyl which may be part unsaturated, and combinations thereof; is linear C2-3 alkylene,; X1 is selected from NH and O; X2 is selected from unsaturated C and unsaturated S; and X3 is selected from NH and CH2; or one of X1 and X3 is a single bond; or X1 is O and X2 and X3 together are a single bond; and R7 is selected from oxo, F, Cl, Br, CN, NH2, NR92, NO2, CF3, OR9, COR9, OCOR9, COOR9, NR9COR9, CONR92 SO2NR92, NR9SO2R9; and R8 is selected from C1-5 alkyl, C1-5 alkoxyl, C2-5 alkenyl or alkynyl, C6-10) aryl and C3-8 cycloalkyl and combinations thereof, which may be unsubstituted or f urther substituted by one or more F, Cl, Br, CN, NH2, NR32, NO2, CF3; and R9 is selected from H and a group R8 as hereinbefore defined; n7 and n8 and the sum thereof are independently selected from zero and the whole number integer 1 to 4; processes for the preparation thereof, compositions and uses.
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Page/Page column 35
(2012/02/01)
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- An improved procedure for the preparation of aminomethyl polystyrene resin and its use in solid phase (peptide) synthesis
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2-Aminoethanol was used to successively replace hydrazine in the preparation of aminomethyl polystyrene resin thereby facilitating purification and by-product removal. The syntheses of the polypeptides ACP (65-74) and oxytocin demonstrated that the use of aminomethyl polystyrene resin prepared in this manner was equal to or better than that prepared using the hydrazine method.
- Harris, Paul W.R.,Yang, Sung Hyun,Brimble, Margaret A.
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experimental part
p. 6024 - 6026
(2011/11/28)
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- Total synthesis and absolute configuration of malyngamide W
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A concise enantioselective synthesis of malyngamide W (1) and its 2′-epimer was described. The strategy was based on three key steps: (1) ozonolysis of compound 11 which was derived from (R)-(-)-carvone 8, followed by copper-iron-catalyzed rearrangement to give the key cyclohex-2-enone intermediate 5, (2) Nozaki-Hiyama-Kishi coupling reaction between aldehyde 4 and iodide 14 to afford alcohol 3, and (3) asymmetric (R)-CBS reduction of the ketone functionality in compound 21 to establish the C-2′ chiral center in the target compound 1. The absolute configuration of malyngamide W (1) was thus confirmed via the synthesis of 1 and 2′-epi-1.
- Qi, Xian-Liang,Zhang, Jun-Tao,Feng, Jian-Peng,Cao, Xiao-Ping
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supporting information; experimental part
p. 3817 - 3824
(2011/06/21)
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- Synthesis of some novel chalcones of phthalimidoester possessing good antiinflammatory and antimicrobial activity
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A new series of methyl-2-[substituted benzylidine]-4-[2-(phthalimide) ethoxy] acetoacetate, 5a-h have been synthesized from the combination of methyl-4-[2-(phthalimido) ethoxy] acetoacetate, 3 and substituted benzaldehyde 4a-h which results in both anti-inflammatory and antimicrobial active compound. These compounds have been characterized by IR, 1H NMR, mass spectral and elemental analysis. These compounds have been subjected to preliminary anti-inflammatory screening using the carrageenan induced rat pow oedema model. Compounds 5a,b,c show marked activity comparable to indomethacin. Compounds 5a,b,c,g show significant antimicrobial activity.
- Gaikwad, Kishor V.,Gaikwad, Sandip V.,Jadhav, Satish B.,Rathod, Shantilal D.
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experimental part
p. 131 - 136
(2010/05/02)
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- Synthesis and biological evaluation of 3-(phthalimidoethyl)-4-(5- substituted isoxazoline and pyrazoline) substituted benzanilides
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3-Phthalimidoethyl benzoic acids 2a-g were prepared by treating N-hydroxy-ethylphthalimide 1 with substituted benzoic acids. The corresponding acid chlorides 3a-g were condensed with 4-aminoacetophenone in the presence of anhydrous potassium carbonate to give 3-phthalimidoethyl-4-acetyl substituted benzanilides 4a-g. The substituted benzanilide derivatives 4a-g were condensed with diverse aromatic aldehydes to afford compounds 5a1-d 7. Compounds 5a1-7...d1-7 on treatment with hydroxylamine hydrochloride and hydrazine dihydrochloride separately in the presence of sodium acetate afforded titled compounds 6a1-7...d2 and 7a1-9. The structures of the newly synthesized compounds have been established by elemental analysis and spectral data and some of the selected compounds have been screened for their antibacterial, antifungal, anthelmintic and hypoglycemic activities.
- Sahu,Azam, Md. Afzal,Banerjee,Choudhury,Sutradhar,Misro
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scheme or table
p. 498 - 503
(2010/06/16)
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- Synthesis of mandelic acid derived phthalimides as a new class of antiinflammatory and antimicrobial agents
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In the present study, a new series of 2-(1,3-dioxo-2,3-dihydro-1H-2- isoindolyl) ethyl 2-hydroxy-2-(substituted phenyl) acetates 6a-e have been synthesized from the combination of N-(2-hydroxy ethyl) phthalimide 5 and substituted mandelic acids 2a-e which resulted in both anti-inflammatory and antimicrobial activity. These compounds have been characterized by IR, 1H NMR, mass spectral and elemental analysis. Among the compounds tested for anti-inflammatory activity, compound 6b and 6c showed significant activity and compound 6d showed potent antibacterial and antifungal activity. The anti-inflammatory activity has been determined by carrageenan induced acute paw oedema in rats. The results are discussed in the text. The in vitro antibacterial and antifungal activity of the compounds have been evaluated by paper disc diffusion method. The minimum inhibitory concentrations (MIC) of the compounds have also been determined by agar streak dilution method.
- Varala, Ravi,Kotra, Vijay,Alam, M. Mujahid,Kumar, N. Ramesh,Ganapaty,Adapa, Srinivas R.
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p. 1243 - 1248
(2008/12/23)
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- Synthesis and biological evaluation of 3-(phthalimidoethyl)-4-substituted cinnamoyl substituted benzanilides
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3-Phthalimidoethyl substituted benzoic acids (2) were prepared by refluxing N-hydroxyethyl phthalimide (1) with substituted benzoic acids. The corresponding acid chlorides (3) were condensed with 4-aminoacetophenone in anhydrous potassium carbonate to give 3-phthalimidoethyl-4-acetyl substituted benzanilides (4). The substituted benzanilide derivatives (4) were condensed with diverse aryl aldehydes to afford the title compounds (5). Compounds (5) were screened for their possible hypoglycemic and in vitro antibacterial activities.
- Sahu,Mishra,Mandal,Choudhury,Sutradhar,Misro
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p. 832 - 834
(2007/10/03)
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- 2,3,4,5-TETRAHYDRO-1H-1,5-BENZODIAZEPINE DERIVATIVE AND MEDICINAL COMPOSITION
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A 2,3,4,5-tetrahydro-1H-1,5-benzodiazepine derivative represented by the generalformula (1): [Chemical formula 1] (1) or a pharmaceutically acceptable saltthereof. They are useful as a therapeutic/preventive agent for diabetes, diabeticnephropathy, or glomerulosclerosis.
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Page/Page column 76-77
(2010/11/30)
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- Organic reactions in ionic liquids: Ionic liquid-promoted efficient synthesis of N-alkyl and N-arylphthalimides
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Phthalic anhydride reacts rapidly with Aromatic and aliphatic amines in ionic liquid [Bmim][PF6] or [Bmim][BF4] at 130°C to give N-aryl and N-alkylphthalimides in excellent yields.
- Le, Zhang-Gao,Chen, Zhen-Chu,Hu, Yi,Zheng, Qin-Guo
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p. 735 - 737
(2007/10/03)
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- Studies on a novel safety-catch linker cleaved by Pummerer rearrangement
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(Equation Presented) We describe the use of a sulfide linkage as a safety-catch linker. This linker is significantly stable to acidic as well as basic conditions and allows transformations to be carried out on solid supports. Moreover, its cleavage is facile by applying Pummerer rearrangement after transforming it to sulfoxide.
- Tai, Chih-Ho,Wu, Hsiao-Ching,Li, Wen-Ren
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p. 2905 - 2908
(2007/10/03)
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- A procedure for preparing N-hydroxyethyl-substituted succinimide and phthalimide
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Conditions of synthesis of N-hydroxyethyl-substituted succinimide and phthalimide by reactions of dicarboxylic acid imides with aminoethanol were optimized.
- Gasanov,Allakhverdiev
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p. 2034 - 2035
(2007/10/03)
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- Thiadiazolyl quinazolones as potential antiviral and antihypertensive agents
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Phthalic anhydride on treatment with β-ethanol amine gives N-hydroxy ethyl phthalimide I which reacts with anthranilic acid in presence of ethanol containing concentrated hydrochloric acid affording 5-(N-ethylphthalimido)- anthranilic acid 2. This on treatment with benzoyl chloride in pyridine gives 6-(N-ethyl phthalimido)-2-phenyl-4-oxo-3, 4-dihydrobenzoxazine 3 which on reaction with 2-amino-5-aralkyl-1, 3, 4-thiadiazoles 4 in pyridine results in the formation of 6-(N-ethylphthalimido)-3-[2′-(5′-aralkyl-1′, 3′, 4′-thiadiazolyl)]-2-phenyl-4-oxo-(3H)-quinazolines 5. The antiviral and antihypertensive activities of 5 have been reported.
- Pandey,Tusi, Sarah,Tusi, Zehra,Raghubir,Dixit,Joshi,Bajpai
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p. 180 - 183
(2007/10/03)
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- ISOLATION OF DIHYDROPYRIDINE DERIVATIVE AND PREPARATION SALTS THEREOF
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The title compound is isolated in pure form by using a crystallization process and converted to its pharmaceutically acceptable salts. The crystallization process affects stability and purity of the amlodipine salts. All known impurities and one unknown impurity, which forms during the synthesis of the amlodipine salts, were isolated, characterized, and synthesized. A new method allowing the quantitative HPLC analysis of all related impurities of amlodipine salts in a single chromatogram was developed.
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- Process for the preparation of anti-ischemic and anti-hypertensive drug amlodipine besylate
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Process for the preparation of anti-ischemic and anti-hypertensive drug amlodipine besylate [2-{(2-aminoethoxy)-methyl-4-(2-chlorophenyl) 3-ethoxy carbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine} benzene sulphonate]. Phthalic anhydride is condensed with monoethanol amine at 150-190° C. The resulting N-(2-hydroxyethyl) phthalimide is coupled with 4-chloroethyl acetoacetate in the presence of sodium hydride in an organic solvent in an inert atmosphere at ?11 to ?15° C. Ethyl-4-[-2(phthalimido) ethoxy] acetoacetate formed is coupled with orthochloro benzaldehyde in the presence of pyridine salt at 70-90° C. Ethyl-2-(2-chloro benzylidine)4-[-2(phthalimido) ethoxy] acetoacetate fanned is condensed with methyl amino crotonate at 20-40° C. in the presence of acetic acid to form phthaloyl amlodipine [2-(2-Phthalimidoethoxy) methyl-3-carboethoxy 1(chlorophenyl)-S-carbomethoxy-6-methyl-1,4-dihydropyridin] which is purified by dissolving in an organic solvent in the ratio 1:2-1:5 w/v and precipitated by the addition of water at 35-60° C. Purified phthaloyl amlodipine is hydrolysed with methylamine in the presence of a protic solvent at 20-50° C. Amlodipine base [2-(aminoethoxy) methyl-3-carboethoxy-4-(2-chlorophenyl)-5-carbomethoxy-6-methyl-1,4-dihydropyridin] formed is reacted with benzene sulfonic acid. The resulting amlodipine besylate is purified in an organic solvent at 30-70° C. and precipitated by the addition of an insoluble solvent.
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- Process for the oxidation of alcohols to aldehydes and ketones in the presence of nitroxyl compounds as catalysts
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An alcohol is oxidized to an aldehyde or a ketone in the presence of a nitroxyl compound as catalyst, wherein the alcohol to be oxidized is contained in an organic liquid phase, and is reacted in the presence of a nitroxyl compound with an aqueous phase comprising an oxidant. The reaction is carried out continuously at a contact time of the phases of from 0.1 s to a maximum of 15 minutes, with intensive mixing of the phases. The process produces high yields with low quantities of other oxidation byproducts.
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- A fast and practical approach to tetrahydropyranylation and depyranylation of alcohols using indium triflate
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Indium triflate-mediated tetrahydropyranylation of alcohols in dichloromethane and depyranylation of these products in aqueous methanol utilizing the same reagent but different molar ratio is described. In addition, indium triflate-promoted conversion of tetrahydropyran ethers to their corresponding acetates has also been described.
- Mineno, Tomoko
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p. 7975 - 7978
(2007/10/03)
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- Protection of amino group as N-phthalyl derivative using microwave irradiation
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The amino groups for various substrates are protected as N-phthalyl derivatives using solvent free neat condition under microwave exposure.
- Khadilkar, Bhushan M.,Madyar, Virendra R.
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p. 1083 - 1085
(2007/10/03)
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- Exploratory studies probing the intermediacy of azomethine ylides in the photochemistry of N-phthaloyl derivatives of α-amino acids and β-amino alcohols
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Exploratory photochemical studies with N-phthaloyl derivatives of glutamic acid, aspartic acid, serine, threonine and analogous carboxylic acids and alcohols have been conducted to determine the generality of azomethine ylide forming decarboxylation and retro-aldol fragmentation reactions. Preferences in the competition between these excited state reaction pathways have been determined by studies with phthalimides which contain both α-amino acid and β-aminoethanol groups.
- Yoon, Ung Chan,Lee, Chan Woo,Oh, Sun Wha,Mariano, Patrick S.
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p. 11997 - 12008
(2007/10/03)
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- Substituted propargylethoxyamido nucleosides, oligonucleotides and methods for using same
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Substituted propargylethoxyamido nucleosides are disclosed having the structure STR1 wherein X is selected from the group consisting of amino alkanoic acid, alkylamino benzoic acid, α-amino acid, and 4-amino-2-butynoic acid. R1 and R2 taken separately are selected from the group consisting of --H, lower alkyl, protecting group, and label; R3 is selected from the group consisting of --H and lower alkyl. B is a 7-deazapurine, purine, or pyrimidine nucleoside base. When B is purine or 7-deazapurine, the sugar moiety is attached at the N9 -position of the purine or deazapurine, and when B is pyrimidine, the sugar moiety is attached at the N1 -position of the pyrimidine. When B is a purine, the adjacent triple-bonded carbon is attached to the 8-position of the purine, when B is 7-deazapurine, the adjacent triple-bonded carbon is attached to the 7-position of the 7-deazapurine, and when B is pyrimidine, the adjacent triple-bonded carbon is attached to the 5-position of the pyrimidine. W1 is selected from the group consisting of --H and --OH. W2 is --OH or a moiety which renders the nucleoside incapable of forming a phosphodiester bond at the 3'-position. W3 is selected from the group consisting of --PO4, --P2 O7, --P3 O10, phosphate analog, and --OH. Additionaly, a primer extension method is provided employing the above X-substituted propargylethoxyamido nucleosides, and polynucleotides including the above X-substituted propargylethoxyamido nucleosides is provided.
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- Propargylethoxyamino nucleotides
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Propargylethoxyamino nucleosides are disclosed having the structure STR1 wherein R1 and R2 are --H, lower alkyl, or label; B is a 7-deazapurine, purine, or pyrimidine nucleoside base; W1 is --H or --OH; W2 is --OH or a moiety which renders the nucleoside incapable of forming a phosphodiester bond at the 3'-position; and W3 is --PO4, --P2 O7, --P3 O10, phosphate analog, or --OH. Additionaly, a primer extension method is provided employing the above propargylethoxyamino nucleosides.
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- Nitrate esters in the generation of amino acid radicals
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Nitrate esters, prepared by treatment of β-hydroxy-α-amino acid derivatives with nitric acid, react with tributyltin hydride to give the corresponding alkoxyl radicals. These radicals readily undergo β-scission, providing a convenient route for the regiocontrolled production of α-carbon-centred amino acid radicals. By examining the partitioning of the alkoxyl radicals between the β-scission process and the competing hydrogen transfer reaction, it has been possible to evaluate the influence of electronic and steric effects on the β-scission reaction and the formation of the carbon-centred radicals.
- Easton, Christopher J.,Ivory, Andrew J.,Smith, Craig A.
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p. 503 - 507
(2007/10/03)
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- New carbamate supports for the preparation of 3'-amino-modified oligonucleotides
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A novel approach for the preparation of oligonucleotides carrying amino groups at the 3'-end is described. Several CPG supports having aminoalkyl groups and 3'-amino-2',3'-dideoxynucleosides linked through base-labile carbamate linkages such as 2-(2- nitrophenyl)ethoxycarbonyl and fluorenylmethoxycarbonyl were prepared using two different strategies. These supports are compatible to the standard solid phase phosphite-triester methodology and yield oligonucleotides containing amino groups at the 3'-end. Several properties of the 3'-amino oligonucleotides, such as nuclease resistance, hybridization, and preparation of oligonucleotide conjugates are discussed.
- Avino, Anna,Garcia, Ramon Gueimil,Albericio, Fernando,Mann, Matthias,Wilm, Matthias,Neubauer, Gitte,Eritja, Ramon
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p. 1649 - 1658
(2007/10/03)
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- Synthesis of isoindolinones via carbonylative cyclisation of 2-(2-bromophenyl)-2-oxazolines by a bimetallic palladium-nickel catalyst system
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2-(2-Bromophenyl)-2-oxazolines react with carbon monoxide (3 atm) in alcohol in the presence of a catalytic amount of a bimetallic palladium-nickel catalyst to give the corresponding isoindolinones in high yields.
- Cho, Chan Sik,Lee, Jae Wook,Lee, Dong Yub,Shim, Sang Chul,Kim, Tae Jeong
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p. 2115 - 2116
(2007/10/03)
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- CARBEPENEM DERIVATIVES
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Carbapenem derivatives which may be utilized as antibiotics and which show strong antibacterial activity against various bacterial strains including Pseudomonas aeruginosa. The compounds containing the derivatives are quite safe and are also stable against hydrolases such as dehyropeptidase (DHP)
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- Photochemistry of N-phthaloyl derivatives of electron-donor-substituted amino acids
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The hydroxy substituted amino acids threonine and serine have been investigated concerning their photochemical behaviour when activated as N-phthaloyl substrates. The methyl esters 1a and 2a solely underwent cleavage of the central C-C single bond to give the glycine derivative 3 and an aldehyde fragment. C-unprotected threonine derivative 1b is converted into a series of products the composition of which depends on solvent polarity and on the electronic state. Three reaction modes were detected for the N-phthaloyl derivatives of the aryl substituted amino acids phenylalanine, tyrosine, and dihydroxyphenylalanine (DOPA): (A) decarboxylation (only for 12a), (B) β-fragmentation, and (C) ring enlargement reaction. Processes B and C are initiated by photo electron transfer (PET), as the solvent dependence revealed. The DOPA derivatives 14a and 14b are the most prominent examples due to their exclusive PET reactivity leading to type C products (18a,b) with high diastereoselectivity (90:10). PET results from the first excited singlet states of 12 and 13, whereas for compounds 14 the corresponding triplet states are involved. The correlation between photochemical reactivity and the fluorescence decay data for compounds 12a,b and 15 is discussed.
- Griesbeck,Henz,Hirt,Ptatschek,Engel,Loffler,Schneider
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p. 701 - 714
(2007/10/02)
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