- Cell Permeable Imidazole-Desferrioxamine Conjugates: Synthesis and in Vitro Evaluation
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Desferrioxamine (DFO), a clinically approved iron chelator used for iron overload, is unable to chelate labile plasma iron (LPI) because of its limited cell permeability. Herein, alkyl chain modified imidazolium cations with varied hydrophobicities have been conjugated with DFO. The iron binding abilities and the antioxidant properties of the conjugates were found to be similar to DFO. The degree of cellular internalization was much higher in the octyl-imidazolium-DFO conjugate (IV) compared with DFO, and IV was able to chelate LPI in vitro. This opens up a new avenue in using N-alkyl imidazolium salts as a delivery vector for hydrophilic cell-impermeable drugs.
- Pramanik, Shreya,Chakraborty, Saikat,Sivan, Malavika,Patro, Birija S.,Chatterjee, Sucheta,Goswami, Dibakar
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Read Online
- Synergistic cooperation of bi-active hydrogen atoms in protic carboxyl imidazolium ionic liquids to push cycloaddition of CO2 under benign conditions
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Nine protic carboxyl imidazolium ionic liquids are synthesized. Then, they are employed to catalyze the chemical fixation of carbon dioxide (CO2) and propylene oxide leading to propylene carbonate in the absence of co-catalyst and organic solvent. HCPImBr presents the best catalytic activity with the product yield of 92% under reaction temperature 120 °C, CO2 initial pressure 1.5 MPa, catalyst amount 0.5 mol%, and reaction time 2.0 h. Even if the reaction temperature and CO2 initial pressure are decreased to 80 °C and 1.0 MPa, respectively, the 85% of product yield would be kept with the 1.0% catalyst dosage along with 12.0 h. With the exception of the most optimal reaction conditions, generality, and recyclability of HCPImBr are also investigated. More importantly, the reaction mechanism is investigated by the density functional theory, which is the first time to report the mechanism for protic carboxyl imidazolium ionic liquids. The catalytic activity of ionic liquids would be further improved with the reasonable combination of cation and anion.
- Wang, Tengfei,Zhu, Xinrui,Mao, Lemin,Liu, Yi,Ren, Tiegang,Wang, Li,Zhang, Jinglai
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- 1,3-Bis(2′-hydroxyethyl)imidazolium ionic liquids: Correlating structure and properties with anion hydrogen bonding ability
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A series of 1,3-bis(2′-hydroxyethyl)imidazolium ionic liquids is reported where 1H NMR chemical shift values and thermal stabilities (Td), as determined by thermogravimetric analysis, are correlated with the hydrogen bonding capability of various anions ([Cl-], [Br-], [CF3CO2-], [NO 2-], [MsO-], [NO3-], [TfO-], [BF4-], [NTf2-], and [PF6-]). Use of anions with the strongest hydrogen bonding capability, such as chloride [Cl-], bromide [Br-], and trifluoroacetate [CF3CO2-], led to the furthest observed downfield chemical shift values in DMSO-d6 and the poorest thermal stabilities ([CF3CO2-] -], tetrafluoroborate [BF4-], or bis(trifluoromethylsulfonyl)imide [NTf2-] anion. Optimized structures of selected ionic liquids, as determined by density functional theory calculations at the B3LYP/6-31G + (d,p) level, indicated that the anion preferred to be located above the imidazolium ring and in close proximity to the hydroxyl groups. Calculated dissociation energies (ΔE) and a comparison of key bonding distances (C2 - H, (C2)H···X, O - H, and (O)H···X) also confirmed this structural preference. Copyright
- Deng, Feng,Reeder, Zachary K.,Miller, Kevin M.
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Read Online
- Copper carbenoid mediated N-alkylation of imidazoles and its use in a novel synthesis of bifonazole
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1H-Imidazoles are readily N-alkylated by a Cu(acac)2 mediated reaction with α-diazocarbonyl compounds or with diazoalkanes generated in situ from the corresponding p-toluensulfonyl hydrazones. The antifungal agent bifonazole was prepared by the latter method. Graphical Abstract.
- Cuevas-Ya?ez, Erick,Serrano, Juan Manuel,Huerta, Gloria,Muchowski, Joseph M.,Cruz-Almanza, Raymundo
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Read Online
- One-pot preparation method for imidazol-1-yl-acetic acid
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The invention discloses a one-pot preparation method for imidazol-1-yl-acetic acid. The preparation method comprises the following specific steps: 1) dissolving imidazole in a solvent, and then carrying out an N-alkylation reaction on the formed solution and an N-alkylation reagent to obtain methyl imidazol-1-yl-acetate or ethyl imidazol-1-yl-acetate in a reaction intermediate state; and 2) addinghydrous ethanol into a reaction solution obtained in the step 1), continuing heating for a hydrolysis reaction, carrying out cooling for crystallization after the reaction is finished, and carrying out filtering and drying to obtain imidazol-1-yl-acetic acid. According to the method, the starting raw material imidazole is used as an alkali, so the use of a phase transfer catalyst is avoided; theimidazol-1-yl-acetic acid is prepared by the one-pot method, so steps are few, operation is simple, raw material variety is few, post-treatment is simple, reaction yield is high, product purity is high, reaction conditions are mild, cost is low, and safety is good; and the method accords with the trend of green chemical industry and is suitable for industrial production.
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Paragraph 0030-0038
(2020/07/15)
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- Multi-active-center ionic liquid, preparation method and method for catalytically synthesizing cyclic carbonate by using multi-active-center ionic liquid
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The invention relates to a novel multi-active-center ionic liquid, the structural formula of which is shown in the specification, in the formula, n is equal to 1, 2 or 3. The invention also provides amethod for catalytically synthesizing cyclic carbonate by using the ionic liquid. The invention solves the problems of low catalyst performance, harsh reaction conditions and use of an organic solvent or a cocatalyst in the existing method for synthesizing cyclic carbonate by using CO2 and an epoxy compound, and uses a novel multi-active center ionic liquid as a catalyst to catalyze the epoxy compound and CO2 to carry out cycloaddition reaction at the pressure of 0.1-0.5 MPa and the temperature of 30-80 DEG C so as to generate cyclic carbonate. The highest yield can reach 98.5%.
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Paragraph 0030-0033
(2020/11/23)
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- Dihydro quinazolinone derivative, as well as preparation method and application thereof
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The invention relates to the technical field of medicines, in particular to a new dihydro quinazolinone derivative with the following chemical structure general formula and pharmaceutically acceptablesalts thereof, (the formula is shown in the description.), A pharmacological experiment shows that the derivative or the salt provided by the invention has higher inhibitory activity on KRAS-PDE delta protein interaction, and has higher anti-tumor activity in vitro. The invention also provides a preparation method of the derivative and the pharmaceutically acceptable salts thereof, and application to preparatioin of a KRAS-PDE delta inhibitor and an anti-tumor drug.
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Paragraph 0117; 0124; 0125
(2018/07/30)
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- Discovery of Molidustat (BAY 85-3934): A Small-Molecule Oral HIF-Prolyl Hydroxylase (HIF-PH) Inhibitor for the Treatment of Renal Anemia
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Small-molecule inhibitors of hypoxia-inducible factor prolyl hydroxylases (HIF-PHs) are currently under clinical development as novel treatment options for chronic kidney disease (CKD) associated anemia. Inhibition of HIF-PH mimics hypoxia and leads to increased erythropoietin (EPO) expression and subsequently increased erythropoiesis. Herein we describe the discovery, synthesis, structure–activity relationship (SAR), and proposed binding mode of novel 2,4-diheteroaryl-1,2-dihydro-3H-pyrazol-3-ones as orally bioavailable HIF-PH inhibitors for the treatment of anemia. High-throughput screening of our corporate compound library identified BAY-908 as a promising hit. The lead optimization program then resulted in the identification of molidustat (BAY 85-3934), a novel small-molecule oral HIF-PH inhibitor. Molidustat is currently being investigated in clinical phase III trials as molidustat sodium for the treatment of anemia in patients with CKD.
- Beck, Hartmut,Jeske, Mario,Thede, Kai,Stoll, Friederike,Flamme, Ingo,Akbaba, Metin,Ergüden, Jens-Kerim,Karig, Gunter,Keldenich, J?rg,Oehme, Felix,Militzer, Hans-Christian,Hartung, Ingo V.,Thuss, Uwe
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p. 988 - 1003
(2018/04/19)
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- Discovery of Novel KRAS-PDEδ Inhibitors by Fragment-Based Drug Design
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Targeting KRAS-PDEδ protein-protein interactions with small molecules represents a promising opportunity for developing novel antitumor agents. However, current KRAS-PDEδ inhibitors are limited by poor cellular antitumor potency and the druggability of the target remains to be validated by new inhibitors. To tackle these challenges, herein, novel, highly potent KRAS-PDEδ inhibitors were identified by fragment-based drug design, providing promising lead compounds or chemical probes for investigating the biological functions and druggability of KRAS-PDEδ interaction.
- Chen, Long,Zhuang, Chunlin,Lu, Junjie,Jiang, Yan,Sheng, Chunquan
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supporting information
p. 2604 - 2610
(2018/03/26)
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- 7-OXO -6-(SULFOOXY)- 1,6-DIAZABICYCLO [3.2.1] OCTANE CONTAINING COMPOUNDS AND THEIR USE IN TREATMENT OF BACTERIAL INFECTIONS
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Compounds of Formula (I) or a stereoisomer or a pharmaceutically acceptable salt thereof, their preparation, and use in treating a bacterial infection are disclosed.
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Page/Page column 51
(2017/06/19)
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- Imidazole heterocyclic diphosphonic acid compound as well as preparation method and application thereof
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The invention belongs to the field of pharmaceutical chemistry, and in particular relates to an imidazole heterocyclic diphosphonic acid compound as well as a preparation method and application thereof. The imidazole heterocyclic diphosphonic acid compound has a larger non-toxic concentration range for an osteoclast precursor, and can significantly inhibit the formation of osteoclasts at the same time; the imidazole heterocyclic diphosphonic acid compound can damage actin ring to the utmost extent, thus having an obvious inhibiting effect on the osteoclasts and further being used as an osteoclast inhibitor; the imidazole heterocyclic diphosphonic acid compound solves the problems that diphosphonate in the prior art is low in inhibiting effect on the osteoclasts, high in toxicity and large in side effects.
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Paragraph 0072; 0073
(2017/07/20)
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- Synthesis of polysiloxane-based quaternized imidazolium salts with a hydroxy group at the end of alkyl groups
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A series of polysiloxane derivatives having quaternized imidazolium moieties with hydroxyalkyl groups ([HPImnOH]Xs) (where n is the number of methylene group and X is counter anion) were prepared by quaternization of poly(3-chloropropylmethylsiloxane) (P1) using 1-(ω-hydroxyalkyl)imidazole derivatives (ImnOHs) and anion-exchange reaction using lithium bis(trifluoromethanesulfonyl)imide. Polysiloxane-based quaternized imidazolium salts having hydroxyalkyl groups with chloride anion ([HPImnOH]Cls) were obtained with high quaternization ratio of approximately 100 mol%. The glass transition temperatures (Tgs) of [HPImnOH]Xs were reduced by introducing a hydroxy group at the end of alkyl groups; however, no significant reduction in Tgs was observed by anion exchange from chloride anion to bis(trifluoromethanesulfonyl)imide one (Tf2N-).
- Ichikawa, Tsukasa,Wako, Tsuyoshi,Nemoto, Nobukatsu
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- Potentiating the Anticancer Properties of Bisphosphonates by Nanocomplexation with the Cationic Amphipathic Peptide, RALA
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Bisphosphonates (BPs) are a class of bone resorptive drug with a high affinity for the hydroxyapatite structure of bone matrices that are used for the treatment of osteoporosis. However, clinical application is limited by a common toxicity, BP-related osteonecrosis of the jaw. There is emerging evidence that BPs possess anticancer potential, but exploitation of these antiproliferative properties is limited by their toxicities. We previously reported the utility of a cationic amphipathic fusogenic peptide, RALA, to traffic anionic nucleic acids into various cell types in the form of cationic nanoparticles. We hypothesized that complexation with RALA could similarly be used to conceal a BP's hydroxyapatite affinity, and to enhance bioavailability, thereby improving anticancer efficacy. Incubation of RALA with alendronate, etidronate, risedronate, or zoledronate provoked spontaneous electrostatic formation of cationic nanoparticles that did not exceed 100 nm in diameter and that were stable over a range of temperatures and for up to 6 h. The nanoparticles demonstrated a pH responsiveness, possibly indicative of a conformational change, that could facilitate release of the BP cargo in the endosomal environment. RALA/BP nanoparticles were more potent anticancer agents than their free BP counterparts in assays investigating the viability of PC3 prostate cancer and MDA-MB-231 breast cancer cells. Moreover, RALA complexation potentiated the tumor growth delay activity of alendronate in a PC3 xenograft model of prostate cancer. Taken together, these findings further validate the use of BPs as repurposed anticancer agents.
- Massey, Ashley S.,Pentlavalli, Sreekanth,Cunningham, Richard,McCrudden, Cian M.,McErlean, Emma M.,Redpath, Philip,Ali, Ahlam A.,Annett, Stephanie,McBride, John W.,McCaffrey, Joanne,Robson, Tracy,Migaud, Marie E.,McCarthy, Helen O.
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p. 1217 - 1228
(2016/04/26)
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- Synthesis of β-hydroxyacetamides from unactivated ethyl acetates under base-free conditions and microwave irradiation
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The amidation of unactivated ethyl esters with achiral and chiral 1,2-amino alcohols under microwave irradiation and base-free conditions is described. This procedure provides a convenient method for the synthesis of β-hydroxyacetamides bearing pyrazole, imidazole, and benzimidazole groups in high yields and without racemization. The protocol described herein is environmentally friendly and allows for the preparation of a wide variety of β-hydroxyacetamides, which are key intermediates in the synthesis of oxazolines and other derivatives of biological interest.
- Hernández-Fernández, Eugenio,Sánchez-Lara, Pedro Pablo,Ordó?ez, Mario,Ramírez-Marroquín, Oscar Abelardo,Avalos-Alanís, Francisco G.,López-Cortina, Susana,Jiménez-Pérez, Víctor M.,Ibarra-Rivera, Tannya Rocio
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- Tetrazolylhydrazides as selective fragment-like inhibitors of the JumonjiC-domain-containing histone demethylase KDM4A
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The JumonjiC-domain-containing histone demethylase 2A (JMJD2A, KDM4A) is a key player in the epigenetic regulation of gene expression. Previous publications have shown that both elevated and lowered enzyme levels are associated with certain types of cancer, and therefore the definite role of KDM4A in oncogenesis remains elusive. To identify a novel molecular starting point with favorable physicochemical properties for the investigation of the physiological role of KDM4A, we screened a number of molecules bearing an iron-chelating moiety by using two independent assays. In this way, we were able to identify 2-(1H-tetrazol-5-yl)acetohydrazide as a novel fragment-like lead structure with low relative molecular mass (Mr=142 Da), low complexity, and an IC50 value of 46.6 μm in a formaldehyde dehydrogenase (FDH)-coupled assay and 2.4 μm in an antibody-based assay. Despite its small size, relative selectivity against two other demethylases could be demonstrated for this compound. This is the first example of a tetrazole group as a warhead in JMJD demethylases. Anchor fragment: To develop non-promiscuous metalloenzyme inhibitors, a metal-complexing acetohydrazide group was integrated in a tetrazolyl fragment, which can be matured into a scaffold to promote further selectivity at the ligand backbone binding site of these emerging drug targets.
- Rüger, Nicole,Roatsch, Martin,Emmrich, Thomas,Franz, Henriette,Schüle, Roland,Jung, Manfred,Link, Andreas
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supporting information
p. 1875 - 1883
(2015/11/10)
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- Design, synthesis and anti-itch activity evaluation of aromatic amino acid derivatives as gastrin-releasing peptide receptor antagonists
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Eight aromatic amino acid derivatives (9a-9h) as gastrin-releasing peptide receptor (GRPR) antagonists were designed and synthesized. For the design, the tertiary structure of GRPR was predicted by blast searching in the premise of 1u19 protein as the template. Eight target compounds were docked into the binding pocket to investigate their possible binding interactions. Their anti-itch activities were tested by intrathecal injection using Kunming mice as experimental animals and chloroquine phosphate as a modeling medium. Compounds 9e and 9f significantly inhibited scratching behaviors. The anti-itch activities of these compounds decreased with the following sequence: 9e > 9f = 9d > 9b > 9g > 9a > 9h > 9c predicted by computer-aided drug design (CADD) and 9e > 9f > 9b > 9h > 9g > 9d > 9a > 9c evaluated by preliminary test. They were broadly in line with activity order pretested by CADD. It showed that the predicted tertiary structure of GRPR could be used for antipruritic drug design.
- Yao, Ri-Sheng,Li, Ting-Ting,Xu, Jun,Jiang, Lai-En,Ruan, Ban-Feng
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p. 865 - 873
(2012/10/29)
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- Synthesis and thermal analysis of crosslinked imidazolium-containing polyester networks prepared by Michael addition polymerization
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Several new covalently crosslinked imidazolium-containing polyester networks were prepared by Michael addition polymerization to probe how ionic functionality might affect thermal properties such as glass transition temperature (Tg) and thermal decomposition (Td5%). A structure-activity relationship was investigated involving a variation of the methylene spacer and the counteranion of the acetoacetate precursors. Analysis of Tg by differential scanning calorimetry (DSC) indicated that a longer methylene spacer (n = 6 versus 2) resulted in lower Tg values due to increased chain mobility. It was also discovered that the larger the counteranion, the lower the Tg(Br->NO3 -≈BF4->CF3CO2 ->NTf2-). Thermogravimetric analysis (TGA) indicated that the thermal stability of the polyesters was inversely related to the basicity of the counteranion used, following the trend: (NTf 2->BF4->N3 ->Br-). The exception was the trifluoroacetate- containing polyester, which exhibited the lowest thermal stability.
- Kim, Sooyeon,Miller, Kevin M.
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p. 5666 - 5674
(2013/01/15)
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- Solid-liquid phase alkylation of n-heterocycles: Microwave-assisted synthesis as an environmentally friendly alternative
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The solid-liquid phase alkylation of a variety of five-membered N-heterocycles (carbazole, imidazole, benzimidazole, and indole-3-carbaldehyde) was carried out under different conditions. The use of alkali carbonate in dimethylformamide or in MeCN (in the latter case, in the presence of a phase-transfer catalyst) is a suitable method to prepare the corresponding N-alkylated products in an efficient way. In most cases, the solventless, microwave-assisted reaction is an environmentally friendly alternative to traditional methods. Copyrigh
- Milen, Matyas,Gruen, Alajos,Balint, Erika,Dancso, Andras,Keglevich, Gyoergy
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experimental part
p. 2291 - 2301
(2010/09/17)
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- SUBSTITUTED DIHYDROPYRAZOLONES FOR TREATING CARDIOVASCULAR AND HEMATOLOGICAL DISEASES
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The invention relates to dihydropyrazolon-derivatives of formula (I), to methods for their production, to their use for treating and/or for preventing diseases and their use for producing medicaments for treating and/or for preventing diseases, in particular cardiovascular and haematological diseases, kidney diseases and for promoting the healing of wounds.
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Page/Page column 25
(2010/12/29)
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- Synthesis and antitubercular screening of imidazole derivatives
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A series of imidazole based compounds were synthesized by reacting simple imidazoles with alkyl halides or alkyl halocarboxylate in presence of tetrabutylammonium bromide (TBAB). The compounds bearing carbethoxy group undergo amidation with different amines in the presence of DBU to give respective carboxamides. The synthesized compounds were screened against Mycobacterium tuberculosis where compound 17 exhibited very good in vitro antitubercular activity and may serve as a lead for further optimization.
- Pandey, Jyoti,Tiwari, Vinod K.,Verma, Shyam S.,Chaturvedi, Vinita,Bhatnagar,Sinha,Gaikwad,Tripathi, Rama P.
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experimental part
p. 3350 - 3355
(2009/12/01)
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- SUBSTITUTED DIHYDROPYRAZOLONES AND THEIR USE
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The present application relates to novel substituted dihydropyrazolone derivatives, processes for their preparation, their use for treatment and/or prophylaxis of diseases and their use for the preparation of medicaments for treatment and/or prophylaxis of diseases, in particular cardiovascular and haematological diseases and kidney diseases, and for promoting wound healing.
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- N-alkylation of N-trimethylsilylimidazole
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The reaction of N-trimethylsilylimidazole with alkyl chloroacetates is studied. This process yields a mixture of N-alkylation and quarternization products in the ratio dependent on the reaction conditions. The reaction mechanism is discussed. 1H NMR data show that high melting point and low solubility of 1-imidazolylacetic acid in organic solvents are evidently caused by the formation of strong intermolecular hydrogen bonds, whereas in water zwitterionic structures with the protonation of both nitrogen atoms are formed.
- Lebedev,Sheludyakov,Lebedeva,Frolov,Shatunov,Ustinova,Kovaleva
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p. 1086 - 1088
(2008/03/11)
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- An efficient and convenient method for synthesis of 1-substituted imidazoles
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A convenient method for the synthesis 1-substituted imidazoles was developed by the reaction of α-bromoketone with lithium imidazolide. The reaction gave the desired products in improved yields without the formation of 1,3-disubstituted imidazolium salts. Treatment of bromoacetaldehyde ethylene acetal, 2-(bromomethyl)tetrahydro-2H-pyran, and N-(bromomethyl)phthalimide with lithium imidazolide also gave the corresponding 1-substituted imidazole in good to excellent yields. Direct reaction of α-bromoketone with imidazole as control experiment afforded undesired 1,3-disubstituted imidazolium salts with the desired mono-substituted products.
- Lin, Chun Min,Wong, Fung Fuh,Huang, Jiann-Jyh,Yeh, Mou-Yung
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p. 1359 - 1370
(2007/10/03)
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- Chemokine receptor binding heterocyclic compounds with enhanced efficacy
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The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).
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- Chloropyridylcarbonyl derivatives
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Novel chloropyridylcarbonyl derivatives of the formula STR1 in which Het is STR2 n is 1 or 2, R1 is hydrogen, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C3-6 alkynyl, optionally substituted phenyl or optionally substituted pyrimidinyl, and R2 and R3, independently of each other, are hydrogen or C1-4 alkyl, and acid addition salts and metal salt complexes thereof, are outstandingly active as microbicides.
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- Synthesis and biological activity of 2-(substituted aryl)-3- (N1-imidazolyl-acetamidyl)-4-oxo-thiazolidines and their 5-arylidine derivatives
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Several 2-(substituted aryl)-3-(N 1-imidazolylacetamidyl)-4-oxo-thiazolidines 4 and 2-(substituted aryl, -3-(N 1-imidazolylacetamidyl)-5-arylidine-4-oxothiazolidines 5 have been synthesised and tested for their biological activity. Their structures have been elucidated on the basis of their elemental analysis and spectral data.
- Lodhi,Srivastava,Srivastava
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p. 899 - 903
(2007/10/03)
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- Aminodiol HIV protease inhibitors. Synthesis and structure - Activity relationships of P1/P1′ compounds: Correlation between lipophilicity and cytotoxicity
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A series of novel aminodiol inhibitors of HIV protease based on the lead compound 1 with structural modifications at P1′ were synthesized in order to reduce the cytotoxicity of 1. We have observed a high degree of correlation between the lipophilicity and the cytotoxicity of this series of inhibitors. It was found that appropriate substitution at the para position of the P1′ phenyl group of 1 resulted in the identification of equipotent (both against the enzyme and in cell culture) compounds (101, 10m, 10n, and 15c) which possess significantly decreased cytotoxicity.
- Chen, Ping,Cheng, Peter T. W.,Alam, Masud,Beyer, Barbara D.,Bisacchi, Gregory S.,Dejneka, Tamara,Evans, Adelaide J.,Greytok, Jill A.,Hermsmeier, Mark A.,Humphreys, W. Griffith,Jacobs, Glenn A.,Kocy, Octavian,Lin, Pin-Fang,Lis, Karen A.,Marella, Michael A.,Ryono, Denis E.,Sheaffer, Amy K.,Spergel, Steven H.,Sun, Chong-Qing,Tino, Joseph A.,Vite, Gregory,Colonno, Richard J.,Zahler, Robert,Barrish, Joel C.
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p. 1991 - 2007
(2007/10/03)
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- Synthesis and regioselective hydrolysis of 2-imidazol-1-ylsuccinic esters
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(±)-2-Imidazol-1-ylsuccinic esters were synthesized by thermal addition of imidazole to either fumaric or maleic esters. Acceleration of the reaction was achieved, in some cases, using microwave heating. These esters underwent an easy regioselective hydrolysis, under neutral conditions, to give the corresponding half-esters: (±)-3-(alkoxycarbonyl)-2-imidazol-1-ylpropionic acids, through either BAC3 or BAL1 mechanisms. Kinetic studies in H2O and D2O as well as 18O and 17O labeling experiments supported the proposed mechanism. The results of these hydrolyses, which depended on the nature of the alcohol moiety, were compared with those obtained with some imidazol-1-ylacetate analogues or with (±)-2-pyrazol-1-yl- and benzimidazol-1-ylsuccinic esters. In general, imidazolylsuccinic esters hydrolyzed faster than the homologous derivatives from pyrazole or benzimidazole.
- Zaderenko,Gil,Ballesteros,Cerdan
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p. 6268 - 6273
(2007/10/02)
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- Hofmann-type elimination in the efficient N-alkylation of azoles: Imidazole and benzimidazole
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A simple and efficient preparation of 1-substituted 1H-azoles (imidazole and benzimidazole) has been developed, which involves a selective Hofmann-type elimination of the 2-cyanoethyl group from the azolium salts obtained by the reaction of halides with 1H-imidazole-1-propanenitrile and 1H-benzimidazole-1-propanenitrile. Overall yields of 1-substituted 1H-azoles decreased in the order: primary alkyl halides ≥ allylhalides ≥ secondary alkyl halides ≥ benzyl halides > α-keto halides, in relation to the alkylating agent, and imidazole ≥ benzimidazole, in relation to the azole, respectively.
- Horvath
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p. 102 - 106
(2007/10/02)
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- An improved and convenient procedure for the synthesis of 1-substituted imidazoles
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1-Protected imidazoles, such as 1-acetyl- and 1-benzoylimidazoles, react with various halides, such as benzyl, allyl, α-keto, and alkyl halides, to give 1-protected-3-substituted imidazolium salts in high yields. The resultant imidazolium salts are easily deprotected by treatment with water or alcohols to give the corresponding 1-substituted imidazoles in excellent yields. In this reaction the yields of 1-substituted imidazoles vary with the kinds of halides used and/or with the protecting groups, and the yields increase in the following order: benzyl halides≥allyl halides~α-keto halides>alkyl halides, and acetyl≥benzoyl>ethoxycarbonyl>diethoxymethyl>trimethylsilyl>tosyl.
- Kamijo,Yamamoto,Harada,Iizuka
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p. 1213 - 1221
(2007/10/02)
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