- Temperature Coefficients of the Rates of Acid-Catalyzed Enolization of Acetone and Ketonization of Its Enol in Aqueous and Acetonitrile Solutions. Comparison of Thermodynamic Parameters for the Keto-Enol Equilibrium in Solution with Those in the Gas Phase
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Rates of hydrogen ion catalyzed enolization of acetone and ketonization of acetone enol were measured over a range of temperatures in water and in acetonitrile solution.The data give ΔH(excit.) = 20.0 +/- 0.1 kcal mol-1, ΔS(excit.) = -12.1 +/- 0.3 cal K-1 mol-1, and ΔH(excit.) = 20.1 +/- 0.5 kcal mol-1, ΔS(excit.) = -5.8 +/- 1.7 cal K-1 mol-1, for enolization in water and acetonitrile, respectively, and ΔH(excit.) = 9.7 +/- 0.4 kcal mol-1, ΔS(excit.) = -8.6 +/- 1.4 cal K-1 mol-1, and ΔH(excit.) = 11.4 +/- 0.2 kcal mol-1, Σ(excit.) = 1.6 +/-0.8 cal K-1 mol-1, for ketonization in water and acetonitrile, respectively.These values lead to ΔH0 = 10.3 +/- 0.4 kcal mol-1, ΔS0 = -3.5 +/- 1.5 cal K-1 mol-1, for the keto-enol equilibrium in water, and ΔH0 = 8.7 +/- 0.6 kcal mol-1, ΔS0 = -7.4 +/- 1.9 cal K-1 mol-1, for the equilibrium in acetonitrile.This is the first determination of thermodynamic parameters for a simple ketone-enol equilibrium in solution; the results are remarkably similar to the thermodynamic parameters for this reaction in the gas phase.A mechanism involving acid catalysis of the bromination of acetone enol by N-bromosuccinimide, the process used to monitor enolization in acetonitrile solution, is ruled out.
- Chiang, Y.,Kresge, A. J.,Schepp, N. P.
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Read Online
- Effect of initial reagent concentrations on the oscillatory behavior of the BZ reaction in a batch reactor
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A detailed investigation on resorcinol as the Belousov-Zhabotinsky (BZ) oscillator in manganese(II) ion catalyzed reaction system with inorganic bromate (oxidant) and acetone (cosubstrate) was carried out in aqueous sulfuric acid medium (1.3 M). The aforesaid reagents were mixed with various concentrations to evolve the effective concentrations at which the reaction system exhibited better oscillations. The various oscillatory parameters such as time period (t p ), induction period (t in), frequency (v), amplitude (A), and number of oscillations (n) were derived, and the dependence of concentration of the reacting species on these oscillatory parameters was interpreted on the basis of the Field-Koros-Noyes mechanism. 2009 Wiley Periodicals, Inc.
- Ganaie, Nadeem B.,Peerzada
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Read Online
- Regioselective reactions on a 1,3-disubstituted dihydroxymethyl or dicarboxyl hexahydropentalene skeleton
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Iodo-, bromo-, chloro-etherification and oxymercuration-demercuration of hexahydropentalene 1,3-dimethanol were regioselectively realized with formation of pentalenofurane compounds in good yields. The corresponding hexahydropentaleno diacid and its monoester react regioselectively with MCPBA to give two γ-lactones. Haloetherification of the diacid also regioselectively gives halogenolactones in good yield. A new method for synthesis of a bislactone was developed in better yield (79%) than that presented in the literature (58%).
- T?nase, Constantin I.,Dr?ghici, Constantin,Shova, Sergiu,Cojocaru, Ana,Maganu, Maria,Munteanu, Cristian V.A.,Cocu, Florea
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Read Online
- Induction period in the BrO3 -, Ce(III), H2SO4, oxalic acid and ketone oscillating reaction
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Contrary to what has been thought, systems classified as bromine- hydrolysis-controlled (BHC) show an induction period. In studies on the effect of a family of ketones upon this type of oscillators, it was found that an induction period appears in an interval of concentrations of the ketone, or in an interval of the value of the enolization constant. Simulations of the processes involved and a corresponding explanation are shown in this paper.
- Berenstein, Igal,Agreda, Jesus,Barragan, Daniel
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Read Online
- Fluorescent azasteroids through ultrasound assisted cycloaddition reactions
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We report here the synthesis and optical spectral properties of several new azasteroid derivatives. The formation of these compounds was explained based on the most probable mechanism. The luminescent heterocycles were synthesized by 1,3‐dipolar cycloaddition reactions between benzo[f]quinoline and methylpropiolate or dimethyl acetylenedicarboxylate (DMAD). A selective and efficient way for [3+2]‐dipolar cycloaddition of benzo[f]quinolinium ylides under ultrasound (US) irradiation (20 kHz processing frequency) is presented. We report substantially higher yields under US irradiation, whereas the solvent amounts required are at least three‐fold less compared to classical heating. The azasteroid derivatives are blue emitters with λmax of fluorescence around 430–450 nm. A certain influence of the azasteroid substituents concerning absorption and fluorescent properties was observed. Compounds anchored with a bulky pivaloyl group or without a C=O carbonyl group have shown increased fluorescence intensity.
- Mangalagiu, Ionel,Moldoveanu, Costel,Zbancioc, Gheorghita
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- Novel method for synthesizing 1-bromo-2,2-dimethoxypropane
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The invention belongs to the technical field of biomedical intermediates, and provides a novel method for synthesizing 1-bromo-2,2-dimethoxypropane, wherein the method comprises the following steps: S1, bromination reaction: dissolving acetone in dichloromethane, preheating to 65 DEG C, adding bromine, controlling the temperature at 65-75 DEG C, and carrying out a reaction for 11-13 h to obtain 1-bromoacetone; S2, carrying out an up-protection reaction: dissolving 1-bromoacetone in methanol, adding trimethyl orthoformate and concentrated hydrochloric acid, and carrying out a reaction for 2-3 hto obtain 1-bromo-2,2-dimethoxypropane. By means of the technical scheme, the problems that in the prior art, hazardous materials are used in a method for synthesizing 1-bromo-2,2-dimethoxypropane, the yield is low, and a product is difficult to purify are solved.
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Page/Page column 4-6
(2020/07/15)
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- Diastereoselective Synthesis of Z-Alkenyl Disulfides from α-Thiophosphorylated Ketones and Thiosulfonates
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We developed a simple and efficient method for the synthesis of functionalized unsymmetrical Z-alkenyl disulfides under mild conditions in moderate to good yields. The designed method is based on the reaction of α-thiophosphorylated carbonyl compounds with thiotosylates in the presence of a base. The developed method allows the preparation of unsymmetrical Z-alkenyl disulfides bearing additional hydroxy, carboxy, or ester functionalities. (Figure presented.).
- Musiejuk, Mateusz,Doroszuk, Justyna,J?drzejewski, Bartosz,Ortiz Nieto, Gregory,Marin Navarro, Marisol,Witt, Dariusz
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supporting information
p. 618 - 626
(2019/12/24)
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- Development of triazolothiadiazine derivatives as highly potent tubulin polymerization inhibitors: Structure-activity relationship, in vitro and in vivo study
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Based on our prior work, we reported the design, synthesis, and biological evaluation of fifty-two new triazolothiadiazine-based analogues of CA-4 and their preliminary structure-activity relationship. Among synthesized compounds, Iab was found to be the most potent derivative possessing IC50 values ranging from single-to double-digit nanomolar in vitro, and also exhibited excellent selectivity over the normal human embryonic kidney HEK-293 cells (IC50 > 100 μM). Further mechanistic studies revealed that Iab significantly blocked tubulin polymerization and disrupted the intracellular microtubule network of A549 cells. Moreover, Iab induced G2/M cell cycle arrest by regulation of p-cdc2 and cyclin B1 expressions, and caused cell apoptosis through up-regulating cleaved PARP and cleaved caspase-3 expressions, and down-regulating of Bcl-2. Importantly, in vivo, Iab effectively suppressed tumor growth of A549 lung cancers in a xenograft mouse model without obvious signs of toxicity, confirming its potential as a promising candidate for cancer treatment.
- Ma, Weifeng,Chen, Peng,Huo, Xiansen,Ma, Yufeng,Li, Yanhong,Diao, Pengcheng,Yang, Fang,Zheng, Shengquan,Hu, Mengjin,You, Wenwei,Zhao, Peiliang
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- METHOD OF CONTROLLING PLANTS
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The present invention provides a method of controlling plants comprising applying to the plants, or to the locus of the plants a composition comprising (A) a compound of formula (I) selected from the group consisting of: Formula(I), or an N-oxide or salt form thereof, and (B) one or more further herbicides.
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Page/Page column 29
(2018/02/28)
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- Genetic control of predominantly error-free replication through an acrolein-derived minor-groove DNA adduct
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Acrolein, anα,β-unsaturated aldehyde, is generated in vivo as the end product of lipid peroxidation and from metabolic oxidation of polyamines, and it is a ubiquitous environmental pollutant. The reaction of acrolein with the N2 of guanine in DNA leads to the formation of γ-hydroxy-1-N2-propano-2′ deoxyguanosine (γ-HOPdG), which can exist inDNAin a ring-closed or a ring-opened form. Here, we identified the translesion synthesis (TLS) DNA polymerases (Pols) that conduct replication through the permanently ring-opened reduced form of γ-HOPdG ((r) γ-HOPdG) and show that replication through this adduct is mediated via Rev1/Polη-, Poli/Polκ-, and Polθ- dependent pathways, respectively. Based on biochemical and structural studies, we propose a role for Rev1 and Poli in inserting a nucleotide (nt) opposite the adduct and for Polsη and κ in extending synthesis from the inserted nt in the respective TLS pathway. Based on genetic analyses and biochemical studies with Polθ, we infer a role for Polθ at both the nt insertion and extension steps of TLS. Whereas purified Rev1 and Polθ primarily incorporate a C opposite (r)γ-HOPdG, Poli incorporates a C or a T opposite the adduct; nevertheless, TLS mediated by the Poli-dependent pathway as well as by other pathways occurs in a predominantly error-free manner in human cells. We discuss the implications of these observations for the mechanisms that could affect the efficiency and fidelity of TLS Pols.
- Yoon, Jung-Hoon,Hodge, Richard P.,Hackfeld, Linda C.,Park, Jeseong,Choudhury, Jayati Roy,Prakash, Satya,Prakash, Louise
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p. 2949 - 2958
(2018/02/28)
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- HERBICIDAL PYRIDAZINONE COMPOUNDS
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The present invention relates to compounds of Formula (I), or an agronomically acceptable salt of said compounds wherein R1a, R1b, R2, X, A, Ra, Rb, Rc, Rd and m are as defined herein. The invention further relates to herbicidal compositions which comprise a compound of Formula (I), to their use for controlling weeds. The invention further relates to intermediate compounds used to produce compounds of Formula (I).
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Page/Page column 25
(2018/05/24)
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- One-Pot Sequential Bromination and Fluorination to Access 3-Fluoroimidazo[1,2-a]pyridines from Arylketones
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3-Fluoro-2-arylimidazo[1,2-a]pyridines were selectively synthesised in one-pot from acetophenones and 2-aminopyridines under mild conditions. The sequence of reactions involved bromination, condensation, and late-stage fluorination. Two halogenating reagents play key roles in the process. We found that tetrabutylammonium tribromide and SelectfluorTM gave excellent yields of the desired products in the one-pot sequential reaction.
- Udavant, Rohini N.,Yadav, Ashok R.,Shinde, Sandip S.
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p. 3432 - 3436
(2018/07/25)
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- Diversity-Orientated Stereoselective Synthesis through Pd-Catalyzed Switchable Decarboxylative C?N/C?S Bond Formation in Allylic Surrogates
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Switchable catalytic transformation of reactants can be a powerful approach towards diversity-orientated synthesis from easily available molecular synthons. Herein, an endogenous ligand-controlled, Pd-catalyzed allylic substitution allowing for either selective C?N or C?S bond formation using vinylethylene carbonates (VECs) and N-sulfonylhydrazones as coupling partners has been developed. This versatile methodology provides a facile, divergent route for the highly chemo- and stereoselective synthesis of functional allylic sulfones or sulfonohydrazides. The newly developed protocol features wide substrate scope (nearly 80 examples), broad functional group tolerance, and potential for the late-stage functionalization of bioactive compounds. The isolation and crystallographic analysis of a catalytically competent π-allyl Pd complex suggests that the pathway leading to the allylic products proceeds through a different manifold as previously proposed for the functionalization of VECs with nucleophiles.
- Deng, Lei,Kleij, Arjan W.,Yang, Weibo
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supporting information
p. 19156 - 19161
(2018/11/30)
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- Ethylene oxide derivative and preparation method and application thereof to medicine
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The invention relates to an ethylene oxide derivative and a preparation method and application thereof to medicine, in particular to a compound shown in the general formula (I) or a stereisomer, hydrate, metabolite, solvate, pharmaceutically acceptable salt, co-crystal or a prodrug of the compound, preparation methods of the chemicals, and application of medicine compositions of the chemicals and a medicine composition of the compound to medicine, especially application as EGFR target spot inhibitors. Please see the formula (I) in the description. Definitions of substituent groups in the formula (I) are the same as the definitions of the description.
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Paragraph 0190; 0191; 0192; 0193; 0194
(2017/08/25)
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- HERBICIDAL PYRIDAZINONE COMPOUNDS
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The present invention relates to compounds of Formula (I), or an agronomically acceptable salt of said compounds wherein A1, R1, Ra, Rb, Rc and Rd are as defined herein. The invention further relates to herbicidal compositions which comprise a compound of Formula (I), to intermediate compounds used to produce compounds of Formula (I), to processes for producing compounds of Formula (I) and to the use of compounds of Formula (I) for controlling weeds, in particular in crops of useful plants.
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Page/Page column 57
(2017/11/10)
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- The unexpected formation of a triselenide from 4-methyl-5-tri-n-butylstannyl-1,3-dithiol-2-one and selenium dioxide
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When attempting to apply a Riley oxidation to a stannylated precursor instead of the expected aldehyde an acyclic triselenide was obtained in which a Se3 chain replaces the nBu3Sn substituents of two precursors. The reaction was found to be fully reproducible. The product bearing the Se3 moiety and, hence, potentially possessing beneficial biological activity was analyzed comprehensively including X-ray structural characterization and 77Se NMR.
- Schindler, Claudia,Schulzke, Carola
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- Trisubstituted Pyridinylimidazoles as Potent Inhibitors of the Clinically Resistant L858R/T790M/C797S EGFR Mutant: Targeting of Both Hydrophobic Regions and the Phosphate Binding Site
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Inhibition of the epidermal growth factor receptor represents one of the most promising strategies in the treatment of lung cancer. Acquired resistance compromises the clinical efficacy of EGFR inhibitors during long-term treatment. The recently discovered EGFR-C797S mutation causes resistance against third-generation EGFR inhibitors. Here we present a rational approach based on extending the inhibition profile of a p38 MAP kinase inhibitor toward mutant EGFR inhibition. We used a privileged scaffold with proven cellular potency as well as in vivo efficacy and low toxicity. Guided by molecular modeling, we synthesized and studied the structure-activity relationship of 40 compounds against clinically relevant EGFR mutants. We successfully improved the cellular EGFR inhibition down to the low nanomolar range with covalently binding inhibitors against a gefitinib resistant T790M mutant cell line. We identified additional noncovalent interactions, which allowed us to develop metabolically stable inhibitors with high activities against the osimertinib resistant L858R/T790M/C797S mutant.
- Günther, Marcel,Lategahn, Jonas,Juchum, Michael,D?ring, Eva,Keul, Marina,Engel, Julian,Tumbrink, Hannah L.,Rauh, Daniel,Laufer, Stefan
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p. 5613 - 5637
(2017/07/22)
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- Synthesis of functionalized indolizines: Via gold(i)-catalyzed intramolecular hydroarylation/aromatization of pyrrole-ynes
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A gold-catalyzed intramolecular hydroarylation/aromatization of pyrrole-ynes has been developed. This method provides a concise and straightforward route to functionalized indolizines through the construction of the pyridine ring of indolizines and also allows elaboration of its pyrrole moiety with or without functional groups. In addition, a wide variety of functional groups, such as aryl, alkenyl, alkynyl, pyridyl or thienyl groups, can be easily incorporated into the pyridine unit of the indolizine products under mild conditions. The utility of the indolizine products was demonstrated by their efficient transformations into various C3-functionalized indolizine derivatives.
- Li, Xiangdong,Zhao, Jidong,Xie, Xin,Liu, Yuanhong
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p. 8119 - 8133
(2017/10/10)
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- Quinoline derivatives and their use
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The invention discloses a quinoline derivative and a usage thereof, a compound with a structure as shown in a formula (I) and or a pharmaceutically acceptable salt of the compound. The compound or the pharmaceutically acceptable salt thereof disclosed by the invention can be applied to the field of preparation of drugs for preventing or treating tumors.
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Paragraph 0227; 0228; 0229
(2017/03/14)
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- Calix[4]pyrroles with Shortest Possible Strap: Exclusively Selective toward Fluoride Ion
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Four new calix[4]pyrroles with the shortest possible strap so far through ortho-linking of the aromatic unit have been synthesized, including a naphthalene-derived fluorescent receptor. They show exclusive selectivity toward the fluoride ion as confirmed by 1H NMR, isothermal titration calorimetry, and fluorescence spectroscopic study. Anion affinity could also be modulated further via functionalization at the strap. Computational analysis displays calix[4]pyrroles binding to fluoride ion in a very unusual 1,3-alternate conformation where the anion resides on the opposite side of the strap.
- Samanta, Ritwik,Kumar, B. Sathish,Panda, Pradeepta K.
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supporting information
p. 4140 - 4143
(2015/09/15)
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- Synthesis of Multiple-Substituted Pyrroles via Gold(I)-Catalyzed Hydroamination/Cyclization Cascade
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A gold-catalyzed cascade hydroamination/cyclization reaction of α-amino ketones with alkynes to form substituted pyrroles has been developed. The method offers several advantages such as high regioselectivity with the tested cases, wide functional group tolerance, and easily accessible starting materials. The synthetic utility of the obtained pyrrole products was demonstrated by their efficient transformations to 2-vinylated pyrroles via gold-catalyzed intermolecular hydroarylation.
- Li, Xiangdong,Chen, Ming,Xie, Xin,Sun, Ning,Li, Shi,Liu, Yuanhong
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supporting information
p. 2984 - 2987
(2015/06/30)
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- Enantioselective organocatalytic michael/aldol sequence: Anticancer natural product (+)-trans-dihydrolycoricidine
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A total synthesis of the anticancer natural product (+)-trans- dihydrolycoricidine is reported from α-azidoacetone and cinnamaldehyde precursors. Key elements include an asymmetric organocatalytic sequence proceeding by a regiospecific secondary-amine-catalyzed synMichael addition followed by an intramolecular aldol reaction. The sequence results in the formation of an advanced intermediate, containing three stereogenic centers, in one step which and was converted into the title compound in eight steps.
- McNulty, James,Zepeda-Velazquez, Carlos
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supporting information
p. 8450 - 8454
(2014/08/18)
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- Bromination of enamines from tertiary amides using the petasis reagent: A convenient one-pot regioselective route to bromomethyl ketones
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An original one-pot synthesis of bromomethyl ketones is achived using the Petasis reagent (dimethyltitanocene) as a key for enamine generation. Several amides were used to test the limits of the procedure by changing either the alkyl chain R or the amino portion of the starting materials. The enamines generated in situ were allowed to react with bromine at low temperature followed by hydrolysis to yield bromomethyl ketones in excellent yields (85 to 95%). Mechanistic details and optimum conditions for the reaction are briefly discussed. The present approach offers several advantages such as regioselectivity in enamine formation, good yields, mild reaction conditions, and ease of experimentation.
- Kobeissi, Marwan,Cherry, Khalil,Jomaa, Wissam
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supporting information
p. 2955 - 2965
(2013/09/02)
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- Asymmetric hydrogenation of α- Or β-acyloxy α,β- unsaturated phosphonates catalyzed by a Rh(i) complex of monodentate phosphoramidite
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The Rh(i) complex of a monodentate phosphoramidite bearing a primary amine moiety (DpenPhos) has been disclosed to be highly efficient for the asymmetric hydrogenation of a variety of α- or β-acyloxy α,β- unsaturated phosphonates, providing the corresponding biologically important chiral α- or β-hydroxy phosphonic acid derivatives with excellent enantioselectivities (90->99% ee).
- Zhang, Jinzhu,Dong, Kaiwu,Wang, Zheng,Ding, Kuiling
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supporting information; scheme or table
p. 1598 - 1601
(2012/03/22)
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- Mepyramine-JNJ7777120-hybrid compounds show high affinity to hH 1R, but low affinity to hH4R
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In literature, a synergism between histamine H1 and H 4 receptor is discussed. Furthermore, it was shown, that the combined application of mepyramine, a H1 antagonist and JNJ7777120, a H 4 receptor ligand leads to a synergistic effect in the acute murine asthma model. Thus, the aim of this study was to develop new hybrid ligands, containing one H1 and one H4 pharmacophor, connected by an appropriate spacer, in order to address both, H1R and H 4R. Within this study, we synthesized nine hybrid compounds, which were pharmacologically characterized at hH1R and hH4R. The new compounds revealed (high) affinity to hH1R, but showed only low affinity to hH4R. Additionally, we performed molecular dynamic studies for some selected compounds at hH1R, in order to obtain information about the binding mode of these compounds on molecular level.
- Wagner, Eva,Wittmann, Hans-Joachim,Elz, Sigurd,Strasser, Andrea
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supporting information; experimental part
p. 6274 - 6280
(2011/11/29)
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- Synthesis of novel thiazolo[2,3-b]quinazolines by cyclization reaction of octahydroquinazoline-2-thiones with α-bromoketones
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Novel thiazolo[2,3-b]quinazolines were prepared by the cyclization reaction between octahydroquinazoline-2-thiones with α-bromoketones, which provides a readily accessible multifunctionalized quinazoline template for diversity-oriented synthesis. 2011 · Copyright by Walter de Gruyter.
- Quan, Zheng-Jun,Wei, Ying,Wang, Xi-Cun
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body text
p. 181 - 185
(2012/03/10)
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- Role of 2-oxo and 2-thioxo modifications on the proton affinity of histidine and fragmentation reactions of protonated histidine
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A combination of electrospray ionisation (ESI), multistage and high-resolution mass spectrometry experiments was used to compare the gas-phase chemistry of the amino acids histidine (1), 2-oxohistidine (2), and 2-thioxo-histidine (3). Collision-induced dissociation (CID) of all three different proton-bound heterodimers of these amino acids led to the relative gas-phase proton affinity order of: histidine >2-thioxo-histidine >2-oxo-histidine. Density functional theory (DFT) calculations confirm this order, with the lower proton affinities of the oxidised histidine derivatives arising from their ability to adopt the more stable keto/thioketo tautomeric forms. All protonated amino acids predominately fragment via the combined loss of H2O and CO to yield a1 ions. Protonated 2 and 3 also undergo other small molecule losses including NH3 and the imine HN=CHCO2H. The observed differences in the fragmentation pathways are rationalised through DFT calculations, which reveal that while modification of histidine via the introduction of the oxygen atom in 2 or the sulfur atom in 3 does not affect the barriers against the loss of H2+CO, barriers against the losses of NH3 and HN=CHCO2H are lowered relative to protonated histidine.
- Lam, Adrian K. Y.,Hutton, Craig A.,O'Hair, Richard A. J.
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experimental part
p. 2591 - 2604
(2011/12/14)
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- One-step synthesis of N-acetylcysteine and glutathione derivatives using the Ugi reaction
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Fully protected natural and unnatural N-acetylcysteine, dipeptide Cys-Gly, glutathione, and homoglutathione derivatives were synthesized by the Ugi four-component reaction using various benzylthio aldehydes and ketones as carbonyl building blocks. The scope and limitations of the method were investigated. Formation of imidazoline by-products in the Ugi reaction was discussed. 2,2,2-Trifluoroethanol was shown to be a superior reaction media than methanol in some reactions. Also, the 4-methyl-2,6,7-trioxabicyclo[2.2.2]octyl derivative (OBO-ester) of isocyanoacetic acid was shown to be superior to use than ethyl isocyanoacetate as a peptide synthesis precursor in cases when higher reactivity of an isocyanide is required.
- Zhdanko, Alexander G.,Gulevich, Anton V.,Nenajdenko, Valentine G.
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experimental part
p. 4692 - 4702
(2009/10/02)
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- Discovery of imidazo[1,2-a]pyridines as potent MCH1R antagonists
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A series of imidazo[1,2-a]pyridine derivatives was identified and evaluated for MCH1R binding and antagonistic activity. Introduction of a methyl substituent at the 3-position of imidazo[1,2-a]pyridine provided compounds with a significant improvement in MCH1R affinity. Representative compounds in this series exhibited good potency and brain exposure in rats.
- Kishino, Hiroyuki,Moriya, Minoru,Sakuraba, Shunji,Sakamoto, Toshihiro,Takahashi, Hidekazu,Suzuki, Takao,Moriya, Ryuichi,Ito, Masahiko,Iwaasa, Hisashi,Takenaga, Norihiro,Ishihara, Akane,Kanatani, Akio,Sato, Nagaaki,Fukami, Takehiro
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scheme or table
p. 4589 - 4593
(2010/04/25)
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- A convenient one-pot synthesis of thiazol-2-imines: application in the construction of pifithrin analogues
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For the first time a reaction intermediate has been isolated giving further insight into the mechanism of thiazol-2-imine formation. The first step of the reaction requires a basic medium, while the second step is an acid mediated E1 elimination reaction. An efficient one-pot synthesis of substituted thiazol-2-imines have been achieved by the condensation of carbonyl compounds with thioureas and 1,3-disubstituted thioureas using 1,1′-(ethane-1,2-diyl)dipyridinium bistribromide (EDPBT). Unsymmetrical 1,3-disubstituted thioureas give regioselective products with symmetrical ketones, which are mainly governed by the pKas of NH protons of thiourea, whereas symmetrical 1,3-disubstituted thioureas give regioselective products with symmetrical carbonyl compounds owing to the regioselective bromination of ketones. The methodology is extended to access novel neurodegenerative drug candidate pifithrin-α analogues in good yields in shorter reaction time. This method is simple, versatile and is applicable for different 1,3-disubstituted thioureas as well as a range of carbonyl compounds.
- Murru, Siva,Singh,Kavala, Veerababurao,Patel, Bhisma K.
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p. 1931 - 1942
(2008/09/17)
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- A new facile synthetic method for the construction of 1,3-oxathiolan-2-ylidenes
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A new, convenient and efficient synthetic method for the construction of 1,3-oxathiolan-2-ylidenes via sodium borohydride reduction of the addition product of dithiocarbamic acid esters with α-bromoketones under basic conditions is reported. This method is general and applicable to a range of systems.
- Ghosh, Harisadhan,Singh,Murru, Siva,Kavala, Veerababurao,Patel, Bhisma K.
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p. 2602 - 2606
(2008/09/18)
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- A general approach toward Janus diones: synthesis of dicyclopenta[b,g]naphthalene-1,3,6,8(2H,7H)-tetraone
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A general approach toward Janus diones involving the reaction of pyromellitic or naphthalenetetracarboxylic dianhydrides with ethyl(triphenylphosphoranylidene)acetate and subsequent rearrangement of the products is described. This approach allows avoiding the formation of poorly soluble intermediates, in which purity cannot be effectively controlled. Dicyclopenta[b,g]naphthalene-1,3,6,8(2H,7H)-tetraone 3, a promising precursor of molecular and polymeric advanced materials is described.
- Niebel, Claude,Lokshin, Vladimir,Khodorkovsky, Vladimir
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body text
p. 7276 - 7278
(2009/04/10)
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- Highly specific and broadly potent inhibitors of mammalian secreted phospholipases A2
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We report a series of inhibitors of secreted phospholipases A2 (sPLA2s) based on substituted indoles, 6,7-benzoindoles, and indolizines derived from LY315920, a well-known indole-based sPLA2 inhibitor. Using the human group X sPLA2 crystal structure, we prepared a highly potent and selective indole-based inhibitor of this enzyme. Also, we report human and mouse group IIA and IIE specific inhibitors and a substituted 6,7-benzoindole that inhibits nearly all human and mouse sPLA 2s in the low nanomolar range.
- Oslund, Rob C.,Cermak, Nathan,Gelb, Michael H.
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supporting information; experimental part
p. 4708 - 4714
(2009/06/06)
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- PROCESS FOR PREPARIING 1,3-DIBROMOACETONE, 1-3-DICHLOROACETONE AND EPICHLOROHYDRIN
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A process for preparing 1,3-dibromoacetone, 1-3-dichloroacetone and epichlorohydrin which comprises: (a) reacting acetone with 2 moles of bromine to make a mixture of brominated acetone derivatives and byproduct hydrogen bromide; (b) equilibrating the mixture of brominated acetone derivatives and hydrogen bromide to produce 1,3-dibromoacetone as the major product; (c) crystallizing the 1,3-dibromoacetone; and (d) isolating the 1,3-dibromoacetone. The process may further include the steps of (e) reacting the 1,3-dibromoacetone with a chloride source to produce 1,3-dichloroacetone; (f) hydrogenating the isolated 1,3-dichloroacetone to produce 1,3-dichlorohydrin; and (g) cyclizing the 1,3-dichlorohydrin with a base to produce epichlorohydrin.
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Page/Page column 10-11
(2008/06/13)
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- Method for preparing chiral diphosphines
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The invention concerns a method for preparing a compound of formula (1) wherein: A represents naphthyl or phenyl optionally substituted; and Ar1, Ar2independently represent a saturated or aromatic carbocyclic group, optionally substituted.
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- AZOLE METHYLIDENE CYANIDE DERIVATIVES AND THEIR USE AS PROTEIN KINASE MODULATORS
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The present invention is related to azole derivatives notably for use as pharmaceutically active compounds, as well as to pharmaceutical formulations containing such azole derivatives. Said azole derivatives are modulators of the protein kinase signalling pathways, particularly the one involving c-Jun N-terminal kinase and/or Glycogen Kinase Synthase 3. The present invention is furthermore related to novel azole derivatives as well as to methods of their preparation. X is O, S or NR0, with R0 being H or an unsubstituted or substituted C1 -C6 alkyl; A is 2-pyridyl, 3-pyridyl, 4-pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl or triazinyl group.
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- A mild, convenient, and inexpensive procedure for conversion of vinyl halides to α-haloketones
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Treatment of a vinyl chloride with commercially available aqueous sodium hypochlorite solution in a 2:5 mixture of acetic acid/acetone at 0 °C for about 1 h cleanly leads to the corresponding α-chloroketone. Similarly, if a vinyl bromide is exposed to sodium hypobromite (freshly prepared from bromine and sodium hydroxide) at 0 °C in 2:5 acetic acid/acetone as solvent, an α-bromoketone is produced. This methodology has been applied to a number of vinyl chlorides and vinyl bromides, and the transformations generally proceed in high yields. The mild reaction conditions are compatible with a variety of functional groups including amides, esters, and imines.
- VanBrunt, Michael P.,Ambenge, Reuben O.,Weinreb, Steven M.
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p. 3323 - 3326
(2007/10/03)
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- Nitroxyl compounds and drugs and reagents containing the same as the active ingredient
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Nitroxyl compounds represented by general formula (I) which are usable in acquiring information about active oxygen or in vivo free radicals as biological images such as magnetic resonance images or magnetoencephalograms, wherein A represents hydrogen or —L—(CH2)n—OCOR (wherein L represents —COO— or -alkylene-COO—; and R represents C1-4alkyl); R1, R2, R3, and R4represent each C1-4alkyl; and n is a number of from 1 to 4. Drugs and reagents containing the above compounds are usable in preventing, treating or diagnosing ischemic diseases, digestive diseases, cancer, cranial nervous diseases accompanied by nerve degeneration, inflammation, cataracts, or drug-induced organopathy.
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- Pyrrole derivatives and medicinal composition
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The invention relates to a pharmaceutical composition comprising a pyrrole derivative of the following formula [1] or a pharmaceutically acceptable salt thereof, or a solvate of either of them, as an active ingredient. STR1 (wherein R1 represents hydrogen or alkoxycar91 bonylamino, R2 represents alkyl, aryl which may be substituted, aromatic heterocyclyl which may be substituted, unsubstituted amino, monoalkylamino, dialkylamino, or cyclic amino which may be substituted; R3 represents cyano or carbamoyl; R4 represents hydrogen or alkyl; E represents alkylene; q is equal to 0 or 1, A represents methyl, aryl which may be substituted, or aromatic heterocyclyl which may be substituted). The pharmaceutical composition of the invention is effective for the treatment of pollakiuria or urinary incontinence.
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- Esterification of carboxylic acid salts
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Mono- or polycarboxylic acid esters are prepared by reacting a salt of such carboxylic acid with an organic halocompound, e.g., a (cyclo)alkyl, (cyclo)alkenyl, aryl or aralkyl halide, in an aqueous reaction medium, in the presence of a catalytically effective amount of a phase transfer catalyst, for example an onium salt.
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- Reaction of α-halo- and α,α-dihalo-β-oxoaldehydes with o- and m-phenylenediamines
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α-Halo-β-oxoaldehydes react with o- and m-phenylenediamines to give α-halo-β-oxoenamines. In the case of o-phenylenediamine, the initially formed monoenamine undergoes concurrent intramolecular cyclization to give benzimidazole and a halocarbonyl compound. α,α-Dihalo-β-oxoaldehydes react with o- and m-phenylenediamines according to the haloformic decomposition scheme involving formylation of amino groups.
- Guseinov,Klimentova,Yudina,Kol'tsova,Moskva
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p. 459 - 461
(2007/10/03)
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- SELECTIVE MONOBROMINATION OF KETONES BY BIS(DIMETHYLACETAMIDE)HYDROGEN TRIBROMIDE
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A unified procedure for the α-monobromination of ketones by bis(dimethylacetamide)hydrogen tribromide in methanol is proposed.Methyl aryl ketones with donating and moderately accepting substituents in the ring readily enter into the reaction. 1-Bromo ketones are mostly formed during the bromination of methyl alkyl ketones.
- Rodygin, M. Yu.,Mikhailov, V. A.,Savelova, V. A.
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p. 881 - 887
(2007/10/02)
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- Electron versus Hydride Ion Transfer in the Reduction of β-Halogen-Substituted 1,2-Dioxetanes by 1,4-Dihydronicotinamides
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The 3-halo-substituted 1,2-dioxetane 1 was employed as mechanistic probe in the reaction with NADH model compounds, namely, three N-substituted 1,4-dihydronicotinamides and 9,10-dihydro-10-methylacridine (AcrH2), to differentiate between the direct hydride ion transfer and the electron transfer (SET) mechanisms.While AcrH2 led mostly to cleavage into carbonyl products, the nicotinamide reduced the dioxetane 1 to yield the epoxy alcohol 3 as the main product.Additionally, the diol 2, the cleavage product bromoacetone, and the dehalogenation product acetone were observed.The formation of 3 is interpreted in terms of direct hydride ion transfer from the nicotinamides to the dioxetane with subsequent bromide elimination of the intermediary alkoxide.The dehalogenation product acetone was taken as evidence for initial electron transfer.
- Adam, Waldemar,Heil, Markus,Hutterer, Rudi
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p. 4491 - 4495
(2007/10/02)
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- HEXAHYDROBENZOTHIAZOLOPYRIDINIUM SALTS
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Salts of hexahydrobenzothiazolopyridine are obtained by exchange reactions.Anions are placed in the order - > ClO4- > I3- > Br- according to the ability to displace each other.X-ray structural and spectroscopic studies establish the cis-attachement of the thiazolidine and cyclohexane rings in the hexahydrobenzothiazolopyridinium salts studied.
- Shestopalov, A. M.,Nesterov, V. N.,Sharanin, Yu. A.,Litvinov, V. P.,Shklover, V. E.,et al.
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p. 1391 - 1397
(2007/10/02)
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- Oxybromination Catalysed by the Heteropolyanion Compound H5PMo10V2O40 in an Organic Medium: Selective para-Bromination of Phenol
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Selective bromination of phenol and its derivatives and the bromination of ketones and alkenes have been achieved by oxybromination at ambient conditions catalysed by the mixed addenda heteropolyanion compound H5PMo10V2O40, which is dissolved in a nonpolar chlorohydrocarbon solvent by complexation with tetraglyme.
- Neumann, Ronny,Assael, Igal
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p. 1285 - 1287
(2007/10/02)
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- Synthesis and Antifungal Activity of a Series of Novel 1,2-Disubstituted Propenones
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To find an antifungal agent other than those of the imidazole and triazole series, a new class of 1,2-disubstituted propenones I and II was prepared and tested for antifungal activity.Comparison of the structure-activity relationships showed that the conjugated structure of carbonyl and exomethylene groups in I and II plays an important role in potent antifungal acivity.However, it is noteworthy that compounds 53, 54, and 56, which have a hydroxymethyl or methoxymethyl group instead of an exo-methylene group in I, also showed potent activity.Although many compounds exhibited strong antifungal activity in vitro, none showed activity in vivo of oral efficacy against subacute systemic candidiasis in mice. '
- Ogata, Masaru,Matsumoto, Hiroshi,Kida, Shiro,Shimizu, Sumio,Tawara, Katsuya,Kawamura, Yoshimi
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p. 1497 - 1502
(2007/10/02)
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