Showing papers on "Morpholine published in 2012"
TL;DR: The synthesis and pharmacological activity of a new series of 1-aryl pyrazoles as potent σ1 receptor (σ1R) antagonists are reported in this paper. But the nature of the pyrazole substituents was crucial for activity, and a basic amine was shown to be necessary, in accordance with known receptor pharmacophores.
Abstract: The synthesis and pharmacological activity of a new series of 1-arylpyrazoles as potent σ1 receptor (σ1R) antagonists are reported. The new compounds were evaluated in vitro in human σ1R and guinea pig σ2 receptor (σ2R) binding assays. The nature of the pyrazole substituents was crucial for activity, and a basic amine was shown to be necessary, in accordance with known receptor pharmacophores. A wide variety of amines and spacer lengths between the amino and pyrazole groups were tolerated, but only the ethylenoxy spacer and small cyclic amines provided compounds with sufficient selectivity for σ1R vs σ2R. The most selective compounds were further profiled, and compound 28, 4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine (S1RA, E-52862), which showed high activity in the mouse capsaicin model of neurogenic pain, emerged as the most interesting candidate. In addition, compound 28 exerted dose-dependent antinociceptive effects in several neuropathic pain models. This, together with its...
114 citations
TL;DR: In this article, the reactivity of applied amine compounds in this ring-opening was tested by varying the structure of the amine compound and showed that steric hindrance at the reacting amine function plays a more prominent role than local point charge.
Abstract: Diols obtained by the ring-opening of biomass-based gamma-valerolactone (GVL) are potentially valuable building blocks that can be used as precursors in the manufacture of green polymers and resins. We report here a study on the ring-opening of GVL through adding amine compounds. The reactivity of the applied amine compounds in this ring-opening was tested by varying the structure of the amine compounds. Both mono-amines (ammonium, 2-aminoethanol, 2-phenylethylamine, and morpholine) and di-amines (1,2-diaminoethane, 1,2-diaminopropane, and piperazine) were used. The study showed that steric hindrance at the reacting amine-function plays a more prominent role than local point charge. To optimize the yield of the desired di-functional monomers, the ring-opening of GVL with 1,2-diaminoethane (1,2-DE) was studied in more detail. Reaction temperature (25-100 degrees C), reaction time, and molar ratio of the reactants appeared to be the determining processing parameters. These were found to be more important than the use of catalysts (triphenylphosphine, Tin(II)-2-ethylhexanoate, Ytterbium(III)trifuoromethanesulfonate, AlCl3, and SnCl2) and solvent polarity (methanol, DMA, DMSO, and water). (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 123: 3556-3564, 2012
73 citations
TL;DR: In this paper, the formation of carbamates of selected series of primary and secondary amines over the temperature range (288 to 318) K has been investigated by equilibrium 1H NMR studies, and the stability constants (K9) for the equilibrium: RNH 2 + HCO 3 - ⇄ K 9 RNHCOO - + H 2 O are reported.
70 citations
TL;DR: The overall suitability of an amine for PCC in terms of kinetics and energy is discussed and a Brønsted correlation relating the protonation constant of the amine to the carbamic acid formation rate and equilibrium constants at 25.0 °C has been established.
Abstract: The kinetics of the fast reversible carbamate formation reaction of CO2(aq) with a series of substituted cyclic secondary amines as well as the noncyclic secondary amine diethanolamine (DEA) has been investigated using the stopped-flow spectrophotometric technique at 25.0 °C. The kinetics of the slow parallel reversible reaction between HCO3– and amine has also been determined for a number of the amines by 1H NMR spectroscopy at 25.0 °C. The rate of the reversible reactions and the equilibrium constants for the formation of carbamic acid/carbamate from the reactions of CO2 and HCO3– with the amines are reported. In terms of the forward reaction of CO2(aq) with amine, the order with increasing rate constants is as follows: diethanolamine (DEA) < morpholine (MORP) ∼ thiomorpholine (TMORP) < N-methylpiperazine (N-MPIPZ) < 4-piperidinemethanol (4-PIPDM) ∼ piperidine (PIPD) < pyrrolidine (PYR). Both 2-piperidinemethanol (2-PIPDM) and 2-piperidineethanol (2-PIPDE) do not form carbamates. For the carbamate formi...
68 citations
TL;DR: Application of the reactivity trends established for [Pd(cinnamyl)Cl](2)/L1 toward the chemoselective synthesis of di-, tri-, and tetraamines was achieved.
Abstract: We report a diverse demonstration of synthetically useful chemoselectivity in the synthesis of di-, tri-, and tetraamines (62 examples) by use of Buchwald-Hartwig amination employing a single catalyst system ([Pd(cinnamyl)Cl](2)/L1; L1 = N-(2-(di(1-adamantyl)phosphino)phenyl)morpholine, Mor-DalPhos). Competition reactions established the following relative preference of this catalyst system for amine coupling partners: linear primary alkylamines and imines > unhindered electron-rich primary anilines, primary hydrazones, N,N-dialkylhydrazines, and cyclic primary alkylamines > unhindered electron-deficient primary anilines, α-branched acyclic primary alkylamines, hindered electron-rich primary anilines ≫ cyclic and acyclic secondary dialkylamines, secondary alkyl/aryl and diarylamines, α,α-branched primary alkylamines, and primary amides. The new isomeric ligand N-(4-(di(1-adamantyl)phosphino)phenyl)morpholine (p-Mor-DalPhos, L2) was prepared in 63% yield and was crystallographically characterized; the [Pd(cinnamyl)Cl](2)/L2 catalyst system exhibited divergent reactivity. Application of the reactivity trends established for [Pd(cinnamyl)Cl](2)/L1 toward the chemoselective synthesis of di-, tri-, and tetraamines was achieved. Preferential arylation was observed at the primary alkylamine position within 2-(4-aminophenyl)ethylamine with [Pd(cinnamyl)Cl](2)/L1 and 4-chlorotoluene (affording 5a); the alternative regioisomer (5a') was obtained when using [Pd(cinnamyl)Cl](2)/L2. These observations are in keeping with coordination chemistry studies, whereby binding of 2-(4-aminophenyl)ethylamine to the in situ generated [(L1)Pd(p-tolyl)](+) fragment occurred via the primary amine moiety, affording the crystallographically characterized adduct [(L1)Pd(p-tolyl)(NH(2)CH(2)CH(2)(4-C(6)H(4)NH(2))](+)OTf(-) (7) in 72% yield.
58 citations
TL;DR: This paper presents the structural features of ionic complexes formed by morpholine and metal ions which belong to group VA, namely Sb(III) and Bi(III), and attempts to show a relationship between the acentric symmetry of compounds and the type of anionic network within the R(2)MX(5)-subgroup of halogenoantimonates and halogenobismuthates.
Abstract: This paper presents the structural features of ionic complexes formed by morpholine and metal ions which belong to group VA, namely Sb(III) and Bi(III). A series of target inorganic–organic hybrid compounds of the general formula [NH2(C2H4)2O]2MX5 (where M = Sb, Bi; X = Cl, Br) has been synthesized by incorporating the organic component (morpholine) into the highly polarizable one-dimensional halogenoantimonate(III)/halogenobismuthate(III) chain network. Among the studied compounds, four were found to crystallize in the room temperature phase in the piezoelectric, orthorhombic space group P212121, Z = 4, the feature being confirmed by the powder second harmonic generation of light and piezoelectric measurements. Dielectric dispersion studies between 200 Hz and 2 MHz disclosed a relaxation process below room temperature well described by the Cole–Cole equation. Based on crystal structures available in Cambridge Structural Database (version 5.32, November 2010) we attempt to show a relationship between the acentric symmetry of compounds and the type of anionic network within the R2MX5-subgroup (where R denotes organic cation) of halogenoantimonates(III) and halogenobismuthates(III).
56 citations
TL;DR: Novel series of 1-substituted aminomethyl-3-[1-(4-isobutylphenyl)ethyl]-4-(3-aryl-4-sydnonylidene) amino-1,2,4-triazol-5-thiones showed promising anti-inflammatory and analgesic activity.
49 citations
TL;DR: In this article, the catalytically active cationic platinum(II) complexes with bi- or tridentate (pincer) functionalized NHC ligands were found to be catalytic active in the hydroamination of unactivated alkenes.
47 citations
Patent•
13 Mar 2012TL;DR: In this article, morpholine spirocyclic piperidine amide compounds useful as inhibitors of ion channels were described and provided pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.
Abstract: The invention relates to morpholine spirocyclic piperidine amide compounds useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.
43 citations
TL;DR: Overall, the addition of solubilizing and metabolically blocked outer rings did improve solubility and decrease protein binding as designed, however, the metabolic stability for compounds in this series was generally lower than desired.
42 citations
TL;DR: The Schiff base compounds 5a, 5b, 5c, 6a, 6b, and 6c are subjected to antimicrobial activity against six patojen bacteria and two yeast strains and interactions between these compounds and pBR322 plasmid DNA are presented by agarose gel electrophoresis.
TL;DR: Experimental results show that fluxes could be measured when diclofenac salts with aliphatic amines are released from a saturated aqueous solution and permeation coefficients were found higher when the counterion contains a ring; while hydroxy groups alone do not appear to play an important role, the ring could sustain permeation, disrupting the organized domains of the membrane.
Abstract: The following bases: monoethylamine (EtA), diethylamine (DEtA), triethylamine (TEtA), monoethanolamine (MEA), diethanolamine (DEA), triethanolamine (TEA), pyrrolidine (Py), piperidine (Pp), morpholine (M), piperazine (Pz) and their N-2-hydroxyethyl (HE) analogs were employed to prepare 14 diclofenac salts. The salts were re-crystallized from water in order to obtain forms that are stable in the presence of water. Vertical Franz-type cells with a diffusional surface area of 9.62 cm2 were used to study the permeation of these diclofenac salts from their saturated solutions through an internal pig ear membrane. The receptor compartments of the cells contained 100 mL of phosphate buffer (pH 7.4); a saturated solution (5 mL) of each salt was placed in the donor compartment, thermostated at 37 °C. Aliquots were withdrawn at predetermined time intervals over 8 h and then immediately analyzed by HPLC. Fluxes were determined by plotting the permeated amount, normalized for the membrane surface area versus time. Permeation coefficients were obtained dividing the flux values J by the concentration of the releasing phase—that is, water solubility of each salt. Experimental results show that fluxes could be measured when diclofenac salts with aliphatic amines are released from a saturated aqueous solution. Different chemical species (acid, anion, ion pairs) contribute to permeation of the anti-inflammatory agent even though ion-pairs could be hypothesized to operate to a greater extent. Permeation coefficients were found higher when the counterion contains a ring; while hydroxy groups alone do not appear to play an important role, the ring could sustain permeation, disrupting the organized domains of the membrane.
TL;DR: The SAPO-34 as discussed by the authors was synthesized by the combination of TEAOH and morpholine templates, and colloidal silica and silicic acid, as the silica source under hydrothermal conditions.
TL;DR: The structural investigations of the compounds were verified by elemental analyses, mass spectrometry, Fourier transform infrared, and DEPT, HSQC, HMBC, and (31)P NMR techniques, and gel electrophoresis data demonstrated that 2e, 3c, and 3e promoted the formation of DNA cleavage.
Abstract: The reactions of octachlorocyclotetraphosphazene, N4P4Cl8, with N2O2 donor-type aminopodands (1a, 1b, 1g, and 1h) afforded two kinds of derivatives, namely, spiro-ansa-spiro (sas) (2a, 2b, 2g, and 2h) and ansa-spiro-ansa (asa) (3a and 3b) phosphazenes. The partly substituted sas phosphazenes (2a and 2b) reacted with excess pyrrolidine and morpholine in tetrahydrofuran to produce the tetrapyrrolidino (2c and 2d) and morpholino (2e and 2f) derivatives. The reactions of the asa phosphazenes (3a and 3b) with excess pyrrolidine and morpholine produced gem-2-trans-6-dichloropyrrolidinophosphazenes (3c and 3d) and -morpholinophosphazenes (3e and 3f). However, the fully substituted products were not obtained in these solvents. In addition, the expected fully substituted compound was not obtained from the reaction of 3a with excess pyrrolidine by standard or microwave-assisted methods. The reaction of the long-chain starting compound (1g) with N4P4Cl8 gave sas (2g) and the interesting 2,6-ansa-spiro-bicyclo produc...
TL;DR: One-step conversion including intramolecular hydrogen bond decomposition, aerobic oxidation, and condensation from α-hydroxyketones and 1,2-diamines into quinoxalines is reported using FeCl3 and morpholine as cocatalysts as mentioned in this paper.
TL;DR: Among 13 kinds of metal oxides, ceria (CeO 2 ) shows the highest catalytic activity for one-pot selective synthesis of the secondary amide from 2-cyanopyridine and n -octylamine as a test reaction as mentioned in this paper.
Abstract: Among 13 kinds of metal oxides, ceria (CeO 2 ) shows the highest catalytic activity for one-pot selective synthesis of the secondary amide from 2-cyanopyridine and n -octylamine as a test reaction. CeO 2 acts as a reusable heterogeneous catalyst, and it is effective for the secondary amide formation from various nitriles and amines in high yields (73% to >99%). Pharmacologically important products such as heteroaromatic N-alky amides and morpholine amide are effectively synthesized, indicating that CeO 2 can be a practically useful catalyst. A proposed mechanism includes (1) hydration of nitrile to the primary amide and (2) transamidation of the primary amide with amine as the rate-limiting step. This reaction mechanism provides a reason why the present catalytic system gives high selectivity.
TL;DR: An efficient synthesis of 2,2,6-trisubstituted morpholine is described which involves a multicomponent process by simply mixing epichlorohydrin, N-bromosuccinimide, nosyl amide, and an olefin.
TL;DR: In this article, air-stable P,N-bidentate ligands with cyclic secondary amine moieties linked to the benzene rings of triphenylphosphine were designed and prepared for the selective synthesis of δ-lactone through the palladium-catalyzed telomerization of 1,3-butadiene with carbon dioxide.
TL;DR: In this article, a polymorphic form of the morpholine solvate and two co-crystals with lone pair heterocycles are presented, which are used to synthesize paracetamol, one of the most widely available analgesics.
Abstract: Paracetamol, one of the most widely available analgesics, is long known, but still a challenge for crystal engineers. Herein we discuss a new polymorphic form of the morpholine solvate and present two novel co-crystals with lone pair heterocycles.
TL;DR: Four compounds designed and synthesized 4-(2-arylpyrido[3',2':3,4]pyrrolo[1,2-f]triazin-4-yl)morpholine derivatives showed selectivity over 15 tested protein kinases and anti-proliferative activity at micromolar concentration against several cancer cell lines.
TL;DR: In this article, the graft copolymer was characterized by Fourier Transform Infrared Spectroscopy and Scanning Electron Microscopy and the highest graft graft percentage was 40.92%.
Patent•
31 Oct 2012
TL;DR: In this article, the desflurane bacteria amide compound compound bactericide (DES-BAC) was presented, and the active ingredients of the DESFLURANE BAC compound were desFLurane amide and (E, Z) - 4-[3- (4-chlorphenyl) 3-(3, 4-dimethoxy phenyl) acrylyl] morpholine.
Abstract: The invention provides a desflurane bacteria amide compound bactericide The active ingredients of the desflurane bacteria amide compound bactericide are desflurane bacteria amide and (E, Z) - 4-[3- (4-chlorphenyl) 3-(3, 4-dimethoxy phenyl) acrylyl] morpholine In the desflurane bacteria amide compound bactericide, 1-50% of desflurane bacteria amide is contained, and 1-45% of (E, Z) - 4-[3- (4-chlorphenyl) 3-(3, 4-dimethoxy phenyl) acrylyl] morpholine is contained The desflurane bacteria amide compound bactericide has the advantages of improvement on sterilizing effect and efficiency
TL;DR: The [PdCl2(L)] (1-2) (L = N-{2-(aryltelluro)ethyl}morpholine/piperidine) complexes have been synthesized and characterized by multi-nuclei NMR and single crystal X-ray crystallography as mentioned in this paper.
TL;DR: Two diastereoselective and straightforward protocols for the high-yielding synthesis of 2, 3-trans- and 2,3-cis-6-methoxy-3-substituted morpholine-2-carboxylic esters were realized in few steps.
Abstract: Two diastereoselective and straightforward protocols for the high-yielding synthesis of 2,3-trans- and 2,3-cis-6-methoxy-3-substituted morpholine-2-carboxylic esters were realized in few steps, through the condensation between 5,6-diethoxy-5,6-dimethyl-1,4-dioxan-2-one and an appropriate imine, which is the key reaction to control the C2–C3 relative stereochemistry, followed by a methanolysis/ring-closure tandem reaction sequence. In particular, 2,3-trans-morpholines derive from the R*,S*-product of the acid condensation of N-functionalized alkylimines with the silylketene acetal of the above lactone, whereas 2,3-cis-morpholines derive from the R*,R*-product of basic condensation of an N-tosylimines with the lactone.
TL;DR: Some new tridentate ONO and ONS Schiff base complexes of [NiL(amine)] determined by X-ray crystallography indicates that the complex has planar structure and has four coordinate in the solid state.
TL;DR: A review of advances in the synthesis of morpholin-3-ones and morpholin2-ones is presented in this paper, where strategies employing various ringexpansion reactions using smaller heterocyclic substrates or multicomponent reactions are described.
Abstract: This review covers advances in the synthesis of morpholin-3-ones and morpholin-2-ones. Besides the classical approaches for the preparation of both heterocycles that utilize intermolecular cyclizations of reactants or oxidation of morpholine and its derivatives, strategies employing various ring-expansion reactions using smaller heterocyclic substrates or multicomponent reactions are described. 1 Introduction 2 Synthesis of Morpholin-3-ones 2.1 By Formation of Two Bonds 2.2 By Formation of One Bond 2.3 By Introduction of Substituents 3 Synthesis of Morpholin-2-ones 3.1 By Formation of Two Bonds 3.2 By Formation of One Bond 3.3 By Introduction of Substituents 4 Conclusion
TL;DR: Asymmetric deprotonation of PMe2(t-Bu)(BH3) with s-BuLi/(−)-sparteine, followed by treatment with MeSiCl3, gave a 2.6:1 mixture of the C3- and C1-symmetric triphosphine-boranes MeSi(CH2PMe(t -Bu)3))3 (3) as mentioned in this paper.
TL;DR: In this paper, the authors used differential scanning calorimetry (DSC) and thermogravimetric (TG) to study the stability of asymmetrical and asymmetrical piperidyl and morpholinyl pigments.
Abstract: Crystalline structure, thermo-oxidative and thermal stability of symmetrical and asymmetrical piperidyl and morpholinyl derivatives of both N-substituted and non-N-substituted butyl diphenyl-diketo-pyrrolopyrrole (DPP) pigments were studied using differential scanning calorimetry (DSC) and thermogravimetry (TG). Except for the asymmetrical morpholine DPP derivative, all the samples showed melting peaks which were relatively close to their degradation temperatures (from 260 to 430 °C). Using DSC, monotropic polymorphism was revealed in the symmetrical piperidyl-N-butyl-derivative which confirmed earlier observation about tendency of symmetrical N-alkyl DPP derivates to form several crystalline structures. TG carried out under nitrogen atmosphere served for distinguishing of evaporation/sublimation and degradation temperatures. Temperatures of evaporation/sublimation were typically 10–30 °C lower in comparison with temperatures of thermal degradation. The highest thermal (450 °C) and thermo-oxidative stability (around 360 °C) showed the DPP derivatives containing morpholine moieties with no alkyl substitution on NH-group of DPP core. The presence of the latter was found to be the most destabilizing factor. Piperidyl group showed more stabilizing effect due to its polar character and its influence on π–π intermolecular interactions of neighbouring phenyl groups. The highest stabilizing effect of morpholine moiety on DPP structure was explained based on the presence of polar oxygen atom in that group. The preparations of 3,6-di-(4-morpholinophenyl)-2,5-dihydro-pyrrolo[3,4-c]pyrrole-1,4-dione and 3-(phenyl)-6-(4-morpholinophenyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione are reported.
TL;DR: The acyl-Claisen rearrangement of substituted phenylacetyl chlorides and cinnamyl morpholines gives 2,3-syn-diarylpent-4-enamides.
TL;DR: The 1H NMR and nuclear overhauser effect spectroscopy (NOESY) spectra of the dinuclear chelate ring complex (Pt2Cl2(Saf-1H)2) were analyzed in this paper.
Abstract: Reaction of the dinuclear chelate ring complex [Pt2Cl2(Saf-1H)2], Saf-1H: deprotonated safrole, with various amines afforded cis-[Pt(Saf-1H)(Am)Cl], Am: NH3 (1), Me2NH (2), Et2NH (3), morpholine (4), cyclohexylamine (5), benzylamine (6), aniline (7), o-toluidine (8), m-toluidine (9), p-toluidine (10), pyridine (11), 2-aminopyridine (12), and quinoline (13). The 1H NMR and nuclear overhauser effect spectroscopy (NOESY) spectra of the reported complexes were accurately analyzed. NOESY spectra show that the complexes have a cis-configuration, in which the alkyl and aryl groups of coordinated amines are in proximity to the allyl group of chelating safrole. Complexes 11, 12, and 13 exhibit inhibitory activities on human cancer cells HepG2 and Lu with IC50 = 2.5–5.0 µg mL−1.