- Novel quaternary ammonium functional addition-type norbornene copolymer as hydroxide-conductive and durable anion exchange membrane for direct methanol fuel cells
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Novel quaternary ammonium functional addition-type norbornene copolymers (QCnP(BN/PhBN), n = 1, 6, 10, 12) with different alkyl side chain length comb-shaped structures or different contents of 2-(4-phenyl-butoxymethy-lene)-5-norbornene (PhBN) (22-77%) are synthesized via copolymerization of functionalized norbornenes, and their corresponding hydroxide-conductive anion exchange membranes (AEMs) with effective hydrophilic-hydrophobic separation are prepared and confirmed by TEM or SEM. The achieved AEMs show high ion exchange capacity (1.83 mmol g-1), as well as low methanol permeability (1.97-20.4 × 10-7 cm2 s-1), which are lower than that of Nafion. The ionic conductivity increases with the operation temperature increasing and is observed up to 4.14 × 10-3 S cm-1. The AEMs exhibit excellent dimensional stability with a swelling degree in plane between 0.9-3.3% and good chemical stability under 6 M NaOH solution even after a month. Membrane electrode assembly (MEA) is fabricated by using the alkalized QC12P(BN/PhBN)-77 as the AEM and tested in an alkaline direct methanol fuel cell. The open circuit voltage (OVC) of 0.54 V and the maximum current density of 66 mW cm-2 are achieved at 80 °C, respectively.
- He, Xiaohui,Liu, Jingyin,Zhu, Hongyu,Zheng, Yan,Chen, Defu
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Read Online
- Microwave accelerated facile synthesis of fused polynuclear hydrocarbons in dry media by intramolecular Friedel-Crafts alkylation
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Fused polynuclear tetrahydro arenes are synthesised in a fast, simple, high yielding and regiospecific procedure by an intramolecular Friedel-Crafts alkylation in dry media under microwave irradiation of the corresponding 1-bromo-4-arylbutanes immobilised on silica. The observed reactivity is rationalised by molecular modelling studies which suggest the occurence of a concerted mechanism.
- Kurteva, Vanya B.,Santos, Antonio Gil,Afonso, Carlos A.M.
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Read Online
- Cs2CO3 promoted O-alkylation of alcohols for the preparation of mixed alkyl carbonates
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The presence of cesium carbonate and tetrabutylammonium iodide (TBAI) facilitated efficient O-alkylation of alcohols with alkyl halides, giving rise to the exclusive formation of mixed alkyl carbonates. The cesium effect was also examined comparatively with other alkali carbonates.
- Chu,Dueno,Kyung Woon Jung
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Read Online
- Nucleophilic substitution reactions of unbranched alkyl amines using triazine reagents
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Since amines are present in many organic, biological, and drug molecules, a strategy of synthesizing desired compounds by nucleophilic substitution reactions of these amines is very attractive. By using triazine reagents, we have found that nucleophilic substitution reactions of unbranched alkyl amines via morpholine derivatives are feasible. This method can be performed under milder reaction conditions than those in previously reported methods.
- Kitamura, Masanori,Kitaoka, Yuki,Fujita, Hikaru,Kunishima, Munetaka
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- Regiodivergent Conversion of Alkenes to Branched or Linear Alkylpyridines
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Herein we report a practical protocol for the visible-light-induced regiodivergent radical hydropyridylation of unactivated alkenes using pyridinium salts. This approach provides a unified synthetic platform to control the regioselectivity of the synthesis of linear or branched C4-alkylated pyridines. A remarkable selectivity switch from the anti-Markovnikov to the Markovnikov product can be achieved by the addition of tetrabutylammonium bromide. The versatility of this protocol is further demonstrated based on the late-stage functionalization in pharmaceuticals.
- Kim, Minseok,Shin, Sanghoon,Koo, Yejin,Jung, Sungwoo,Hong, Sungwoo
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supporting information
p. 708 - 713
(2022/01/20)
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- Preparation method for p-phenylbutoxybenzoic acid
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The invention provides a preparation method for p-phenylbutoxybenzoic acid, belonging to the field of organic synthesis. According to the invention, palladium-based catalytic coupling is adopted, andthe Grignard reaction and the Friedel-Craft reaction are avoided, thereby avoiding the production of blue-green copper ion wastewater and generation of a large amount of acidic wastewater due to usageof aluminum trichloride; the preparation method of the invention is friendly to environment, simple in synthesis route and high in the yield of each step; and halogeno-benzene is used for replacing more expensive phenylmagnesium bromide and used as a starting material, so the preparation cost of p-phenylbutoxybenzoic acid is lowered. The p-phenylbutoxybenzoic acid obtained in the invention has good crystal form, high purity and good solubility. The data of embodiments of the invention show that the total yield of p-phenylbutoxybenzoic acid prepared in the invention is 60% or above, and the HPLC purity of p-phenylbutoxybenzoic acid is 99.9% or above.
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- Synthesis method of intermediate 1-bromo-4-phenylbutane
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The invention discloses a synthesis method of intermediate 1-bromo-4-phenylbutane. According to the method, 4-phenyl butanol, hydrobromic acid, POM-C3N4, melamine, phosphorous acid, ammonia water andMoO3 are taken as main raw materials, wherein the mass ratio of the 4-phenyl butanol to the hydrobromic acid is equal to 5 to 22; the molar ratio of the phosphorous acid to the ammonia water to the MoO3 is equal to 10 to 21 to 20, and the mass ratio of the C3N4 to P2Mo5 is equal to 5 to 1. According to the synthesis process provided by the invention, the 4-phenyl butanol and the hydrobromic acid are enabled to be subjected to a bromination reaction in presence of the catalyst POM-C3N4 so as to obtain the 1-bromo-4-phenylbutane. The traditional method uses concentrated sulfuric acid for bromination, so that a very serious carbonization phenomenon is caused, and the yield of brominated products is very low; after the POM-C3N4 heteroacid catalyst is adopted, the reaction is mild under the condition of reflux, and the yield is high; the obtained product is high in purity and simpler in aftertreatment.
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Paragraph 0008; 0019; 0020; 0029
(2019/01/07)
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- Halogenation through Deoxygenation of Alcohols and Aldehydes
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An efficient reagent system, Ph3P/XCH2CH2X (X = Cl, Br, or I), was very effective for the deoxygenative halogenation (including fluorination) of alcohols (including tertiary alcohols) and aldehydes. The easily available 1,2-dihaloethanes were used as key reagents and halogen sources. The use of (EtO)3P instead of Ph3P could also realize deoxy-halogenation, allowing for a convenient purification process, as the byproduct (EtO)3Pa?O could be removed by aqueous washing. The mild reaction conditions, wide substrate scope, and wide availability of 1,2-dihaloethanes make this protocol attractive for the synthesis of halogenated compounds.
- Chen, Jia,Lin, Jin-Hong,Xiao, Ji-Chang
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supporting information
p. 3061 - 3064
(2018/05/28)
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- Substrate and Catalyst Effects in the Enantioselective Copper-Catalysed C–H Insertion Reactions of α-Diazo-β-oxo Sulfones
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Excellent enantioselectivities of up to 98 % ee are achieved by employing the copper-bis(oxazoline)-NaBARF catalyst system in the C–H insertion reactions of α-diazo-β-oxo sulfones. The influence of variation of the bis(oxazoline) ligand, copper salt, additive and substrate on both the efficiency and the enantioselectivities of these intramolecular C–H insertion reactions has been explored. Optimum enantioselectivities are achieved with phenyl and diphenyl ligands across the substrate series.
- Shiely, Amy E.,Clarke, Leslie-Ann,Flynn, Christopher J.,Buckley, Aoife M.,Ford, Alan,Lawrence, Simon E.,Maguire, Anita R.
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supporting information
p. 2277 - 2289
(2018/06/04)
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- Bent-core mesogens with an aromatic unit at the terminal position
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Bent-core liquid crystals with a naphthalene central unit and an aromatic ring at the terminal position of molecular tails were synthesised with the aim of enhancing nanosegregation. It was found that the length of the spacer between the rigid core and the terminal aromatic moiety had a profound influence on the liquid crystal polymorphism. The homologues with short spacers exhibited nematic and columnar phases, whereas the homologue with long spacers exhibited a tilted lamellar phase with a liquid-like in-plane order, indicating an unusual morphology of the densely packed toroidal objects. The morphology can be changed to twisted ribbons by small additives adsorbed on the membrane surface. This is the first example of twisted ribbons constructed by a lamellar system with no long-range in-plane order.
- Bajzíková, Kvetoslava,Svoboda, Ji?í,Novotná, Vladimíra,Pociecha, Damian,Gorecka, Ewa
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supporting information
p. 4672 - 4679
(2017/07/10)
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- P-phenylbutoxy benzoic acid and preparation method thereof
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The invention discloses a preparation method of p-phenylbutoxy benzoic acid. The preparation method comprises the following steps: by using 1,4-dibromobutane as a raw material, carrying out reaction on the 1,4-dibromobutane and benzene to obtain 4-phenylbromobutane; carrying out reaction on the 4-phenylbromobutane and methyl p-hydroxybenzoate to obtain methyl p-phenylbutoxy benzoate; and oxidizing the methyl p-phenylbutoxy benzoate, and meanwhile, carrying out hydrolysis to obtain the pranlukast intermediate p-phenylbutoxy benzoic acid. The p-phenylbutoxy benzoic acid prepared by the method has the advantages of high purity and high yield; and the method has the advantages of cheap and accessible raw materials, mild preparation conditions, high controllability and low production cost.
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Paragraph 0022
(2017/07/12)
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- Catalytic Access to Alkyl Bromides, Chlorides and Iodides via Visible Light-Promoted Decarboxylative Halogenation
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Herein is reported the catalytic, visible light-promoted, decarboxylative halogenation (bromination, chlorination, and iodination) of aliphatic carboxylic acids. This operationally-simple reaction tolerates a range of functional groups, proceeds at room temperature, and is redox neutral. By employing an iridium photocatalyst in concert with a halogen atom source, the use of stoichiometric metals such as silver, mercury, thallium, and lead can be circumvented. This reaction grants access to valuable synthetic building blocks from the large pool of cheap, readily available carboxylic acids.
- Candish, Lisa,Standley, Eric A.,Gómez-Suárez, Adrián,Mukherjee, Satobhisha,Glorius, Frank
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supporting information
p. 9971 - 9974
(2016/07/19)
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- Palladium-Catalyzed, Ring-Forming Aromatic C-H Alkylations with Unactivated Alkyl Halides
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A catalytic C-H alkylation using unactivated alkyl halides and a variety of arenes and heteroarenes is described. This ring-forming process is successful with a variety of unactivated primary and secondary alkyl halides, including those with β-hydrogens. In contrast to standard polar or radical cyclizations of aromatic systems, electronic activation of the substrate is not required. The mild, catalytic reaction conditions are highly functional group tolerant and facilitate access to a diverse range of synthetically and medicinally important carbocyclic and heterocyclic systems.
- Venning, Alexander R. O.,Bohan, Patrick T.,Alexanian, Erik J.
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supporting information
p. 3731 - 3734
(2015/04/14)
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- Rasta resin-triphenylphosphine oxides and their use as recyclable heterogeneous reagent precursors in halogenation reactions
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Heterogeneous polymer-supported triphenylphosphine oxides based on the rasta resin architecture have been synthesized, and applied as reagent precursors in a wide range of halogenation reactions. The rasta resin-triphenylphosphine oxides were reacted with either oxalyl chloride or oxalyl bromide to form the corresponding halophosphonium salts, and these in turn were reacted with alcohols, aldehydes, aziridines and epoxides to form halogenated products in high yields after simple purification. The polymersupported triphenylphosphine oxides formed as a byproduct during these reactions could be recovered and reused numerous times with no appreciable decrease in reactivity.
- Xia, Xuanshu,Toy, Patrick H.
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supporting information
p. 1397 - 1405
(2014/07/22)
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- Enantioselective copper catalysed C-H insertion reaction of 2-sulfonyl-2-diazoacetamides to form γ-lactams
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The first examples of asymmetric copper-catalysed intramolecular C-H insertion reactions of 2-sulfonyl-2-diazoacetamides are described; trans γ-lactams with up to 82% ee are achieved with the CuCl2-bisoxazoline-NaBARF catalyst system. The reactions generally display high efficiency and high trans selectivity, and also a strong regiochemical preference for insertion to lead to the formation of 5-membered rings over 4-membered rings. In cases where there are competing C-H insertion pathways available, to form sulfolanes or thiopyrans, only the insertion into the amide chain to form γ-lactams is observed. With phenylsulfonyl derivatives, a minor competing C-H insertion pathway leading to β-lactams is seen; interestingly, changing the identity of the copper ligand changes the product ratio of β/γ-lactams. The copper catalysed reactions compare favorably in terms of efficiency and enantioselectivity to the corresponding reactions catalysed by commercially available chiral rhodium catalysts.
- Clarke, Leslie Ann,Ring, Aoife,Ford, Alan,Sinha, Abhijeet S.,Lawrence, Simon E.,Maguire, Anita R.
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p. 7612 - 7628
(2015/02/18)
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- Indium(III)-catalyzed one-pot synthesis of alkyl cyanides from carboxylic Acids
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The one-pot preparation of alkyl cyanides from carboxylic acids via alkyl iodides or alkyl bromides, which were in situ generated either by indium(III)-catalyzed reductive iodination or bromination of carboxylic acids, is described. Georg Thieme Verlag Stuttgart New York.
- Moriya, Toshimitsu,Shoji, Kohei,Yoneda, Shinichiro,Ikeda, Reiko,Konakahara, Takeo,Sakai, Norio
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p. 3233 - 3238
(2013/12/04)
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- Indium-catalyzed reductive bromination of carboxylic acids leading to alkyl bromides
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The combination of 1,1,3,3-tetramethyldisiloxane (TMDS) and trimethylbromosilane (Me3SiBr) with a catalytic amount of indium bromide (InBr3) undertook direct bromination of carboxylic acids, which produced the corresponding alkyl bromides in good to excellent yields. The reducing system was tolerant to several functional groups.
- Moriya, Toshimitsu,Yoneda, Shinichiro,Kawana, Keita,Ikeda, Reiko,Konakahara, Takeo,Sakai, Norio
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supporting information
p. 4842 - 4845,4
(2020/09/16)
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- The application of a monolithic triphenylphosphine reagent for conducting Appel reactions in flow microreactors
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Herein we describe the application of a monolithic triphenylphosphine reagent to the Appel reaction in flow-chemistry processi to generate various brominated products with high purity and in excellent yields, and with no requirement for further off-line pu fication.
- Roper, Kimberley A.,Lange, Heiko,Polyzos, Anastasios,Berry, Malcolm B.,Baxendale, Ian R.,Ley, Steven V.
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supporting information; experimental part
p. 1648 - 1655
(2012/02/04)
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- Novel preparation of ion-supported triphenylphosphines and their synthetic utility
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Novel ion-supported Ph3P compounds, 4-(diphenylphosphino)- benzyltrimethylammonium bromide (A) and N-methyl-N-[4-(diphenylphosphino) -benzyl]pyrrolidinium bromide (B), were prepared. Because of their stability in air, ion-supported Ph3P A and B could be used for the halogenation of alcohols, the esterification of carboxylic acid with the Mitsunobu reaction, the Mizoroki-Heck reaction, and the Sonogashira reaction. The advantages of using these ion-supported Ph3P A and B are the simple isolation of the products by ether extraction due to their poor solubility in ether, and the easy recovery of the co-product, ion-supported Ph3PO, by filtration in high yields (>90%), which could be regenerated and reused for the same reactions, in the halogenation of alcohols and the esterification of carboxylic acid with the Mitsunobu reaction. On the other hand, ionic liquid reaction media containing Pd(OAc)2 or PdCl2 and ion-supported Ph3P A or B as catalysts could be reused for the same Mizoroki-Heck reaction and the Sonogashira reaction maintaining high yields, using iodotoluene with methyl acrylate and phenylacetylene, respectively.
- Imura, Yumi,Shimojuh, Naoya,Kawano, Yuhta,Togo, Hideo
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scheme or table
p. 3421 - 3426
(2010/06/19)
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- One-carbon extrusion from a tetraazafulvalene. Isolation of aldehydes and a study of their origin
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Reaction of imidazolylidene-derived enetetramine 2 with aliphatic iodides and bromides (and with aryl iodides bearing alkene-containing side-chains in the ortho-position) leads to formation of aliphatic aldehydes through an unprecedented extrusion of a one-carbon unit from the enetetramine. An intermediate 2-alkylimidazoline 24 is proposed, where the alkyl group derives from the substrate; this imidazoline undergoes further reaction in situ to afford the observed aldehydes on acidic workup. Modifiedsubstrates were designed and prepared to probe the chemistry of the alk ylimidazoline adducts and provided extensive information on the chemistry of the adducts.
- Murphy, John A.,Schoenebeck, Franziska,Findlay, Neil J.,Thomson, Douglas W.,Zhou, Sheng-ze,Garnier, Jean
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supporting information; experimental part
p. 6475 - 6479
(2009/09/26)
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- TRICYCLIC INHIBITORS OF FATTY ACID AMIDE HYDROLASE
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A series of substituted oxazole compounds having an alpha keto side chain at the 2 position and an aromatic, heteroaromatic or heterocycle substituent at the 5 position are disclosed. These compounds exhibit inhibition of fatty acid amid hydrolase and are useful for treatment of malconditions involving that enzyme.
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Page/Page column 84
(2009/01/24)
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- Structure-activity relationships of α-ketooxazole inhibitors of fatty acid amide hydrolase
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A systematic study of the structure-activity relationships of 2b (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed targeting the C2 acyl side chain. A series of aryl replacements or substituents for the terminal phenyl group provided effective inhibitors (e.g., 5c, aryl = 1-napthyl, K, - 2.6 nM), with 5hh (aryl -3-ClPh, Ki = 900 pM) being 5-fold more potent than 2b. Conformationally restricted C2 side chains were examined, and many provided exceptionally potent inhibitors, of which 11j (ethylbiphenyl side chain) was established to be a 750 pM inhibitor. A systematic series of heteroatoms (O, NMe, S), electron-withdrawing groups (SO, SO2), and amides positioned within and hydroxyl substitutions on the linking side chain were investigated, which typically led to a loss in potency. The most tolerant positions provided effective inhibitors (12p, 6-position S, Ki = 3 nM, or 13d, 2-position OH, Ki = 8 nM) comparable in potency to 2b. Proteome-wide screening of selected inhibitors from the systematic series of >100 candidates prepared revealed that they are selective for FAAH over all other mammalian serine proteases.
- Hardouin, Christophe,Kelso, Michael J.,Romero, F. Anthony,Rayl, Thomas J.,Leung, Donmienne,Hwang, Inkyu,Cravatt, Benjamin F.,Boger, Dale L.
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p. 3359 - 3368
(2008/02/13)
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- Dangling arms: A tetrahedral supramolecular host with partially encapsulated guests
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A protruding tail: A guest composed of a cationic sandwich complex, an alkyl chain, and a sulfonate anionic group is partially incorporated within a host [Ga4L6]12- cluster (see scheme). The cationic head group is quickly incorporated into the cavity of the host, while the sulfonate unit at the other end of the chain is not, as the alkyl sulfonate tail protrudes through an opening in a triangular face of the tetrahedral cluster. (Figure Presented).
- Tiedemann, Bryan E. F.,Raymond, Kenneth N.
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- Synthesis of N-glyoxyl prolyl and pipecolyl amides and thioesters and evaluation of their in vitro and in vivo nerve regenerative effects
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The recent discovery that small molecule ligands for the peptidyl-prolyl isomerase (PPIase) FKBP12 possess powerful neuroprotective and neuroregenerative properties in vitro and in vivo suggests therapeutic utility for such compounds in neurodegenerative disease. The neurotrophic effects of these compounds are independent of the immunosuppressive pathways by which drugs such as FK506 and rapamycin operate. Previous work by ourselves and other groups exploring the structure-activity relationships (SAR) of small molecules that mimic only the FKBP binding domain portion of FK506 has focused on esters of proline and pipecolic acid. We have explored amide and thioester analogues of these earlier structures and found that they too are extremely potent in promoting recovery of lesioned dopaminergic pathways in a mouse model of Parkinson's disease. Several compounds were shown to be highly effective upon oral administration after lesioning of the dopaminergic pathway, providing further evidence of the potential clinical utility of a variety of structural classes of FKBP12 ligands.
- Hamilton, Gregory S.,Wu, Yong-Qian,Limburg, David C.,Wilkinson, Douglas E.,Vaal, Mark J.,Li, Jia-He,Thomas, Christine,Huang, Wei,Sauer, Hansjorg,Ross, Douglas T.,Soni, Raj,Chen, Yi,Guo, Hongshi,Howorth, Pamela,Valentine, Heather,Liang, Shi,Spicer, Dawn,Fuller, Mike,Steiner, Joseph P.
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p. 3549 - 3557
(2007/10/03)
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- Synthesis of the β2 Agonist (R)-Salmeterol Using a Sequence of Supported Reagents and Scavenging Agents
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(Matrix Presented) The enantioselective synthesis of (R)-salmeterol has been achieved by using a sequence of supported reagents and sequestering agents. The saligenin core was installed by a regiospecific alkylation and a chiral auxiliary approach was employed to introduce the desired stereochemistry via a diastereoselective reduction.
- Bream, Robert N.,Ley, Steven V.,Procopiou, Panayiotis A.
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p. 3793 - 3796
(2007/10/03)
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- 2,3,5-substituted biphenyls useful in the treatment of insulin resistance and hyperglycemia
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This invention provides compounds of Formula I having the structure wherein:B, C, D, and R1 are as defined hereinbefore in the specification, or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.
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- Pyrrolidine modulators of chemokine receptor activity
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The present invention is directed to pyrrolidine compounds of the formula I: (wherein R1, R2, R3, R4, R5, R6, R14and n are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.
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- Imidazo heterocyclic compounds
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A novel class of imidazo heterocyclic compounds, pharmaceutical compositions comprising them and use thereof in the treatment and/or prevention of diseases and disorders related to the histamine H3 receptor. More particularly, the compounds are useful for the treatment and/or prevention of diseases and disorders in which an interaction with the histamine H3 receptor is beneficial.
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- Palladium-imidazolium carbene catalyzed aryl, vinyl, and alkyl Suzuki-Miyaura cross coupling.
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[reaction--see text] N,N-Bis-(2,6-diisopropylphenyl)dihydroimidazolium chloride with palladium(II) acetate (2 mol %) was used as catalyst, without added base, to efficiently cross couple aryl, vinyl, and alkyl boronates and boronic acids with aryldiazonium tetrafluoroborate substrates. The reactions were performed at 0 degrees C or rt, giving product in 2 to 4 h with 80 to 90% yields for isolated materials. Diazonium ions, formed in situ, also cross couple under these conditions.
- Andrus,Song
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p. 3761 - 3764
(2007/10/03)
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- Process for producing 1-bromo-4-phenylbutane
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A process for producing 1-bromo-4-phenylbutane of the formula (1): which is characterized by the steps of; reacting 4-bromobutyryl halide of the formula (2): where X is a halogen atom, with benzene in the presence of a Lewis acid to give a 4-bromobutyrophenone of the formula (3): and reacting 4-bromobutyrophenone compound of the formula (3) with hydrogen in the presence of a metal catalyst.
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- Efficient synthesis of β-amino bromides
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β-Aminoalcohols were smoothly converted to β-amino bromides using thionyl bromide and DMF, which were easily isolated without any further purification. Participation by the β-amino group in brominations not only enhanced reaction rates but also promoted stereo- and regioselectivities. (C) 2000 Elsevier Science Ltd.
- Nagle, Advait S.,Salvatore, Ralph N.,Chong, Byong-Don,Woon Jung, Kyung
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p. 3011 - 3014
(2007/10/03)
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- Structure-activity relationship for a series of 2-substituted 1,2,3,4- tetrahydro-9H-pyrido[3,4-b]indoles: Potent subtype-selective inhibitors of N- methyl-D-aspartate (NMDA) receptors
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A series of 2-substituted 1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indoles was synthesized as potential antagonists for the NR1(A)/2B subtype of N-methyl- D-aspartate (NMDA) receptors. Assayed by electrical recording under steady- state conditions, 7-hydroxy-2-(4-phenylbutyl)-1,2,3,4-tetrahydropyrido-[3,4- b]indole (30) was the most potent compound in the series having an IC50 value of 50 nM at the NR1(A)/2B receptors.
- Tamiz, Amir P.,Whittemore, Edward R.,Woodward, Richard M.,Upasani, Ravindra B.,Keana, John F.W.
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p. 1619 - 1624
(2007/10/03)
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- N-substituted imidazol derivative
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The present invention is to provide novel imidazole derivatives effectual as an antihyperlipemic agent and therapeutic and preventive drugs for arteriosclerosis, and to provide methods for manufacturing the said derivatives. More particularly, the present invention is directed to the compounds represented by the following general formula [I]; STR1 wherein R1 is hydrogen or lower alkyl, n is 0 or 1, X is N-r1 wherein r1 is hydrogen or lower alkyl, O, S, SO, SO2, CH2, CH(CH3), CONH or C(r2)=NO wherein r2 is hydrogen or lower alkyl, m is 0 or an integer of from 1 to 12, and A is methyl or a group represented by the following general formula; STR2 wherein Y is N-r3 wherein r3 is hydrogen or lower alkyl, N(r4)SO2 wherein r4 is hydrogen or lower alkyl, O, S, SO, SO2, CH2, CH(CH3), CONH or C(r5)=NO wherein r5 is hydrogen or lower alkyl, R2 is a halogen, a lower alkyl, a lower alkoxy, a cycloalkyl or COOr6 wherein r6 is hydrogen or a lower alkyl, and l is 0, 1, 2 or 3, however, m denotes an integer of from 6 to 9 when A is methyl, or m denotes 0 or an integer of from 1 to 6 when A is a group represented by the following general formula; STR3 and X and Y are each independently CH2 when m is 0, the pharmaceutically-acceptable salts thereof and methods for manufacturing the said compounds and the pharmaceutically-acceptable salts thereof.
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- Aryl acetylenes as mechanism-based inhibitors of cytochrome P450- dependent monooxygenase enzymes
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Aryl acetylenes have been investigated as inhibitors of cytochrome P450 (P450)-dependent alkoxyresorufin dealkylation activities in liver microsomes prepared from rats exposed to β-naphthoflavone, isosafrole, or phenobarbital. Many of the acetylenes investigated produce pseudo-first- order time-dependent and NADPH-dependent losses of the dealkylation activities characteristic of mechanism-based irreversible inactivation (suicide inhibition). Replacing the terminal hydrogen of aryl acetylenes with a methyl group to convert ethynes into propynes enhances the inhibition of P450 1A enzymes; in some instances, this modification converts a reversible inhibitor of P450s into a suicide inhibitor. In contrast, ethynes are more effective suicide inhibitors of P450 2B-dependent dealkylations than the corresponding propynes. Aryl acetylenes with an ethynyl group on the 2 position of naphthalene or on the 9 position of phenanthrene and arylalkyl acetylenes with alkyl chains containing 2, 3, or 4 methylene groups are selective inhibitors of P450 2B1/2B2 in liver microsomes from rats. Aryl acetylenes also act as suicide inhibitors of P450 1A2 in human liver microsomes, of purified P450 1A2 from rabbit or rat liver in reconstituted systems, and of purified recombinant human P450 1A2 and 1A1 in reconstituted systems. 4-(1-Propynyl)biphenyl (4PBi) inactivated P450 1A2-dependent ethoxyresourfin deethylation (EROD) activity in human liver microsomes in an NADPH-dependent process (k(inactivation), 0.23 min-1; K1, 2.3 μM). 4PBi also inactivated purified recombinant human P450 1A2 (k(inactivation), 0.24 min-1; K(I), 4.3 μM). In agreement with previous reports [Yun, C.-H., Hammons, G. J., Jones, G., Martin, M. V., Hopkins, N. E., Alworth, W. L., and Guengerich, F. P. (1992) Biochemistry 31, 10556-10563], 2-ethyny]naphthalene (2EN) was not a suicide inhibitor of the P450 1A2 activity in human liver microsomes but did inactivate purified human P450 1A2. Neither 4PBi nor 2EN affected diagnostic activities of human microsomal P450 2E1, 2C9/10, 3A4, or 2C19. In the systems examined, the losses of P450-dependent activity produced by these aryl acetylenes were not accompanied by corresponding decreases in the measured P450 absorption spectra. Thus P450 inactivation by these aryl acetylenes does not involve labeling and destruction of the heme. Incubation of 4PBi with microsomal P450 1A1 or 1A2 from rat liver under conditions that lead to P450-dependent enzyme inactivations generates a 2-biphenylylpropionic acid product. This suggests that the suicide inhibition of P450s by propynylaryl acetylenes proceeds via a methylaryl ketene formed by a 1,2- methyl rearrangement, analogous to the mechanism of suicide inhibition by ethynyl acetylenes that proceed via ketene intermediates formed by 1,2- hydrogen shifts [Ortiz de Montellano, P. R., and Kunze, K. L. (1981) Arch. Biochem. Biophys. 209, 710-712].
- Foroozesh, Maryam,Primrose, Ginny,Guo, Zuyu,Bell, L. Chastine,Alworth, William L.,Guengerich, F. Peter
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- Synthesis of long chain ω-aralkylbromides
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1-Iodo-4-acetoxybutane is a useful 4 carbon synthon which reacts selectively with Grignards under copper catalysis. The immediate products are converted to bromides.
- Forth,Smith
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p. 951 - 959
(2007/10/02)
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- Quaternary ammonium compounds having muscle relaxation activity
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A quaternary ammonium having a muscle relaxation activity compound represented by the formula (I): STR1 wherein R1 represents a methylene, a lower alkylenoxy, a lower alkenylene, a lower alkynylene, --CO--, --COO--, a lower alkylene carbonyloxy, --CH(OR5)--, a lower alkylenecarbonyl, a hydroxy lower alkylene, --O--, --S--, --SO--, or --SO2 --; R2 represents a hydrogen atom, a hydroxy lower alkyl, an aldehyde, a lower alkyl carbonyl, --NO2, or --NHR6 ; R3 represents a hydrogen atom of a group --R1 --(CH2)a --[CH(CH2 A)--CH2 ]b --A; R4 represents an anion; R5 and R6 represent a hydrogen atom or a acetyl; A represents a quaternary ammonium group; a represents an integer of 1 to 8; b represents 0 or 1; m represents an integer of 1 to 4; and (Z) represents a trivalent benzene ring, a trivalent naphthalene ring, a trivalent diphenyl or a trivalent ethane radical.
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- Alkenoic acid derivatives
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An alkenoic acid derivative of the formula STR1 in which X and Y are identical or different and represent sulfur, sulfoxide, sulfone, an alkylene chain, --SCH2 --, or oxygen or a direct bond, W represents --CH=CH-- or --CH2 --CH2 --, o represents a number 1 to 5, A and B are identical or different and represent carboxyl, carboxymethylene, tetrazolyl or tetrazolylmethylene, or --CO2 R9 or --CH2 CO2 R9 or --CONR10 R11 or nitrile n represents a number 1 to 10, m represents a number 0 to 7, T and Z are identical or different and represent oxygen or a direct bond and R2, R3, R8 are identical or different and represent hydrogen, alkyl, alkoxy, halogen, trifluoromethyl, trifluoromethoxy, cyano or nitro and R9 is lower alkyl and R10 and R11 are hydrogen, lower alkyl, alkylsulfonyl or arylsulfonyl or together are an alkylene chain to form a ring and pharmaceutically acceptable salts thereof. Such alkenoic acid derivatives are useful as leucotriene disease antagonists.
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- The Copper Halide-Catalyzed Mono-Substitution of Bromine in α,ω-Dibromoalkanes by Grignard Reagents. A Reinvestigation
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α,ω-Dibromoalkanes have been converted into mono-bromides R(CH2)nBr by reaction with the Grignard compounds RMgBr in THF in the presence of 5 mol percent of copper(I)bromide.In contrast to what is suggested in the original literature, this method has a limited scope.
- Andringa, H.,Hanekamp, J.,Brandsma, L.
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p. 2349 - 2351
(2007/10/02)
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- PHOTOCHEMICAL TRANSFORMATIONS - V ORGANIC IODIDES (Part 4) : SOLUTION PHOTOCHEMISTRY OF 4-PHENYL-1-IODOBUTANE AND 4-PHENYL-1-BROMOBUTANE
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Evidence is presented to show that product development from photolysis of 4-phenyl-1-iodobutane occurs essentially from an ionic species.This conclusion is in accord with our earlier suggestion that in the photocyclization of citronellyl iodide and related compounds, carbocations are involved.
- Subbarao, Kanury V.,Damodaran, N.P.,Dev, Sukh
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p. 2543 - 2548
(2007/10/02)
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- PHOTOLYSIS OF 2-PHENYLETHYL AND 4-PHENYL-1-BUTYL HALIDES IN ALCOHOLIC SOLVENTS
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Photolysis of 2-phenylethyl bromide in the lower alcohols gave the corresponding carbinols and ethers as the main products.With 2-phenylethyl iodide, the products were almost exclusively of the latter type, while 4-phenyl-1-butyl halides gave n-butylbenzene, 4-phenyl-1-butene and tetralin.It is shown that each of these products may be assigned to an ionic or radical pathway and that both the nature of the sovent and the structure of the substrate affect the course of photolysis.There is a substrate dependent preference for specific reactions along pathways of both the radical and ionic types.The variations in product composition and distribution are rationalized in terms of the relative efficiencies furnished in these pathways for the relaxation of high energy intermediates produced in the initial stages of photolysis.Intervention by the phenyl group is more pronunced in the case of 2-phenylethyl halides than in the case of the higher homologues and more effective in the ionic pathway.
- Bhalerao, V. K.,Nanjundiah, B. S.,Sonawane, H. R.,Nair, P. M.
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p. 1487 - 1496
(2007/10/02)
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- Conversion of Alcohols into Alkyl Bromides using Polymer-supported Triphenylphosphine Dibromide and Polymer-supported Triphenylphosphine and Carbon Tetrabromide
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Alcohols were converted into alkyl bromides by reaction with polymer-supported triphenylphosphine dibromide and with polymer-supported triphenylphosphine and carbon tetrabromide.With both reagents excellent yields of bromides were obtained, but reaction with the latter reagent were faster and cleaner and in favourable cases high yields of bromide were obtained within 15 min at 20 deg C.An advantage of the polymer-supported reagents is that product isolation is facilitated by the ready separation of the supported from the non-supported species.
- Hodge, Philip,Khoshdel, Ezzatollah
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p. 195 - 198
(2007/10/02)
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- A NOVEL ONE STEP CONVERSION OF ALCOHOLS INTO ALKYL BROMIDES OR IODIDES
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Alcohols are converted in high yields into alkyl bromides or iodides by a one step reaction with N,N'-carbonyldiimidazole and an excess of reactive halides such as allyl bromide or methyl iodide.KEYWORDS - alcohol; N,N'-carbonyldiimidazole; bromination; iodination; 1-alkoxycarbonylimidazole; 1-alkoxycarbonyl-3-substituted imidazolium salt; allyl bromide; methyl iodide
- Kamijo, Tetsuhide,Harada, Hiromu,Iizuka, Kinji
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p. 4189 - 4192
(2007/10/02)
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- Carbanion Rearrangements by Intramolecular 1,ω Proton Shifts, III. The Reaction of 2-, 3-, 4-, and 5-Phenylalkyllithium Compounds
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Upon addition of THF to a solution of 4-phenylbutyllithium (2) in diethyl ether a rapid intramolecular 1,4 proton shift takes place with the formation of 1-phenylbutyllithium (5).Similarly, although somewhat more slowly, 5-phenylpentyllithium (82) rearranges to 1-phenylpentyllithium (83) via 1,5 proton transfer.The corresponding rearrangements by 1,2 or 1,3 hydrogen shifts, however, starting with 2-phenylethyllithium (1) and 3-phenylpropyllithium (54), respectively, were not detected.With 3-phenylpropyllithium (54) a slow intramolecular 1,5 transfer an ortho proton is observed instead, yielding o-propylphenyllithium (100).The corresponding 1,6 shift with 4-phenylbutyllithium (2) was also detected in a minor amount in addition to the 1,4 proton shift already mentioned.There is no indication, however, for a 1,4 transfer of an ortho proton in 2-phenylethyllithium (1).The reaction products in this case can be exclusively explained by intermolecular transmetallation reactions.All ω-phenylalkyllithium compounds under investigation show interesting side and secondary reactions being rather different in deuterated solvents and in deuteriumfree solvents, respectively, due to the isotope effects.The analysis of the products is accomplished by 1H-NMR spectroscopy and, after derivatization, with the help of a GC-MS-combination.Stereoelectronic reasons are made responsible for the failure of the intramolecular 1,2 and 1,3 proton shift in these systems.
- Maercker, Adalbert,Passlack, Michael
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p. 540 - 577
(2007/10/02)
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- Synthesis and evaluation of novel alkylpiperazines as potential dopamine antagonists
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Several alkylpiperazines, monocyclic subfragments of known tricyclic neuroleptic agents, were evaluated as dopamine antagonists in the isolated rabbit ear artery preparation. Compounds prepared and evaluated are of the general structure Ar-X-(CH2)(n)-Y, where X = C, O, and N, n = 1-3, and Y, for the most part, was 4-methylpiperazine. Those compounds where X = NH, n = 3, and X = (Z)-CH=CH, n = 2, with an electron-witdrawing group meta to the side chain, possess dopamine antagonist activity comparable to that of clozapine. It is concluded that the entire tricyclic structure of phenothiazine-like agents (or at least more than a monocyclic ring system) is necessary for optimal activity as a dopamine antagonist in the receptor preparation used in this study.
- Glennon,Salley Jr.,Steinsland,Nelson
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p. 678 - 683
(2007/10/02)
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- Phenyl alkyleneoxy phenyl alkanoic acid esters
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Pharmaceutical compositions having hypolipidaemic and/or hypoglycaemic activity, contain a substituted (4-carboxyphenoxy) phenyl alkane derivative.
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- Anti-arthritic 1H-pyrimido-(5,4,3-kl)phenothiazine-1,3(2H)-diones and 1-thiones
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1H-Pyrimido[5,4,3-kl]phenothiazine-1,3(2H)-diones are prepared from the corresponding 1-thione-3-one compounds by methylation followed by acid hydrolysis. The 1,3-dione products and 1-thione-3-one intermediates are useful as anti-arthritic agents.
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- Phenyl-substituted prostaglandin-F type analogs
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This invention is a group of phenyl-substituted PGE-type, PGF-type, PGA-type and PGB-type compounds, and processes for making them. These compounds are useful for a variety of pharmacological purposes, including anti-ulcer, inhibition of platelet aggregation, increase of nasal patency, labor inducement at term, and wound healing.
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