- A new facile synthesis of a thromboxane B2 precursor
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A short, stereocontrolled synthesis of a key intermediate in the synthesis of thromboxane B2 is described. The approach is based on the use of N,N-diethyl(phenylsulfonyl)acetamide as nucleophile in a palladium-catalysed nucleophilic substitutio
- Booysen,Holzapfel
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Read Online
- Probing phenylcarbamoylazinane-1,2,4-triazole amides derivatives as lipoxygenase inhibitors along with cytotoxic, ADME and molecular docking studies
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Hunting small molecules as anti-inflammatory agents/drugs is an expanding and successful approach to treat several inflammatory diseases such as cancer, asthma, arthritis, and psoriasis. Besides other methods, inflammatory diseases can be treated by lipoxygenase inhibitors, which have a profound influence on the development and progression of inflammation. In the present study, a series of new N-alkyl/aralky/aryl derivatives (7a-o) of 2-(4-phenyl-5-(1-phenylcarbamoyl)piperidine-4H-1,2,4-triazol-3-ylthio)acetamide was synthesized and screened for their inhibitory potential against the enzyme 15-lipoxygenase. The simple precursor ethyl piperidine-4-carboxylate (a) was successively converted into phenylcarbamoyl derivative (1), hydrazide (2), semicarbazide (3) and N-phenylated 5-(1-phenylcarbamoyl)piperidine-1,2,4-triazole (4), then in combination with electrophiles (6a-o) through further multistep synthesis, final products (7a-o) were generated. All the synthesized compounds were characterized by FTIR, 1H, 13C NMR spectroscopy, EIMS, and HREIMS spectrometry. Almost all the synthesized compounds showed excellent inhibitory potential against the tested enzyme. Compounds 7c, 7f, 7d, and 7g displayed potent inhibitory potential (IC50 9.25 ± 0.26 to 21.82 ± 0.35 μM), followed by the compounds 7n, 7h, 7e, 7a, 7b, 7l, and 7o with IC50 values in the range of 24.56 ± 0.45 to 46.91 ± 0.57 μM. Compounds 7c, 7f, 7d exhibited 71.5 to 83.5% cellular viability by MTT assay compared with standard curcumin (76.9%) when assayed at 0.125 mM concentration. In silico ADME studies supported the drug-likeness of most of the molecules. In vitro inhibition studies were substantiated by molecular docking wherein the phenyl group attached to the triazole ring was making a π-δ interaction with Leu607. This work reveals the possibility of a synthetic approach of compounds in relation to lipoxygenase inhibition as potential lead compounds in drug discovery.
- Muzaffar, Saima,Shahid, Wardah,Riaz, Naheed,Saleem, Muhammad,Ashraf, Muhammad,Aziz-ur-Rehman,Bashir, Bushra,Kaleem, Ayesha,al-Rashida, Mariya,Baral, Bikash,Bhattarai, Keshab,Gross, Harald
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- Facile peripheral modification of N-confused porphyrin
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An improved methodology for the N-alkylation of the porphyrin isomer N-confused porphyrin is presented. The combination of polar solvent conditions and the use of the base Cs2CO3 affords externally modified products in high yield wit
- Qu, Wenchao,Ding, Tang,Cetin, Anil,Harvey, John D.,Taschner, Michael J.,Ziegler, Christopher J.
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Read Online
- Identification of phenylcarbamoylazinane-1,3,4-oxadiazole amides as lipoxygenase inhibitors with expression analysis and in silico studies
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In search for new anti-inflammatory agents that inhibit the enzymes of arachidonic acid pathway as the drug targets, the present article describes the screening of 1,3,4-oxadiazole analogues against lipoxygenase (LOX) enzyme. The work is based on the synthesis of new N-alkyl/aralky/aryl derivatives (6a-o) of 2-(4-phenyl-5-(1-phenylcarbamoylpiperidine)-4H-1,3,4-oxadiazol-3-ylthio)acetamide which were obtained by the reaction of 1,3,4-oxadiazole (3) with various electrophiles (5a-o), in KOH. The synthesized analogues showed potent to moderate inhibitory activity against the soybean 15-LOX enzyme; especially 6g, 6b, 6a and 6l displayed the potent inhibitory potential with IC50 values 7.15 ± 0.26, 9.32 ± 0.42, 15.83 ± 0.45 & 18.37 ± 0.53 μM, respectively, while excellent to moderate inhibitory profiles with IC50 values in the range of 26.13–98.21 μM were observed from the compounds 6k, 6m, 6j, 6o, 6h, 6f, 6n and 6c. Most of the active compounds exhibited considerable cell viability against blood mononuclear cells (MNCs) at 0.25 mM by MTT assay except 6f, 6h, 6k and 6m which showed around 50% cell viability. Flow cytometry studies of the selected compounds 6a, 6j and 6n revealed that these caused 79.5–88.51% early apoptotic changes in MNCs compared with 4.26% for control quercetin at their respective IC50 values. The relative expression of 5-LOX gene was monitored in MNCs after treatment with these three molecules and all down-regulated the enzyme activity. In silico ADME and molecular docking studies further supported these studies of oxadiazole derivatives and considered it as potential ‘lead’ compounds in drug discovery and development.
- Bashir, Bushra,Shahid, Wardah,Ashraf, Muhammad,Saleem, Muhammad,Aziz-ur-Rehman,Muzaffar, Saima,Imran, Muhammad,Amjad, Hira,Bhattarai, Keshab,Riaz, Naheed
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Read Online
- Quaternary ammonium salt type honokiol/magnolol derivative as well as preparation method and application thereof
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The invention discloses a series of novel quaternary ammonium salt honokiol/magnolol derivatives as well as a preparation method and application thereof. According to the series of compounds, honokiol/magnolol is taken as a raw material, a series of novel quaternary ammonium salt honokiol/magnolol derivatives are prepared on phenolic hydroxyl groups of honokiol/magnolol through a coupling reaction, and the structural general formula is shown in the specification. The compound disclosed by the invention has very strong antibacterial activity on staphylococcus aureus ATCC 29213 and clinically separated methicillin-resistant staphylococcus aureus (MRSA), most of the derivatives are higher than parent honokiol/magnolol, and the activity of part of the target derivatives is higher than that of a contrast drug levofloxacin. The compound is expected to be used for preparing drugs for resisting staphylococcus aureus and methicillin-resistant staphylococcus aureus.
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Paragraph 0039; 0050-0051
(2021/06/26)
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- Copper-catalyzed oxyvinylation of diazo compounds
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A copper(I)-catalyzed vinylation of diazo compounds with vinylbenziodoxolone reagents (VBX) as partners is reported. The transformation tolerates diverse functionalities on both reagents delivering polyfunctionalized vinylated products. The strategy was successfully extended to a three-component/intermolecular version with alcohols. The obtained products contain synthetically versatile functional groups, such as an aryl iodide, an ester, and an allylic leaving group, enabling further modification.
- Pisella, Guillaume,Gagnebin, Alec,Waser, Jerome
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supporting information
p. 3884 - 3889
(2020/05/14)
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- Design, Synthesis, Antimicrobial Evaluation, and Laccase Catalysis Effect of Novel Benzofuran–Oxadiazole and Benzofuran–Triazole Hybrids
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Novel structural hybrids of benzofuran–oxadiazole and benzofuran–triazole have been synthesized and evaluated for their potential against Staphylococcus aureus, Bacillus subtilis, and Escherichia coli. The excellent antibiotic activity was shown by compou
- Faiz, Sadia,Zahoor, Ameer Fawad,Ajmal, Muhammad,Kamal, Shagufta,Ahmad, Sajjad,Abdelgawad, Abdelrahman M.,Elnaggar, Mehrez E.
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p. 2839 - 2852
(2019/11/03)
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- Novel potential pyrazolopyrimidine based translocator protein ligands for the evaluation of neuroinflammation with PET
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Translocator protein (TSPO) is an interesting biological target because TSPO overexpression is associated with microglial activation caused by neuronal damage or neuroinflammation, and these activated microglia are involved in several central nervous syst
- Kwon, Young-Do,Kang, Shinwoo,Park, Hyunjun,Cheong, Il-koo,Chang, Keun-A,Lee, Sang-Yoon,Jung, Jae Ho,Lee, Byung Chul,Lim, Seok Tae,Kim, Hee-Kwon
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p. 292 - 306
(2018/10/15)
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- Organosilicon Reducing Reagents for Stereoselective Formations of Silyl Enol Ethers from α-Halo Carbonyl Compounds
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Salt-free stereoselective synthesis of silyl enol ethers was achieved by treating α-halo carbonyl compounds with 2,3,5,6-tetramethyl-1,4-bis(trimethylsilyl)-1,4-dihydropyrazine. In this reaction, easily removable trimethylsilyl halides and 2,3,5,6-tetramethylpyrazine were generated as the reaction byproducts. Due to the inertness of the reaction byproducts, we found a one-pot transformation of the in situ generated silyl enol ethers into various α-functionalized carbonyls by reaction with Togni-II reagent or aldehydes.
- Pramanik, Suman,Rej, Supriya,Kando, Shun,Tsurugi, Hayato,Mashima, Kazushi
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p. 2409 - 2417
(2018/02/23)
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- Enantioselective Spirocyclopropanation of para-Quinone Methides Using Ammonium Ylides
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The use of Cinchona alkaloid-based chiral ammonium ylides allows for the first highly enantioselective and broadly applicable spirocyclopropanation reactions of para-quinone methides. This strategy provides a straightforward protocol toward the chiral spiro[2.5]octa-4,7-dien-6-one skeleton, which is a frequently found structural motif in important biologically active molecules.
- Roiser, Lukas,Waser, Mario
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supporting information
p. 2338 - 2341
(2017/05/12)
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- Radiosynthesis of SPECT tracers: Via a copper mediated 123I iodination of (hetero)aryl boron reagents
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A general method for the copper mediated nucleophilic 123I-iodination of (hetero)aryl boronic esters and acids has been developed. The broad substrate scope of this radiosynthetic approach allows access to [123I]DPA-713, [123I]IMPY, [123I]MIBG and [123I]IPEB that are four commonly used SPECT radiotracers. Our results infer that aryl boronic reagents can now be employed as common precursors for both fluorine-18 and iodine-123 radiolabelling.
- Wilson, Thomas C.,McSweeney, Greg,Preshlock, Sean,Verhoog, Stefan,Tredwell, Matthew,Cailly, Thomas,Gouverneur, Véronique
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supporting information
p. 13277 - 13280
(2016/11/17)
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- Design, synthesis and evaluation of novel 19F magnetic resonance sensitive protein tyrosine phosphatase inhibitors
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Fluorine is a highly attractive element for both medicinal chemistry and imaging technologies. To facilitate protein tyrosine phosphatase (PTP)-targeted drug discovery and imaging-guided PTP research on fluorine, several highly potent and 19F MR sensitive PTP inhibitors were discovered through a structure-based focused library strategy.
- Li, Yu,Xia, Guiquan,Guo, Qi,Wu, Li,Chen, Shizhen,Yang, Zhigang,Wang, Wei,Zhang, Zhong-Yin,Zhou, Xin,Jiang, Zhong-Xing
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supporting information
p. 1672 - 1680
(2016/08/24)
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- Copper-Catalyzed Oxy-Alkynylation of Diazo Compounds with Hypervalent Iodine Reagents
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Alkynes have found widespread applications in synthetic chemistry, biology, and materials sciences. In recent years, methods based on electrophilic alkynylation with hypervalent iodine reagents have made acetylene synthesis more flexible and efficient, but they lead to the formation of one equivalent of an iodoarene as side-product. Herein, a more efficient strategy involving a copper-catalyzed oxy-alkynylation of diazo compounds with ethynylbenziodoxol(on)e (EBX) reagents is described, which proceeds with generation of nitrogen gas as the only waste. This reaction is remarkable for its broad scope in both EBX reagents and diazo compounds. In addition, vinyl diazo compounds gave enynes selectively as single geometric isomers. The functional groups introduced during the transformation served as easy handles to access useful building blocks for synthetic and medicinal chemistry.
- Hari, Durga Prasad,Waser, Jerome
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supporting information
p. 2190 - 2193
(2016/03/08)
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- ALKYNE COMPOUNDS AS S-NITROSOGLUTATHIONE REDUCTASE INHIBITORS
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Provided are compounds of formula (Ia) and pharmaceutically acceptable salts thereof, wherein A, B, R 1, R 2, m and n are as defined herein, which are active as inhibitors of S-Nitrosoglutathione reductase (GSNOR). These compounds prevent, inhibit, or suppress the action of GSNOR and are therefore useful in the treatment of GSNOR mediated diseases, disorders, syndromes or conditions such as, e.g., pulmonary hypertension, acute respiratory distress syndrome (ARDS), asthma, bronchospasm, cough, pneumonia, pulmonary fibrosis, interstitial lung diseases, cystic fibrosis and chronic obstructive pulmonary disease (COPD).
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Page/Page column 119
(2016/05/02)
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- ORALLY ADMINISTRABLE VIRIDIOFUNGIN DERIVATIVE HAVING ANTI-HCV ACTIVITY
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An object of the present invention is to provide a compound that is useful as an orally available anti-HCV agent. The present invention relates to a compound represented by formula (1) or a pharmaceutically acceptable salt thereof. This compound has an anti-HCV activity and is useful as a medicine.
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Paragraph 0479; 0480
(2015/07/02)
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- NOVEL CELL-PERMEABLE SUCCINATE COMPOUNDS
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The present invention provides novel cell-permeable succinates and cell permeable precursors of succinate aimed at increasing ATP-production in mitochondria. The main part of ATP produced and utilized in the eukaryotic cell originates from mitochondrial oxidative phosphorylation, a process to which high-energy electrons are provided by the Kreb's cycle. Not all Kreb's cycle intermediates are readily permeable to the cellular membrane, one of them being succinate. The provision of the novel cell permeable succinates is envisaged to allow passage over the cellular membrane and thus the cell permeable succinates can be used to enhance mitochondrial ATP-output.
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Page/Page column 71
(2015/11/03)
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- Structure-activity relationships of oxysterol-derived pharmacological chaperones for Niemann-Pick type C1 protein
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Niemann-Pick disease type C is a fatal neurodegenerative disease, and its major cause is mutations in NPC1 gene. This gene encodes NPC1 protein, a late endosomal polytopic membrane protein required for intracellular cholesterol trafficking. One prevalent mutation (I1061T) has been shown to cause a folding defect, which results in failure of endosomal localization of the protein, leading to loss-of-function phenotype. We have previously demonstrated that several oxysterols and their derivatives act as pharmacological chaperones; binding of these compounds to NPC1I1061T mutant protein corrects the localization/maturation defect of the mutant protein. Here, we disclose detailed structure-activity relationships of oxysterol derivatives as pharmacological chaperones for NPC1I1061T mutant.
- Ohgane, Kenji,Karaki, Fumika,Noguchi-Yachide, Tomomi,Dodo, Kosuke,Hashimoto, Yuichi
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supporting information
p. 3480 - 3485
(2014/07/22)
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- Synthesis of berberine bromide analogs containing tertiary amides of acetic acid in the 9-O-position
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9-O-Acetamide analogs of berberine bromide were prepared in 20-87% yields via reaction of the isoquinoline alkaloid berberrubine with tertiary amides of bromoacetic acid. Aminolysis did not occur during reaction of methyl-2-(9-demethoxyberberine bromide-9-yl)hydroxyacetate with secondary amines. The corresponding acid or its ethyl ester was isolated.
- Nechepurenko,Komarova,Vasil'ev,Salakhutdinov
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p. 1047 - 1053
(2013/04/23)
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- Copper(II)-acid co-catalyzed intermolecular substitution of electron-rich aromatics with diazoesters
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The intermolecular aromatic substitution of N,N-dialkylanilines and alkoxybenzenes with diazoesters is shown to proceed in the presence of catalytic amounts of both copper(II) salt and acid (Lewis or Br?nsted). This method is a mild and rare metal-free C-C bond formation reaction between aromatic (sp2) and aliphatic (sp3) carbons.
- Tayama, Eiji,Ishikawa, Moe,Iwamoto, Hajime,Hasegawa, Eietsu
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supporting information; experimental part
p. 5159 - 5161
(2012/10/07)
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- A formal method for the de-N,N-dialkylation of Sommelet-Hauser rearrangement products
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Selective amine de-alkylation enables the conversion of Sommelet-Hauser rearrangement products into 2-aryl-2-bromoacetic acid derivatives. These compounds are valuable synthetic intermediates in the synthesis of α-aryl-α-amino or α-aryl-β-amino acid deriv
- Tayama, Eiji,Sato, Ryota,Takedachi, Keisuke,Iwamoto, Hajime,Hasegawa, Eietsu
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supporting information; experimental part
p. 4710 - 4718
(2012/07/28)
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- Ru(II)-Pheox catalyzed N-H insertion reaction of diazoacetamides: Synthesis of N-substituted α-aminoamides
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An efficient protocol for the preparation of α-aminoamides was developed via the Ru(II)-dm-Pheox catalyzed N-H insertion reaction of various diazoacetamides with several amines, including aniline. This catalytic N-H insertion reaction was also applied to the synthesis of 2-(2-methylquinolin-4- ylamino)-N-phenylacetamide, a potential antileishmanial agent.
- Chanthamath, Soda,Thongjareun, Songkharm,Shibatomi, Kazutaka,Iwasa, Seiji
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supporting information; experimental part
p. 4862 - 4865
(2012/09/08)
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- Stereoselective synthesis of ambiphilic alkenes via regioselective methylation of α-trifluoromethanesulfonyl carbonyl compounds with trimethylsilyldiazomethane
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α-Trifluoromethanesulfonyl esters, ketones and amides are C-H acids capable of reacting with trimethylsilyldiazomethane to afford the corresponding ambiphilic alkenes. While esters were found to be non-selective, ketones were highly regioselective for O-methylation and displayed variable E/Z stereoselectivity. Amides were observed to be both highly regio- and stereoselective, affording O-methylation with exclusive formation of the Z-alkene.
- Kong, Han Il,Crichton, Jennifer E.,Manthorpe, Jeffrey M.
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supporting information; experimental part
p. 3714 - 3717
(2011/08/06)
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- Synthesis and structure-activity relationship studies in translocator protein ligands based on a pyrazolo[3,4-b]quinoline scaffold
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As a further development of our large program focused on the medicinal chemistry of translocator protein [TSPO (18 kDa)] ligands, a new class of compounds related to alpidem has been designed using SSR180575, emapunil, and previously published pyrrolo[3,4-b]quinoline derivatives 9 as templates. The designed compounds were synthesized by alkylation of the easily accessible 4-methyl-2-phenyl-1H-pyrazolo[3,4-b]quinolin-3(2H)-one derivatives 13-15 with the required bromoacetamides. Along with the expected 2-(4-methyl-3-oxo-2- phenyl-2,3-dihydro-1H-pyrazolo[3,4-b]quinolin-1-yl)acetamide derivatives 10, 2-(4-methyl-3-oxo-2-phenyl-2H-pyrazolo[3,4-b]quinolin-9(3H)-yl)acetamide isomers 11 were isolated and characterized. The high TSPO affinity shown by new pyrazolo[3,4-b]quinoline derivatives 10 and especially 11 leads the way to further expand the chemical diversity in TSPO ligands and provides new templates and structure-affinity relationship data potentially useful in the design of new anxiolytic and neuroprotective agents.
- Cappelli, Andrea,Bini, Giulia,Valenti, Salvatore,Giuliani, Germano,Paolino, Marco,Anzini, Maurizio,Vomero, Salvatore,Giorgi, Gianluca,Giordani, Antonio,Stasi, Luigi Piero,Makovec, Francesco,Ghelardini, Carla,Di Cesare Mannelli, Lorenzo,Concas, Alessandra,Porcu, Patrizia,Biggio, Giovanni
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supporting information; experimental part
p. 7165 - 7175
(2011/12/04)
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- On the mechanism of ylide-mediated cyclopropanations: Evidence for a proton-transfer step and its effect on stereoselectivity
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In this paper, we describe studies on the cyclopropanation of Michael acceptors with chiral sulfur ylides. It had previously been found that semi-stabilized sulfonium ylides (e.g., Ph-stabilized) reacted with cyclic and acyclic enones and substituted acrylates with high ee and that stabilized sulfonium ylides (e.g., ester-stabilized) reacted with cyclic enones again with high ee. The current study has focused on the reactions of stabilized sulfonium ylides with acyclic enones which unexpectedly gave low ee. Furthermore, a clear correlation of ee with ylide stability was observed in reactions with methyl vinyl ketone (MVK): ketone-stabilized ylide gave 25% ee, ester-stabilized ylide gave 46% ee, and amide-stabilized ylide gave 89% ee. It is believed that following betaine formation an unusual proton transfer step intervenes which compromises the enantioselectivity of the process. Thus, following addition of a stabilized ylide to the Michael acceptor, rapid and reversible intramolecular proton transfer within the betaine intermediate, prior to ring closure, results in an erosion of ee. Proton transfer occurred to the greatest extent with the most stabilized ylide (ketone). When the same reactions were carried out with deuterium-labeled sulfonium ylides, higher ees were observed in all cases since proton/deuteron transfer was slowed down. The competing proton transfer or direct ring-closure pathways that are open to the betaine intermediate apply not only to all sulfur ylides but potentially to all ylides. By applying this model to S-, N-, and P-ylides we have been able to rationalize the outcome of different ylide reactions bearing a variety of substituents in terms of chemo- and enantioselectivity.
- Riches, Samantha L.,Saha, Chandreyee,Filgueira, Noelia Fontan,Grange, Emma,McGarrigle, Eoghan M.,Aggarwal, Varinder K.
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supporting information; experimental part
p. 7626 - 7630
(2010/07/09)
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- Remarkable enhancement effect of potassium tert-butoxide/THF solution in base-induced Sommelet-Hauser rearrangements
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A solution of potassium tert-butoxide in THF was shown to remarkably enhance the base-induced Sommelet-Hauser rearrangement of N-benzylic amino acid-derived ammonium ylides.
- Tayama, Eiji,Takedachi, Keisuke,Iwamoto, Hajime,Hasegawa, Eietsu
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supporting information; experimental part
p. 9389 - 9395
(2011/01/12)
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- Copper(II) triflate catalyzed intermolecular aromatic substitution of N,N-disubstituted anilines with diazo esters
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The intermolecular aromatic substitution of N,N-disubstituted anilines with diazo esters is achieved under mild conditions in the presence of a catalytic amount of copper(II) triflate (up to 89 % yield). The scope and limitations regarding substrates, diazo esters, and ligands in this reaction are described. The intermolecular aromatic substitution of N,N-disubstituted anilines with diazo esters is shown to proceed under mild conditions in the presence of a catalytic amount of copper(II) triflate/ligand complex(up to 89 % yield). The scope and limitations regarding substrates, diazoesters, and ligands in this reaction are described. Copyright
- Tayama, Eiji,Yanaki, Tomoyo,Iwamoto, Hajime,Hasegawa, Eietsu
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supporting information; experimental part
p. 6719 - 6721
(2011/02/28)
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- Information transfer in calix[4]arenes: influence of upper rim substitution on alkaline metal complexation at the lower rim
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Novel calix[4]arene amides have been synthesized and their interaction with alkaline cations has been evaluated through extracting aqueous solutions of Li-, Na- and K-picrates with solutions of calix[4]arene amides in CH2Cl2. Electro
- Schühle, Daniel T.,Klimosch, Sascha,Schatz, Jürgen
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p. 5800 - 5803
(2008/12/22)
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- A CALIXARENE BISPHOSPHITE LIGAND FOR USE IN HYDROFORMYLATION PROCESSES
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A calixarene bisphosphite composition for use as a ligand in a transition metal-ligand complex catalyst and in a complex catalyst precursor. The ligand is especially useful in catalysts and catalyst precursors for hydroformylation processes wherein a raffinate stream comprising a mixture of alpha, beta, and iso-olefinic isomers is hydroformylated in the presence of carbon monoxide, hydrogen, and the transition metal-ligand complex catalyst to form a mixture of linear and branched aldehyde products. The complex catalyst selectively converts the alpha and beta olefin reactants more rapidly than the iso-olefin reactant resulting in an improved molar ratio of normal (linear) to branched aldehyde products. The unconverted iso-olefinic isomer is thereafter readily separated from the aldehyde product mixture.
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Page/Page column 21-22
(2008/12/04)
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- Palladium-catalyzed intermolecular α-arylation of zinc amide enolates under mild conditions
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The intermolecular α-arylation and vinylation of amides by palladium-catalyzed coupling of aryl bromides and vinyl bromides with zinc enolates of amides is reported. Reactions of three different types of zinc enolates have been developed. The reactions of
- Hama, Takuo,Culkin, Darcy A.,Hartwig, John F.
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p. 4976 - 4985
(2007/10/03)
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- THERAPEUTICS
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The present invention relates to the use of a compound of formula (I); wherein: R1 comprises a carbonyl group and R2 is a hydrocarbyl group; optionally wherein said ring is further substituted; or a pharmaceutically acceptable salt thereof; in the manufacture of a medicament for use in one or more of: modulating the release of intracellular calcium from a store controlled by nicotinic acid adenine dinucleotide phosphate; modulating calcium spikes in mammalian cells; treating diseases in one or more of brain, heart, pancreatic cells (e.g. pancreatic acinar and pancreatic beta cells), immune cells, T-cells, haemopoietic cells including phagocytes; treating diseases in one or more of brain, heart, pancreatic cells (e.g. pancreatic acinar and pancreatic beta cells), immune cells, T-cells, haemopoietic cells including phagocytes by modulating the release of intracellular calcium from a store controlled by nicotinic acid adenine dinucleotide phosphate; treating diseases in one or more of brain, heart, and T-cells by modulating calcium spikes in mammalian cells.
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Page/Page column 54-55
(2008/06/13)
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- SULFONYLAMINO-ACETIC ACID DERIVATIVES
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The invention relates to novel sulfonylamino-acetic acid derivatives and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of such compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as orexin receptor antagonists.
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- Palladium-catalyzed α-arylation of esters and amides under more neutral conditions
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Two procedures for the ∞-arylation of carbonyl compounds under conditions that are more neutral than those of reactions of aryl halides with alkali metal enolates are reported. The first procedure rests upon the development of catalysts bearing the hindered pentaphenylferrocenyl di-tert-butylphosphine (Q-phos) and the highly reactive dimeric Pd(I) complex {P(t-Bu)3]PdBr}2. By this procedure, zinc enolates prepared from ∞-bromo esters and amides react with aryl halides to form ∞-aryl esters and amides in high yields under mild conditions with 1-2 mol % catalyst and with remarkable functional group tolerance. By the second procedure, silyl ketene and silyl ketimine acetals react with aryl bromides in the presence of substoichiometric zinc fluoride, 1 mol % Pd(dba)2, and 2 mol % P(t-Bu)3 in DMF solvent at 80 °C. Reactions of zinc tert-butyl acetate and propionate enolates and trimethylsilyl ketene acetals of tert-butyl propionate and methyl isobutyrate with aryl bromides bearing electron-donating and potentially reactive, base-sensitive electron-withdrawing groups and with pyridyl bromides are reported. In addition, the diastereoselective coupling of phenyl bromide with an imide enolate bearing the Evans auxiliary is reported, and this study shows that racemization of base-sensitive stereocenters does not occur during the coupling process under these more neutral conditions. Copyright
- Hama, Takuo,Liu, Xiaoxiang,Culkin, Darcy A.,Hartwig, John F.
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p. 11176 - 11177
(2007/10/03)
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- Fibrinogen receptor antagonists
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Fibrinogen receptor antagonists having the structure, for example, of STR1 for example STR2
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- Discovery of 1,5-benzodiazepines with peripheral cholecystokinin (CCK-A) receptor agonist activity. 1. Optimization of the agonist "trigger"
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Directed screening of compounds selected from the Glaxo registry file for contractile activity on the isolated guinea pig gallbladder (GPGB) identified a series of 1,5-benzodiazepines with peripheral cholecystokinin (CCK) receptor agonist activity. Agonis
- Aquino, Christopher J.,Armour, Duncan R.,Berman, Judd M.,Birkemo, Larry S.,Carr, Robin A. E.,Croom, Dallas K.,Dezube, Milana,Dougherty Jr., Robert W.,Ervin, Gregory N.,Grizzle, Mary K.,Head, Julie E.,Hirst, Gavin C.,James, Michael K.,Johnson, Michael F.,Miller, Laurence J.,Queen, Kennedy L.,Rimele, Thomas J.,Smith, David N.,Sugg, Elizabeth E.
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p. 562 - 569
(2007/10/03)
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- Cavity-shaped phosphane ligands. Phosphane-amide hybrids based on a calixarene matrix and their chelating behavior towards platinum and rhodium
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The di(amide)-diphosphane hybrids 5,11,17,23-tetra-tert-butyl-25,27-bis(diethylcarbamoylmethoxy)-26,28-bis(diphenylphosphinomethoxy)calixarene (cone) 7 and (R,R)-(+)-5,11,17,23-tetra-tert-butyl-25,27-bis-26,28-bis(diphe
- Loeber, Cyrille,Wieser, Catherine,Matt, Dominique,Cian, Andre De,Fischer, Jean,Toupet, Loiec
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p. 166 - 177
(2007/10/02)
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