- [NO]- and [NN]-coordination mode rhodium complexes based on a flexible ligand: Synthesis, reactivity and catalytic activity
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A flexible [NON]-type ligand was prepared via a stepwise method. Air- and moisture-stable LL- (N,O-coordination mode) (1) and LX-type (N,N-coordination mode) (2) rhodium(i) complexes were synthesized based on this flexible ligand under different reaction conditions. The two rhodium complexes were isolated in good yields and characterized by elemental analysis and IR and NMR spectrometry. The molecular structures of complexes 1 and 2 were confirmed by single-crystal X-ray analysis. The cationic rhodium complex was shown to be a good catalyst for the hydrogenation of acetophenone derivatives without pre-dried solvents and reagents. Good efficiency was achieved for a series of substrates with either electron-donating or electron-withdrawing groups.
- Yao, Zi-Jian,Li, Kuan,Zhang, Jian-Yong,Deng, Wei
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Read Online
- Total Synthesis of (±)-2-Debromohymenin via Gold-Catalyzed Intramolecular Alkyne Hydroarylation
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An intramolecular, gold-catalyzed alkyne hydroarylation results in the formation of the core pyrroloazepinone framework of the hymenin group of oroidin alkaloids. Elaboration of the cyclic adduct via C2-azidation, bromination of the pyrrole, and deprotection set the stage for global reduction with Mo(CO)6 resulting in the formation 2-debromohymenin.
- Bhandari, Manojkumar R.,Doundoulakis, Thomas,Gout, Delphine,Lovely, Carl J.,Singh, Ravi P.,Torres, Fatima M.
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Read Online
- Daminin, a bioactive pyrrole alkaloid from the Mediterranean sponge Axinella damicornis
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The isolation and characterization of the known pyrrole alkaloid agelongine (6) and of the new natural product daminin (7), the bromine-free analogue of 6, from a specimen of the marine sponge Axinella damicornis is described. Compound 7 showed significant neuroprotective properties. Moreover, for the supply of sufficient material for future medicinal investigations, a short total synthesis of 7 was developed.
- Aiello, Anna,D'Esposito, Monica,Fattorusso, Ernesto,Menna, Marialuisa,Müller, Werner E.G.,Perovi?-Ottstadt, Sanja,Tsuruta, Hideyuki,Gulder, Tobias A.M.,Bringmann, Gerhard
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Read Online
- Compound, preparation method and applications thereof
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The invention provides an N-(4-cyclopropylnaphthyl)-formamide compound represented by a structural formula I, and a preparation method thereof, wherein R is defined in the specification. The inventionalso provides a preparation method of 4-cyclopropyl-1-naphthylamine, wherein the preparation method comprises: hydrolyzing the compound represented by the structural formula I in the presence of an alkali or an acid to obtain the 4-cyclopropyl-1-naphthylamine. The invention also provides a lesinurad preparation method, which comprises the following steps: preparing 4-cyclopropyl-1-naphthylamine from the compound represented by the structural formula I, and preparing Lesinurad according to the known synthetic route in the field.
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Paragraph 0069-0071
(2020/03/25)
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- Alternating current electrolysis for organic electrosynthesis: Trifluoromethylation of (hetero)arenes
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Paired electrolysis has a limited reaction scope for organic synthesis because it is often not compatible with reactions involving short-lived intermediates. We addressed this limitation using alternating current electrolysis (ACE). Using trifluoromethyla
- Rodrigo, Sachini,Um, Chanchamnan,Mixdorf, Jason C.,Gunasekera, Disni,Nguyen, Hien M.,Luo, Long
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supporting information
p. 6719 - 6723
(2020/07/30)
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- Triarylmethane Fluorophores Resistant to Oxidative Photobluing
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Spectral stability of small-molecule fluorescent probes is required for correct interpretation and reproducibility of multicolor fluorescence imaging data, in particular under high (de)excitation light intensities of super-resolution imaging or in single-molecule applications. We propose a synthetic approach to a series of spectrally stable rhodamine fluorophores based on sequential Ru- and Cu-catalyzed transformations, evaluate their stability against photobleaching and photoconversion in the context of other fluorophores using chemometric analysis, and demonstrate chemical reactivity of fluorophore photoproducts. The substitution patterns providing the photoconversion-resistant triarylmethane fluorophores have been identified, and the applicability of nonbluing labels in live-cell STED nanoscopy is demonstrated.
- Butkevich, Alexey N.,Bossi, Mariano L.,Lukinavi?ius, Gra?vydas,Hell, Stefan W.
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supporting information
p. 981 - 989
(2019/01/23)
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- N,N-coordination Rh complex as well as synthesis method and application thereof
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The invention belongs to the technical field of synthesis of organic metal compounds and particularly relates to an N,N-coordination Rh complex as well as a synthesis method and an application thereof. Firstly, a ligand is synthesized from methyl 1H-pyrrole-2-carboxylate as an initial raw material and further reacts with Rh(COD)2Cl, and a metal complex with Rh as a central atom is obtained. The synthesis method is simple, the complex as a catalyst can be used for catalyzing a series of reductive amination reactions of derivatives of acetophenone and aniline, and the product yield is good and is 90% or above.
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- Novel inhibitors of Staphylococcus aureus RnpA that synergize with mupirocin
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We recently discovered RnpA as a promising new drug discovery target for methicillin-resistant S. aureus (MRSA). RnpA is an essential protein that is thought to perform two required cellular processes. As part of the RNA degrasome Rnpa mediates RNA degradation. In combination with rnpB it forms RNase P haloenzymes which are required for tRNA maturation. A high throughput screen identified RNPA2000 as an inhibitor of both RnpA-associated activities that displayed antibacterial activity against clinically relevant strains of S. aureus, including MRSA. Structure-activity studies aimed at improving potency and replacing the potentially metabotoxic furan moiety led to the identification of a number of more potent analogs. Many of these new analogs possessed overt cellular toxicity that precluded their use as antibiotics but two derivatives, including compound 5o, displayed an impressive synergy with mupirocin, an antibiotic used for decolonizing MSRA whose effectiveness has recently been jeopardized by bacterial resistance. Based on our results, compounds like 5o may ultimately find use in resensitizing mupirocin-resistant bacteria to mupirocin.
- Lounsbury, Nicole,Eidem, Tess,Colquhoun, Jennifer,Mateo, George,Abou-Gharbia, Magid,Dunman, Paul M.,Childers, Wayne E.
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supporting information
p. 1127 - 1131
(2018/02/21)
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- INHIBITORS OF MUTANT ISOCITRATE DEHYDROGENASES AND COMPOSITIONS AND METHODS THEREOF
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The invention provides novel chemical compounds useful for treating cancer, or a related disease or disorder thereof, and pharmaceutical composition and methods of preparation and use thereof.
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Paragraph 00133
(2018/04/27)
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- Hemozoin inhibiting 2-phenylbenzimidazoles active against malaria parasites
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The 2-phenylbenzimidazole scaffold has recently been discovered to inhibit β-hematin (synthetic hemozoin) formation by high throughput screening. Here, a library of 325,728 N-4-(1H-benzo[d]imidazol-2-yl)aryl)benzamides was enumerated, and Bayesian statistics used to predict β-hematin and Plasmodium falciparum growth inhibition. Filtering predicted inactives and compounds with negligible aqueous solubility reduced the library to 35,124. Further narrowing to compounds with terminal aryl ring substituents only, reduced the library to 18, 83% of which were found to inhibit β-hematin formation 100 μM and 50% parasite growth 2 μM. Four compounds showed nanomolar parasite growth inhibition activities, no cross-resistance in a chloroquine resistant strain and low cytotoxicity. QSAR analysis showed a strong association of parasite growth inhibition with inhibition of β-hematin formation and the most active compound inhibited hemozoin formation in P. falciparum, with consequent increasing exchangeable heme. Pioneering use of molecular docking for this system demonstrated predictive ability and could rationalize observed structure activity trends.
- L'abbate, Fabrizio P.,Müller, Ronel,Openshaw, Roxanne,Combrinck, Jill M.,de Villiers, Katherine A.,Hunter, Roger,Egan, Timothy J.
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p. 243 - 254
(2018/10/15)
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- Palladium-Nanoparticles-Catalyzed Oxidative Annulation of Benzamides with Alkynes for the Synthesis of Isoquinolones
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A novel method to synthesize isoquinolones via oxidative annulation of N-alkoxy benzamides and alkynes using binaphthyl-stabilized palladium nanoparticles (Pd-BNP) as catalyst has been developed. This methodology affords various isoquinolone derivatives in good to excellent yields with high regioselectivities in the presence of air as oxidant. N-Methoxybenzothioamide was also found to undergo oxidative annulation with alkyne successfully and provided a sulfur analogue of isoquinolones in moderate yields. The Pd-BNP catalyst was easily recovered and reused up to four times without any apparent agglomeration. (Figure presented.).
- Sharma, Nidhi,Saha, Rajib,Parveen, Naziya,Sekar, Govindasamy
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supporting information
p. 1947 - 1958
(2017/06/09)
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- Design, synthesis and activity evaluation study of novel substituted N-sulfonyl homoserine lactone derivatives as bacterial quorum sensing inhibitors
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A novel series of N-sulfonyl homoserine lactone derivatives 7a–7m has been designed, synthesized, and evaluated for quorum sensing inhibitory activities through the violacein inhibition in Chromobacterium violaceum CV026. Compound 7e displayed the high level of inhibitory activity among all the compounds synthesized. Studies of structure-activity relationship indicated that compounds with thiophene group in side chain showed better activity than those substituted by furan, pyrrole, pyridyl, and phenethyl group. Thiophene substituted compounds which connected electron withdrawing group exhibited better inhibitory activity relate to those connected electron donating group. Further analysis indicated that compound bearing an electron withdrawing substituent at the position 2 of their thiophene ring exhibited superior activity against violacein production to those bearing the substituent at the position 3 and 4. Compound 7e in particular, with IC50 value of 6.19 μM, were identified as promising lead compounds for further development.
- Sun, Qi,Zhao, Mingming,Liang, Jingwei,Xiao, Junhai,Meng, Fanhao
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p. 3345 - 3353
(2017/11/16)
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- A mild method for the replacement of a hydroxyl group by halogen. 1. Scope and chemoselectivity
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α-Chloro-, bromo- and iodoenamines, which are readily prepared from the corresponding isobutyramides have been found to be excellent reagents for the transformation of a wide variety of alcohols or carboxylic acids into the corresponding halides. Yields are high and conditions are very mild thus allowing for the presence of sensitive functional groups. The reagents can be easily tuned allowing therefore the selective monohalogenation of polyhydroxylated molecules. The scope and chemoselectivity of the reactions have been studied and reaction mechanisms have been proposed.
- Munyemana, Fran?ois,George, Isabelle,Devos, Alain,Colens, Alain,Badarau, Eduard,Frisque-Hesbain, Anne-Marie,Loudet, Aurore,Differding, Edmond,Damien, Jean-Marie,Rémion, Jeanine,Van Uytbergen, Jacqueline,Ghosez, Léon
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p. 420 - 430
(2015/12/31)
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- SUBSTITUTED CYCLIC ETHER POLYMERS, AND CONJUGATES AND USES THEREOF
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Disclosed herein are substituted cyclic ether monomers, polymers, and drug conjugates thereof, which are useful for the treatment of diseases and conditions of the oral cavity. In particular, disclosed herein are monomers of Formula (I), polymers of Formu
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Paragraph 00100
(2016/09/22)
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- Optimisation of LRRK2 inhibitors and assessment of functional efficacy in cell-based models of neuroinflammation
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LRRK2IN1 is a highly potent inhibitor of leucine-rich repeat kinase 2 (LRRK2, IC50 = 7.9 nM), an established target for treatment of Parkinson's disease. Two LRRK2IN1 analogues 1 and 2 were synthesised which retained LRRK2 inhibitory activity (1: IC50 = 72 nM; 2: IC50 = 51 nM), were predicted to have improved bioavailability and were efficacious in cell-based models of neuroinflammation. Analogue 1 inhibited IL-6 secretion from LPS-stimulated primary human microglia with EC50 = 4.26 μM. In order to further optimize the molecular properties of LRRK2IN1, a library of truncated analogues was designed based on docking studies. Despite lacking LRRK2 inhibitory activity, these compounds show antineuroinflammatory efficacy at micromolar concentration. The compounds developed were valuable tools in establishing a cell-based assay for assessing anti-neuroinflammatory efficacy of LRRK2 inhibitors. Herein, we present data that IL-1β stimulated U87 glioma cell line is a reliable model for neuroinflammation, as data obtained in this model were consistent with results obtained using primary human microglia and astrocytes.
- Munoz, Lenka,Kavanagh, Madeline E.,Phoa, Athena F.,Heng, Benjamin,Dzamko, Nicolas,Chen, Ew-Jun,Doddareddy, Munikumar Reddy,Guillemin, Gilles J.,Kassiou, Michael
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supporting information
p. 29 - 34
(2015/03/30)
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- PYRROLOTRIAZINONE DERIVATIVES AS PI3K INHIBITORS
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New pyrrolotriazinone derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Phosphoinositide 3-Kinases (PI3Ks).
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Page/Page column 66-67
(2014/05/07)
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- COMPOUNDS USEFUL FOR THE TREATMENT OF METABOLIC DISORDERS AND SYNTHESIS OF THE SAME
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The present invention provides compounds of Formula (I): wherein variables X, Y, Z and R1 are as described herein. Some of the compounds described herein are glutamate dehydrogenase activators. The invention is also directed to pharmaceutical compositions comprising these compounds, uses of these compounds and compositions in the treatment of metabolic disorders as well as synthesis of the compounds.
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Page/Page column 71
(2014/10/18)
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- Catalytic hydroamination of unactivated olefins using a Co catalyst for complex molecule synthesis
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Functional group tolerance is one of the important requirements for chemical reactions, especially for the synthesis of complex molecules. Herein, we report a mild, general, and functional group tolerant intramolecular hydroamination of unactivated olefins using a Co(salen) complex, an N-fluoropyridinium salt, and a disiloxane reagent. This method, which was carried out at room temperature (or 0 °C), afforded three-, five-, six-, and seven-membered ring nitrogen-containing heterocyclic compounds and was compatible with diverse functional groups.
- Shigehisa, Hiroki,Koseki, Natsumi,Shimizu, Nao,Fujisawa, Mayu,Niitsu, Makoto,Hiroya, Kou
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supporting information
p. 13534 - 13537
(2015/02/02)
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- Tataricins A and B, two novel cyclotetrapeptides from Aster tataricus, and their absolute configuration assignment
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Two novel cyclotetrapeptides, tataricins A and B, with a unique cyclopeptide backbone and aδ 2,4Pro side chain, were isolated from the traditional Chinese medicine Aster tataricus. Their structures and absolute configurations were determined using a combination of spectroscopic data, the advanced Marfey's method, and a total synthesis. Copyright
- Xu, Hui-Min,Yi, Hua,Zhou, Wen-Bing,He, Wen-Jun,Zeng, Gang-Zhi,Xu, Wen-Yan,Tan, Ning-Hua
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supporting information
p. 1380 - 1383
(2013/04/23)
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- 2 - BENZYL, 3 - (PYRIMIDIN- 2 -YL) SUBSTITUTED PYRAZOLES USEFUL AS SGC STIMULATORS
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2-Benzyl, 3 - (pyrimidin- 2 -YL) substituted pyrazoles are described. They are useful as stimulators of sGC, particularly NO - independent, heme - dependent stimulators. These compounds may be useful for treating, preventing or managing various disorders that are herein disclosed.
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Page/Page column 175-176
(2013/07/19)
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- ISOINDOLONE DERIVATIVES
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The present invention provides for compounds of formula (I) wherein A, Y, J, R1, R2, and R3 have any of the values defined therefor in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, diabetes, obesity, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula I.
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Paragraph 0325
(2013/11/05)
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- ISOINDOLONE DERIVATIVES
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Provided are compounds of formula (I), wherein A, Y, J, R1, R2, and R3 have any of the values defined therefor in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, diabetes, obesity, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).
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Page/Page column 64
(2013/11/05)
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- DERIVATIVES OF 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOLS AS PHOSPHODIESTERASE INHIBITORS
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Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols according to formula (I) are useful as inhibitors of the phosphodiesterase 4 (PDE4) enzyme.
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Paragraph 0276; 0277
(2014/01/07)
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- DERIVATIVES OF 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOLS AS PHOSPHODIESTERASE INHIBITORS
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The invention relates to inhibitors of the phosphodiesterase 4 (PDE4) enzyme. More particularly, the invention relates to compounds that are derivatives of 1 -phenyl-2-pyridinyl alkyl alcohols, methods of preparing such compounds, compositions containing them and therapeutic use thereof.
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Page/Page column 55
(2014/01/08)
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- PYRIDINONE AND PYRIDAZINONE DERIVATIVES
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Compounds of formula (I) wherein A1, A2, A3, A4, J, L, G, and R1 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, diabetes, obesity, cancer, and AIDS are disclosed. Pharmaceutical compositions comprising one or more compounds of formula (I) also are disclosed.
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Page/Page column 142
(2014/01/08)
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- Armeniaspiroles, a new class of antibacterials: Antibacterial activities and total synthesis of 5-chloro-Armeniaspirole A
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Armeniaspiroles, a novel class of natural products isolated from Streptomyces armeniacus, are characterized by a novel spiro[4.4]non-8-ene scaffold. Various derivatives of Armeniaspiroles could be obtained by halogenation, alkylation, addition/elimination
- Couturier, Cedric,Bauer, Armin,Rey, Astrid,Schroif-Dufour, Cosima,Broenstrup, Mark
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p. 6292 - 6296
(2012/10/29)
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- Synthesis of 6-substituted 2-pyrrolyl and indolyl benzoxazoles by intramolecular O-arylation in photostimulated reactions
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The synthesis of a series of 6-substituted 2-pyrrolyl and 2-indolyl benzoxazoles by photostimulated C-O cyclization of anions from 2-pyrrole carboxamides, 2-indole carboxamides, or 3-indole carboxamides has been found to proceed in good to excellent yields (41-100%) in DMSO and liquid ammonia. The pyrrole and indole carboxamides are obtained in good to very good isolated yields by an amidation reaction of different 2-haloanilines with 2-carboxylic acid of pyrrole and 2- or 3-carboxylic acid of indole. To explain the regiochemical outcome of these reactions (C-O arylation vs C-N or C-C arylation), a theoretical analysis was performed using DFT methods and the B3LYP functional.
- Vaillard, Victoria A.,Guastavino, Javier F.,Buden, Maria E.,Bardagi, Javier I.,Barolo, Silvia M.,Rossi, Roberto A.
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experimental part
p. 1507 - 1519
(2012/03/11)
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- Pyrrolotriazinone derivatives as PI3K inhibitors
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New pyrrolotriazinone derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Phosphoinositide 3-Kinases (PI3Ks)
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Page/Page column 43
(2012/11/13)
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- Design, synthesis and antifungal activities of novel pyrrole alkaloid analogs
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A series of novel analogs of pyrrole alkaloid were designed and synthesized by a facile method and their structures were characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS). The structure of compound 2a was identified by 2D NMR including heteronuclear multiple-quantum coherence (HMQC), heteronuclear multiple-bond correlation (HMBC) and H-H correlation spectrometry (H-H COSY) spectra. Their antifungal activities against five fungi were evaluated, and the results indicated that some of the title compounds showed moderate fungicidal activities in vitro against Alternaria solani, Cercospora arachidicola, Fusarium omysporum, Gibberella zeae and Physalospora piricola at the dosage of 50 μg mL -1. Compound 2a and 3a exhibited good activities against P. piricola at low dosage.
- Wang, Ming-Zhong,Xu, Han,Liu, Tuan-Wei,Feng, Qi,Yu, Shu-Jing,Wang, Su-Hua,Li, Zheng-Ming
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p. 1463 - 1472
(2011/05/04)
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- 5,5-Diaryldipyrromethanes: Syntheses and anion binding properties
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A two-step synthesis of 5,5-diaryldipyrromethanes in good yields is described. The adopted synthetic strategy can be used to tune the substituent at the meso-carbon very easily by choosing the Grignard reagent of interest. Further, the influence of the in
- Gowri Sreedevi,Thomas, Ajesh P.,Salini,Ramakrishnan,Anju,Derry Holaday,Reddy,Suresh,Srinivasan
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scheme or table
p. 5995 - 5999
(2011/11/28)
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- Diversity-oriented approach to pyrrole-imidazole alkaloid frameworks
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An exploration of imidazolylpropargyl amides as linchpin synthons for the construction of a diverse array of heterocyclic frameworks, many of which are related to those found in the oroidin derived alkaloids, is described. One such intermediate has been u
- Bhandari, Manojkumar R.,Yousufuddin, Muhammed,Lovely, Carl J.
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supporting information; experimental part
p. 1382 - 1385
(2011/05/02)
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- Parameters for bromination of pyrroles in bromoperoxidase-catalyzed oxidations
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Ester-, cyano-, and carboxamide-substituted 1H-pyrroles undergo electrophilic aromatic bromination, if treated with hydrogen peroxide and sodium bromide at pH 6.2 and 20 °C. Oxidation of bromide under such conditions is catalyzed by a vanadate(V)-dependent bromoperoxidase, in a substrate/enzyme ratio of 32-63 μmol %. To obtain maximum yields of bromopyrroles (up to 91%) by spending least amount of substrates and catalyst, hydrogen peroxide and sodium bromide have to be added continuously to the enzyme and the 2-acceptor-substituted pyrrole (1.5 mmol) in a solution of morpholine-4- ethanesulfonic acid buffer. This technique was applied to prepare two marine natural products under biomimetic conditions, that is, methyl 4,5-dibromopyrrole-2-carboxylate (from Agelas oroides) and 4,5-dibromopyrrole-2- carboxamide (from Acanthella carteri).
- Wischang, Diana,Hartung, Jens
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supporting information; experimental part
p. 4048 - 4054
(2011/06/27)
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- Synthesis of pyrrole and indole quinoxalinone and oxazinone derivatives by intramolecular copper-catalyzed reactions
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Intramolecular N-arylation of pyrrole and indole carboxamides and carboxylates linked with a pendant haloarene by Cu-catalyzed reactions to synthesize pyrrole and indole quinoxalinone and oxazinone derivatives is reported. The ring closure reactions were carried out by conventional heating and MW irradiation. The use of conventional heating affords moderate to good yields of the quinoxalinone and oxazinone derivatives (34-72%), while by using MW heating the best results are obtained (41-99%). The Royal Society of Chemistry 2011.
- Vaillard, Victoria A.,Rossi, Roberto A.,Martin, Sandra E.
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experimental part
p. 4927 - 4935
(2011/08/06)
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- Conformational effects in diastereoselective aryne diels-alder reactions: synthesis of benzo-fused [2.2.1] heterobicycles
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It was found that the diastereoselectivity of the Dials-Alder reaction between arynes and substituted furans Is highly sensitive to substitution, which affects the reactive conformation. By varying the location of the groups on the diene partner, It Is po
- Webster, Robert,Lautens, Mark
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supporting information; experimental part
p. 4688 - 4691
(2009/12/26)
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- Synthesis of heteroaromatic tropeines and heterogeneous binding to glycine receptors
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Heteroaromatic carboxylic esters of (nor)tropine were synthesized. Tropine esters displaced [3H]strychnine binding to glycine receptors of rat spinal cord with low Hill slopes. Two-site displacement resulted in nanomolar IC50,1 and m
- Maksay, Gabor,Vincze, Zoltan,Nemes, Peter
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experimental part
p. 6872 - 6878
(2009/12/24)
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- Synthesis of novel fused azaheterocycles by photostimulated intramolecular SRN1 reactions with nitrogen nucleophiles
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The synthesis of pyrrole, indole, and pyrazole fused azaheterocycles is presented. The anions of carboxamides (6 and 12) and pyrazolylamines (15a-b) react under photostimulation by an intramolecular SRN1 process to yield fused azaheterocycles w
- Vaillard, Victoria A.,Budén, María E.,Martín, Sandra E.,Rossi, Roberto A.
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supporting information; experimental part
p. 3829 - 3832
(2009/10/11)
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- PHARMACEUTICAL COMPOSITIONS
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This invention relates to novel pharmaceutical compositions comprising therapeutically effective combination of a positive allosteric modulator of nicotine receptors; and a cognitive enhancer selected from the group consisting of a nicotine acetylcholine
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Page/Page column 13
(2008/06/13)
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- Electron-rich heteroaroylphosphonates and their reaction with trimethyl phosphite
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Dialkyl heteroaroylphosphonates based on thiophene, pyrrole or furan have been prepared and their reactions with trimethyl phosphite investigated. Deoxygenation of the carbonyl groups in these heteroaroylphosphonates occurs to give carbene intermediates, which then undergo further reaction. In the case of the furan-3-oylphosphonates and those systems containing a thiophene or pyrrole ring, the major reaction pathway involves intermolecular trapping of the carbene intermediates by the trimethyl phosphite, leading to the formation of ylidic phosphonates that can be readily converted into the corresponding 1,1-bisphosphonates. However, in some furan-2-oylphosphonates the carbenes generated undergo ring-opening to initially give acyclic alkynylphosphonates which may react further to give other novel phosphorus compounds. The effects of substituents on the extent to which intermolecular trapping of the initially formed carbene competes with intramolecular rearrangement has been investigated. The latter process appears to be suppressed by a substituent at the 5-position of the furan ring, the resulting ylidic phosphonates being a rare example of an efficient intermolecular trapping of a furan-2-yl carbene. The Royal Society of Chemistry 2008.
- Griffiths, D. Vaughan,Al-Jeboori, Mohamad J.,Cheong, Yuen-Ki,Duncanson, Philip,Harris, Jayne E.,Salt, Michael C.,Taylor, Helen V.
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supporting information; experimental part
p. 577 - 585
(2008/10/09)
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- 1H-THIENO[2,3-C]PYRAZOLE COMPOUNDS USEFUL AS KINASE INHIBITORS
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There are provided thieno[2,3-c]pyrazole derivatives of formula (I), wherein A is an aryl or heteroaryl ring, on which the substituent -NHZR5 is at the ortho position to the CONH linker; R1 and R2 are the same or different
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Page/Page column 36
(2008/06/13)
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- Design, synthesis, and evaluation of inhibitors for severe acute respiratory syndrome 3C-like protease based on phthalhydrazide ketones or heteroaromatic esters
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The 3C-like protease (3CLpro), which controls the severe acute respiratory syndrome (SARS) coronavirus replication, has been identified as a potential target for drug design in the treatment of SARS. A series of tetrapeptide phthalhydrazide ketones, pyridinyl esters, and their analogs have been designed, synthesized, and evaluated as potential SARS 3CLpro inhibitors. Some pyridinyl esters are identified as very potent inhibitors, with IC50 values in the nanomolar range (50-65 nM). Electrospray mass spectrometry indicates a mechanism involving acylation of the active site cysteine thiol for this class of inhibitors.
- Zhang, Jianmin,Pettersson, Hanna I.,Huitema, Carly,Niu, Chunying,Yin, Jiang,James, Michael N. G.,Eltis, Lindsay D.,Vederas, John C.
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p. 1850 - 1864
(2008/02/02)
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- Synthesis of substituted heterocyclic compounds
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The invention relates to a method of synthesizing heterocyclic compounds. The invention is characterised in that it consists in opening a compound having formula (I), wherein: —X represents NH, O, S or a N-p group, p being a protective group, such as Boc
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Page/Page column 10
(2008/06/13)
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- SUBSTITUTED PYRROLO-PYRAZOLE DERIVATIVES ACTIVE AS KINASE INHIBITORS
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Substituted pyrrolo-pyrazole derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and 5 pharmaceutical compositions comprising them are disclosed; the compounds of the inv
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Page/Page column 70-71
(2008/06/13)
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- 1H-FURO[3,2-C] PYRAZOLE COMPOUNDS USEFUL AS KINASE INHIBITORS
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Furo[3,2-c]pyrazole derivatives of formula (I) as defined in the description, and pharmaceutically acceptable salts thereof, wherein A is an aryl or heteroaryl ring, - NHZR5 is at the ortho position to the CONH linker; - R1 and Rsub
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Page/Page column 34-35
(2008/06/13)
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- Heterocyclic analogs of?benzanilide derivatives as?potassium channel activators. IX
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On the basis of our previous works, addressed to synthesise new activators of BK potassium channels, and of many suggestions from the international literature, a simple pharmacophoric model, consisting of two suitably substituted phenyl rings bound to var
- Calderone, Vincenzo,Fiamingo, Francesca Lidia,Giorgi, Irene,Leonardi, Michele,Livi, Oreste,Martelli, Alma,Martinotti, Enrica
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p. 761 - 767
(2007/10/03)
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- NOVEL OXADIAZOLE DERIVATIVES AND THEIR MEDICAL USE
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This invention relates to novel oxadiazole derivatives of formula (I) which are found to be modulators of the nicotinic acetylcholine receptors. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of disease
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Page/Page column 18
(2008/06/13)
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- A valuable synthesis of pyrrolo[1,2-a]quinoxalines, indolo[1,2-a] quinoxalines and their aza-analogues by palladium-catalyzed intramolecular carbon-nitrogen bond formation
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A novel and efficient method for the construction of pyrrolo[1,2-a] quinoxalines, indolo[1,2-a]quinoxalines and their aza-analogues is described. The reaction involves a Pd-catalyzed intramolecular cyclization as the key step and provides the desired prod
- Abbiati, Giorgio,Beccalli, Egle M.,Broggini, Gianluigi,Paladino, Giuseppe,Rossi, Elisabetta
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p. 2881 - 2886
(2007/10/03)
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- Anthranilic acid based CCK1 antagonists: The 2-indole moiety may represent a "needle" according to the recent homonymous concept
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Recently we described an innovative class of non-peptide CCK1 antagonists keeping appropriate pharmacophoric groups on the anthranilic acid employed as a molecular scaffold. The lead compound obtained, VL-0395, characterized by the presence of Phe and the 2-indole moiety at the C- and N-termini of anthranilic acid, respectively, is endowed with submicromolar affinity towards CCK1 receptors. Thus, we have prepared and tested on CCK receptors a library of VL-0395 analogues in order to investigate the precise topological and essential key interactions of the 2-indole group of the lead with the CCK1 receptor. The obtained results confirm that this group establishes very specific interactions with this receptor sub-site and may be viewed as a "needle" group.
- Varnavas, Antonio,Lassiani, Lucia,Valenta, Valentina,Berti, Federico,Tontini, Andrea,Mennuni, Laura,Makovec, Francesco
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- 3-PYRROLYL-PYRIDOPYRAZOLES AND 3-PYRROLYL-INDAZOLES AS NOVEL KINASE INHIBITORS
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Compounds of Formula (I) are useful as mediators of protein kinases and have activity as cell proliferation inhibitors where X, R1-R7 and R9 are as defined herein.
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Page/Page column 78
(2010/02/06)
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- Spiro compounds or salts thereof and preventives/remedies for autoimmune diseases and AP-1 inhibitors containing the same
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The spiro compounds of the present invention represented by the general formula: wherein A, R2, R3, R4, R5, R6and n are as defined in the specification, exhibit an AP-1 activity inhibitory action and, based on the AP-1 inhibitory action, suppresses the expression of a wide variety of genes and are useful as an agent for treating and preventing autoimmune diseases with lessoned side reactions.
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- Synthesis of milbemycins alpha9, alpha10, alpha11, alpha12, alpha14, alpha15, alpha20, alpha21, alpha22, alpha23, alpha26, alpha27, delta(2,3),delta(4,26)-milbemycins A3, A4 from milbemycins A3, A4, and their acaricidal activities.
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Chemical derivation methods to prepare 26-acyloxy and 26-hydroxymilbemycins, which had been reported as natural products, milbemycins alpha9, alpha10, alpha11, alpha12, alpha14, alpha15, alpha20, alpha21, alpha22, alpha23, alpha26, alpha27 from milbemycins A3, A4 were reported. Delta(2,3),delta(4,26)-milbemycins A3, A4, which had also been reported as natural products, were further prepared from milbemycins A3, A4. Their acaricidal activities were also assessed against the organophosphorus-sensitive two-spotted spider mite (Tetranychus urticae) on primary leaves of cowpea plants (Vigna sinesis Savi species) by spraying.
- Tsukiyama, Takahiro,Kajino, Hisaki,Kajino, Fumie,Furuta, Satoru,Tsukamoto, Yoshihisa,Sato, Kazuo,Kinoshita, Ayako,Ichinose, Reiji,Tanaka, Keiji
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p. 993 - 1003
(2007/10/03)
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