- Intramolecular carbenoid insertions into thiophene: Reactions of 1-diazo-3-(2-thienyl)-2-propanone and 1-diazo-3-(3-thienyl)-2-propanone
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Treatment of 1-diazo-3-(2-thienyl)-2-propanone with catalytic rhodium (II) acetate results in cyclopropanation followed by acid-catalyzed ring opening and tautomerization to yield 5,6-dihydro-4H-cyclopenta[b]thiophen-5-one. Under the same conditions, however, the isomecic 1-diazo-3-(3-thienyl)-2-propanone generates a cyclopropane intermediate which undergoes [4+2] cycloreversion, isomerization and Diels-Alder dimerization to give a complex spiro-disulphide. While the 2-substituted thiophene behaves like other homologous members of the thienyl series, the isomeric 3-substituted thiophene undergoes chemistry seen previously with analogous furanyl compounds. The insight into the mechanistic underpinnings provided by preliminary molecular modeling at a PM3 level is discussed.
- Frampton, Christopher S.,Pole, David L.,Yong, Kelvin,Capretta, Alfredo
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Read Online
- Method for efficiently preparing thiophene medical intermediates
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The invention belongs to the field of synthesis of thiophene medical intermediates, discloses a method for efficiently preparing the thiophene medical intermediates, and particularly discloses a process for synthesizing 2-thiopheneacetic acid from 2-thiopheneethanol through a catalytic reaction, catalyzing the 2-thiopheneacetic acid to generate a 2-thiopheneacetyl chloride crude product and then purifying the 2-thiopheneacetyl chloride crude product. The reaction conditions are mild, the product purity is high, the synthesis efficiency is high, and the yield reaches 90% or above.
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Paragraph 0014-0019
(2021/05/29)
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- A Simple and Efficient Synthesis of Fused Benzo[ b ]thiophene Derivatives
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A new approach to the synthesis of fused benzothiophene derivatives was developed based on iodine-promoted photocyclization of 4,5-diaryl-substituted thiophenes obtained in three steps from commercially available compounds. Comparative analysis showed that photochemical cyclization is a more efficient method for the preparation of fused benzo[ b ]thiophene derivatives, compared to oxidative coupling of 4,5-diaryl-substituted thiophenes in the presence of iron(III) chloride and palladium-catalyzed intramolecular arylation. This new approach provides an efficient synthesis of functionally substituted naphtho[2,1- b:3,4- b ′]dithiophenes, phenanthro[9,10- b ]thiophenes, benzo[1,2- b:3,4- b ′:6,5- b ′′]trithiophenes, as well as new fused heterocycles containing a pyridine ring and/or a carbazole moiety.
- Ulyankin, Evgeny B.,Kostyuchenko, Anastasia S.,Chernenko, Sergey A.,Bystrushkin, Mikhail O.,Samsonenko, Anna L.,Shatsauskas, Anton L.,Fisyuk, Alexander S.
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p. 2422 - 2434
(2021/04/21)
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- Preparation method of 2-thiopheneacetyl chloride
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The invention discloses a preparation method of 2-thiopheneacetyl chloride, and belongs to the technical field of chemical synthesis. The preparation method comprises the following steps: (1) dissolving 2-thiopheneethanol in an organic solvent, and reacting at 50-120 DEG C under the action of a solid acid catalyst, an alkali and an oxidant to prepare 2-thiopheneacetic acid, wherein the oxidant isoxygen or hydrogen peroxide; and (2) dissolving 2-thiopheneacetic acid in an organic solvent, and dropwise adding thionyl chloride to carry out an acylating chlorination reaction by taking an alkalineionic liquid as a catalyst so as to prepare 2-thiopheneacetyl chloride. The preparation method is simple in route, easy in obtaining of raw materials, mild in reaction conditions, and capable of realizing few byproducts and easy purification and separation due to adoption of oxygen or hydrogen peroxide as the oxidant in synthesis of 2-thiopheneacetic acid; and when the acylating chlorination reaction of 2-thiopheneacetic acid is carried out, the basic ionic liquid is adopted as the catalyst, the reaction process is stable and easy to control, the product yield is high, few byproducts are produced, so the method is an efficient and green synthesis process.
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Paragraph 0034; 0038-0041; 0044-0046; 0049-0051; 0054-0056
(2020/08/30)
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- One-pot method for the synthesis of 1-aryl-2-aminoalkanol derivatives from the corresponding amides or nitriles
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We have identified a novel one-pot method for the synthesis of β-amino alcohols, which is based on C-H bond hydroxylation at the benzylic α-carbon atom with a subsequent nitrile or amide functional group reduction. This cascade process uses molecular oxygen as an oxidant and sodium bis(2-methoxyethoxy)aluminum hydride as a reductant. The substrate scope was examined on 30 entries and, although the respective products were provided in moderate yields only, the above simple protocol may serve as a direct and powerful entry to the sterically congested 1,2-amino alcohols that are difficult to prepare by other routes. The plausible mechanistic rationale for the observed results is given and the reaction was applied to a synthesis of a potentially bioactive target. This journal is
- Bobal, Pavel,Otevrel, Jan,Svestka, David
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p. 25029 - 25045
(2020/07/14)
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- Design, synthesis and agricultural evaluation of derivatives of N-Acyl-N-(m-fluoro-benzyl)-6-amino-coumarin
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ABTRACT: This study aims to design and synthesize a series of N-Acyl-N-(m-fluoro- benzyl)-6- amino-coumarins through the principle of active substructure stitching, which are based on the core structure of N-(m-fluoro-benzyl)-6-amino-coumarin. The structures of target compounds e1–e25 have been characterized by 1H NMR, 13C NMR, ESI-MS and elemental analysis. Meanwhile, their agricultural activity have been evaluated in two weeds (Amaranth and Crabgrass) and four widespread noxious pathogens (V.mali, B.cinerea, F.axysporium and C.bacteria). The herbicidal activity results showed that almost all synthetic molecules have a greater impact on the stem system than on the root. Excellent inhibition rates were discovered from compounds e2–e5 and e20–e23 against Amaranth on stems, which were above 58percent(20 mg/L), 68percent(100 mg/L) respectively. Compounds e2 and e21 also exhibited striking inhibition on stems growth of both weeds. Anti-pathogenic activity showed that all the compounds exerted a better inhibitory activity on B.cinerea at 20 ppm compared to control carbendazim. All the heterocyclic substituted compounds (e17–e24, >57percent) made a better influence than the control (54.1percent) at the100 ppm. This research provides promising herbicidal and anti-pathogenic agents that have the better effects and can be potential for further development.
- Ding, Yin-hao,Dong, Jing-jing,Feng, Bai-cheng,Hao, Shuang-hong,Jin, Yan,Wei, Yan
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supporting information
(2020/08/19)
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- Palladium-Catalyzed Distal C?H Selenylation of 2-Aryl Acetamides with Diselenides and Selenyl Chlorides
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A convenient and effective method of palladium-catalyzed C?H selenylation of the 2-aryl acetamides assisted with removable 8-aminoquinoline with readily available diselenides and selenyl chlorides has been developed. This selenylation reaction is scalable and tolerates a wide range of functional groups, providing a straightforward way of the preparing unsymmetrical diaryl selenides and dibenzoselene-pinone. Preliminary mechanistic studies indicated that a single-electron transfer type mechanism and facile C?H metalation are operative. (Figure presented.).
- Gu, Linghui,He, Meicui,Ma, Wenbo,Tan, Yuqiang,Wang, Yang,Wang, Yuchi,Zhang, Chunran
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supporting information
p. 5708 - 5715
(2020/12/01)
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- Regio- and Enantioselective Formal Hydroamination of Enamines for the Synthesis of 1,2-Diamines
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The asymmetric formal hydroamination of enamines using a CuH catalyst is reported. The method provides a straightforward and efficient approach to the synthesis of chiral 1,2-dialkyl amines in good yields with high levels of enantioselectivities for a broad range of substrates, and should have significant value for the preparation of molecules bearing a 1,2-diamine motif.
- Yu, Lu,Somfai, Peter
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supporting information
p. 8551 - 8555
(2019/05/21)
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- Electrochemical Difluoromethylarylation of Alkynes
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An unprecedented radical difluoromethylarylation reaction of alkynes has been developed by discovering a new difluoromethylation reagent, CF2HSO2NHNHBoc. This air-stable and solid reagent can be prepared in one step from commercially available reagents CF2HSO2Cl and NH2NHBoc. The CF2H radical, generated through ferrocene-mediated electrochemical oxidation, participates in an unexplored alkyne addition reaction followed by a challenging 7-membered ring-forming homolytic aromatic substitution step to afford fluorinated dibenzazepines.
- Xiong, Peng,Xu, He-Huan,Song, Jinshuai,Xu, Hai-Chao
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supporting information
p. 2460 - 2464
(2018/02/28)
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- Directed Remote Lateral Metalation: Highly Substituted 2-Naphthols and BINOLs by In Situ Generation of a Directing Group
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A general synthesis of highly substituted 2-naphthols based on a new carbanionic reaction sequence is demonstrated. The reaction exploits the dual nature of lithium bases consisting of consecutive ring opening of readily available coumarins with either LiNEt2 or LiNiPr2 into Z-cinnamamides, thus generating a directing group in situ and allowing, by conformational freedom, a lateral directed remote metalation for ring closure to give the aryl 2-naphthols in good to excellent yields. These transformations can be combined to provide a more efficient one-pot process. Mechanistic insight into the remote lateral metalation step, demonstrating the requirement of Z-cinnamamide, is described. Application of this methodology to the synthesis of highly substituted 3,3′-diaryl BINOL ligands is also reported.
- Patel, Jignesh J.,Laars, Marju,Gan, Wei,Board, Johnathan,Kitching, Matthew O.,Snieckus, Victor
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supporting information
p. 9425 - 9429
(2018/07/29)
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- Synthesis and peripheral substituent effects of bay-annulated indigo derivatives
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In this study, indolo-naphthyridine-6,13-diones (5a–d) with four different peripheral substituents were prepared via bay-annulation reactions of indigo. The resulting compounds (5a–d) exhibited fluorescence in the red to near-IR region, while the parent indigo molecule showed no fluorescence. Although the peripheral substituents were oriented to the exterior of the π-conjugated system, the electronic structure affected the absorption and fluorescence spectra. Moreover, calculated molecular orbitals and absorption spectra successfully reproduced the experimental absorption spectra and cyclic voltammograms.
- Furuyama, Taniyuki,Tamura, Daichi,Maeda, Hajime,Segi, Masahito
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p. 2913 - 2916
(2018/06/25)
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- Compounding method for 2-thiopheneacetyl chloride
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The invention discloses a compounding method for 2-thiopheneacetyl chloride and belongs to the technical field of organic synthesis. The 2-thiopheneacetyl chloride is compounded by taking thiophene asa raw material through following three-step reaction: 1) acquiring 2-thiophene acetate through the F-C reaction of thiophene and glycolate under the existence of catalyst; 2) hydrolyzing the 2-thiophene acetate under the existence of acid, thereby acquiring 2-thiopheneacetic acid; 3) treating the 2-thiopheneacetic acid in the manner of acylating chlorination with thionyl chloride under the catalysis of pyridine, thereby acquiring 2-thiopheneacetyl chloride. The compounding method for 2-thiopheneacetyl chloride has the characteristics of easily acquired raw materials and simple and convenientoperation and is suitable for industrial production.
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Paragraph 0042; 0047; 0048; 0054; 0055
(2019/01/06)
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- Preparation method of 2-thiopheneacetyl chloride
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The invention relates to a preparation method of 2-thiopheneacetyl chloride. The preparation method comprises the following steps: dissolving 2-thiopheneacetic acid into dichloromethane, then adding a catalyst, cooling to the temperature ranging from -10 DEG C to 0 DEG C, dropwise adding dichloromethane solution of trichloromethyl carbonate, then heating to 0-10 DEG C, carrying out heat preservation and reacting for 5-10 hours, distilling off dichloromethane, and carrying out reduced pressure distillation, so that the product 2-thiopheneacetyl chloride is obtained. The preparation method provided by the invention has the positive effects that firstly strong oxidization characteristic of thionyl chloride is avoided, and trichloromethyl carbonate is adopted, so that reaction is more fully, reaction yield is increased, and reaction cost is reduced; secondly, trichloromethyl carbonate is adopted as a reaction raw material, carbon dioxide and hydrogen chloride gases are eliminated during reaction, tail gas is absorbed by caustic soda liquid, and then no pollution is produced to the atmosphere; and (3) raw materials are available, technology is simple and reasonable, and no wastewater is produced in the whole process. Compared with the traditional production technology, the preparation method provided by the invention has obvious economic benefit and environmental benefit.
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Paragraph 0010; 0018-0025
(2017/09/01)
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- Development of [18F]Maleimide-Based Glycogen Synthase Kinase-3β Ligands for Positron Emission Tomography Imaging
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Dysregulation of glycogen synthase kinase-3β (GSK-3β) is implicated in the pathogenesis of neurodegenerative and psychiatric disorders. Thus, development of GSK-3β radiotracers for positron emission tomography (PET) imaging is of paramount importance, because such a noninvasive imaging technique would allow better understanding of the link between the activity of GSK-3β and central nervous system disorders in living organisms, and it would enable early detection of the enzyme’s aberrant activity. Herein, we report the synthesis and biological evaluation of a series of fluorine-substituted maleimide derivatives that are high-affinity GSK-3β inhibitors. Radiosynthesis of a potential GSK-3β tracer [18F]10a is achieved. Preliminary in vivo PET imaging studies in rodents show moderate brain uptake, although no saturable binding was observed in the brain. Further refinement of the lead scaffold to develop potent [18F]-labeled GSK-3 radiotracers for PET imaging of the central nervous system is warranted.
- Hu, Kongzhen,Patnaik, Debasis,Collier, Thomas Lee,Lee, Katarzyna N.,Gao, Han,Swoyer, Matthew R.,Rotstein, Benjamin H.,Krishnan, Hema S.,Liang, Steven H.,Wang, Jin,Yan, Zhiqiang,Hooker, Jacob M.,Vasdev, Neil,Haggarty, Stephen J.,Ngai, Ming-Yu
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supporting information
p. 287 - 292
(2017/03/17)
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- A novel complexity-to-diversity strategy for the diversity-oriented synthesis of structurally diverse and complex macrocycles from quinine
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Recent years have witnessed a global decline in the productivity and advancement of the pharmaceutical industry. A major contributing factor to this is the downturn in drug discovery successes. This can be attributed to the lack of structural (particularly scaffold) diversity and structural complexity exhibited by current small molecule screening collections. Macrocycles have been shown to exhibit a diverse range of biological properties, with over 100 natural product-derived examples currently marketed as FDA-approved drugs. Despite this, synthetic macrocycles are widely considered to be a poorly explored structural class within drug discovery, which can be attributed to their synthetic intractability. Herein we describe a novel complexity-to-diversity strategy for the diversity-oriented synthesis of novel, structurally complex and diverse macrocyclic scaffolds from natural product starting materials. This approach exploits the inherent structural (including functional) and stereochemical complexity of natural products in order to rapidly generate diversity and complexity. Readily-accessible natural product-derived intermediates serve as structural templates which can be divergently functionalized with different building blocks to generate a diverse range of acyclic precursors. Subsequent macrocyclisation then furnishes compounds that are each based around a distinct molecular scaffold. Thus, high levels of library scaffold diversity can be rapidly achieved. In this proof-of-concept study, the natural product quinine was used as the foundation for library synthesis, and six novel structurally diverse, highly complex and functionalized macrocycles were generated.
- Ciardiello,Stewart,Sore,Galloway,Spring
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p. 2825 - 2843
(2017/05/29)
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- Carboxamides as N-Alkylating Reagents of Secondary Amines in Indium-Catalyzed Reductive Amination with a Hydrosilane
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A method for the catalytic reductive N-alkylation of amines by using secondary amides as the alkyl source was developed. A versatile type of carboxamide functioned as an N-alkylation reagent in the presence of an indium(III) catalyst and a hydrosilane to provide alkylated tertiary amines efficiently. This amide-based catalytic N-alkylation strategy is considered to be a highly useful protocol to access unsymmetrical tertiary amines.
- Ogiwara, Yohei,Shimoda, Wataru,Ide, Keisuke,Nakajima, Takumi,Sakai, Norio
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supporting information
p. 2866 - 2870
(2017/06/06)
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- Method for preparing acyl chloride by catalyzing phosgene and acid
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The invention discloses a method for preparing acyl chloride by catalyzing phosgene and acid. The method includes the following steps that 1, with carboxylic acid as a raw material, a catalyst and a solvent are added, and under the condition that the temperature is maintained to range from 20 DEG C to 200 DEG C, phosgene is introduced into a reaction flask for a reaction; 2, after the molar ratio of carboxylic acid to phosgene reaches 1:1.0-1:10, phosgene introduction is stopped, reacted mixed liquor is obtained and filtered, obtained filter liquor is subjected to reduced pressure distillation at a high vacuum degree to obtain acyl chloride, and an obtained filter cake continues to serve as the catalyst in the step 1 to be recycled. Compared with an existing catalyst adopted for preparing acyl chloride according to a phosgene method, the catalyst used in the method is small in dosage, convenient to recycle, easy to separate from a product, better in product quality, safe, stable and environmentally friendly, generated solid waste is greatly reduced, the experience of operators is greatly improved, and safety risks are lowered.
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Paragraph 0076; 0077; 0078
(2016/10/20)
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- Preparation method of acyl chloride
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The invention relates to a preparation method of acyl chloride. The method comprises the following steps that 1, carboxylic acid is added into a reactor, or carboxylic acid is dissolved in organic solvent, a device is connected, and the temperature is raised to 100 DGE C-250 DEG C; 2, phosgene is introduced into the reactor for a reaction, and then the temperature is decreased to room temperature; 3, nitrogen is introduced, residual phosgene and hydrogen chloride are cleaned away, reaction liquid which is reacted without solvent is subjected to decompression distillation and purification directly, and needed acyl chloride is obtained; reaction liquid which is reacted with the solvent is subjected to decompression distillation to remove the solvent, and needed acyl chloride is obtained. According to the preparation method of acyl chloride, no catalyst is added, the risks that in the synthesizing process, due to the fact that the catalyst is dissolved, color of the finial product of acyl chloride is increased, and the catalyst is remained in late products are avoided, after the reaction is finished, high-quality acyl chloride can be obtained through decompression distillation, and the technological process is simple; due to the fact that in the whole technological process, except for absorbable and available phosgene, hydrogen chloride and carbon dioxide, no other three waste is discharged, the preparation method of acyl chloride is environmentally friendly, and the good implement value is achieved.
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Paragraph 0064; 0065
(2016/11/28)
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- TRIFLUOROMETHOXYLATION OF ARENES VIA INTRAMOLECULAR TRIFLUOROMETHOXY GROUP MIGRATION
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The present invention provides a process of producing a trifluoromethoxylated aryl or trifluoromethoxylated heteroaryl having the structure: (I), wherein A is an aryl or heteroaryl, each with or without subsutitution; and R1 is -H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), - (alkylaryl), - (alkylheteroaryl), -NH-(alkyl), -N(alkyl)2, -NH-(alkenyl), -NH-(alkynyl) -NH-(aryl), -NH-(heteroaryl), -O-(alkyl), -O-(alkenyl), -O-(alkynyl), -O-(aryl), -O-(heteroaryl), -S-(alkyl), -S- (alkenyl), -S-(alkynyl), -S-(aryl), or -S-(heteroaryl), comprising: (a) reacting a compound having the structure: (II), with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure: (III); and (b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure: (I).
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Page/Page column 174-175
(2016/05/02)
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- CuI-catalyzed cycloisomerization of propargyl amides
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The synthesis of substituted dihydrooxazoles by the CuI-catalyzed cycloisomerization of terminal propargyl amides is reported. The reaction has been shown to have good substrate scope and experiments to delineate the mechanism have been performed. Substrates containing a benzylic methylene were oxidized to the ketone under the reaction conditions.
- Alhalib, Ali,Moran, Wesley J.
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p. 795 - 800
(2014/01/23)
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- SERINE RACEMASE INHIBITOR
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A novel serine racemase inhibitor exhibits sufficient activity and specificity. The serine racemase inhibitor includes one or more compounds selected from compounds respectively represented by the following general formulas [MM_1], [DR_1], [DR'_1], [LW_1], and [ED_1] as an active ingredient.
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Paragraph 0176
(2014/12/12)
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- Metal-free aerobic oxidation of benzazole derivatives
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2-Benzyl benzothiazoles and benzimidazoles are easily oxidized under air and basic conditions to give the corresponding ketones in good yields. The use of palladium acetate as a catalyst has little effect and even gives, in some cases, much lower yields.
- Dos Santos, Aurelie,El Kaim, Laurent,Grimaud, Laurence
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supporting information
p. 3282 - 3287
(2013/06/05)
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- Copper(ii) chloride mediated (aza)oxindole synthesis by oxidative coupling of Csp2-H and Csp3-H centers: Substrate scope and DFT study
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A CuCl2 mediated direct intramolecular oxidative coupling of Csp2-H and Csp3-H centers gives access to 3,3-disubstituted oxindoles containing aromatic, heteroaromatic and alkyl substituents as well as a heteroatom at the quaternary center in good to excellent yields. The reaction is carried out in the presence of NaOtBu and CuCl2 in DMF at 110 °C. The key step of this reaction is the formation of an amidyl radical by one electron oxidation of amide enolate followed by an intramolecular radical cyclization reaction (homolytic aromatic substitution reaction). A detailed DFT study shows that the cyclization of the amidyl radical is the rate-limiting step in the oxindole synthesis, whereas the second single electron transfer (SET) becomes the rate-determining step in the aza-oxindole formation. Computational data are in agreement with the experimentally observed relative reactivity and regioselectivity.
- Dey, Chandan,Larionov, Evgeny,Kuendig, E. Peter
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supporting information
p. 6734 - 6743
(2013/10/01)
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- Asymmetric hydrogenation of α- Or β-acyloxy α,β- unsaturated phosphonates catalyzed by a Rh(i) complex of monodentate phosphoramidite
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The Rh(i) complex of a monodentate phosphoramidite bearing a primary amine moiety (DpenPhos) has been disclosed to be highly efficient for the asymmetric hydrogenation of a variety of α- or β-acyloxy α,β- unsaturated phosphonates, providing the corresponding biologically important chiral α- or β-hydroxy phosphonic acid derivatives with excellent enantioselectivities (90->99% ee).
- Zhang, Jinzhu,Dong, Kaiwu,Wang, Zheng,Ding, Kuiling
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supporting information; scheme or table
p. 1598 - 1601
(2012/03/22)
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- Enantioselective activation of stable carboxylate esters as enolate equivalents via N-heterocyclic carbene catalysts
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The first N-Heterocyclic Carbene (NHC) mediated activation of stable carboxylate esters to generate enolate intermediates is disclosed. The catalytically generated arylacetic ester enolates undergo enantioselective reactions with α,β-unsaturated imines.
- Hao, Lin,Du, Yu,Lv, Hui,Chen, Xingkuan,Jiang, Huishen,Shao, Yaling,Chi, Yonggui Robin
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supporting information; experimental part
p. 2154 - 2157
(2012/07/14)
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- Thiophene inhibitors of PDE4: Crystal structures show a second binding mode at the catalytic domain of PDE4D2
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PDE4 inhibitors have been identified as therapeutic targets for a variety of conditions, particularly inflammatory diseases. We have serendipitously identified a novel class of phosphodiesterase 4 (PDE4) inhibitor during a study to discover antagonists of the parathyroid hormone receptor. X-ray crystallographic studies of PDE4D2 complexed to four potent inhibitors reveal the atomic details of how they inhibit the enzyme and a notable contrast to another recently reported thiophene-based inhibitor.
- Nankervis, Jacob L.,Feil, Susanne C.,Hancock, Nancy C.,Zheng, Zhaohua,Ng, Hooi-Ling,Morton, Craig J.,Holien, Jessica K.,Ho, Patricia W.M.,Frazzetto, Mark M.,Jennings, Ian G.,Manallack, David T.,John Martin,Thompson, Philip E.,Parker, Michael W.
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supporting information; experimental part
p. 7089 - 7093
(2012/01/06)
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- NOVEL DIHYDROPYRIMIDIN-2(1H)-ONE COMPOUNDS AS S-NITROSOGLUTATHIONE REDUCTASE INHIBITORS
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The present invention is directed to novel dihydropyrimidin-2(1H)-one compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors, pharmaceutical compositions comprising such compounds, and methods of making and using the same.
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Page/Page column 135
(2011/04/24)
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- Synthesis of selective SRPK-1 inhibitors: Novel tricyclic quinoxaline derivatives
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SR protein-specific kinase-1 (SRPK-1) has been identified as a validated target for hepatitis B virus (HBV). A series of novel tricyclic quinoxaline derivatives was designed and synthesised as potential kinase inhibitory antiviral agents and was found to be active and selective for SRPK-1 kinase. Most of these novel compounds have drug-like properties according to experimentally determined Log P and Log S values.
- Szekelyhidi, Zsolt,Pato, Janos,Waczek, Frigyes,Banhegyi, Peter,Hegymegi-Barakonyi, Balint,Eros, Daniel,Meszaros, Gyoergy,Hollosy, Ferenc,Hafenbradl, Doris,Obert, Sabine,Klebl, Bert,Keri, Gyoergy,Orfi, Laszlo
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p. 3241 - 3246
(2007/10/03)
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- Quinolones as gonadotropin releasing hormone (GnRH) antagonists: Simultaneous optimization of the C(3)-aryl and C(6)-substituents
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A series of 3-arylquinolones was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) antagonists. A variety of substitution patterns of the 3-aryl substituent are described. The 3,4,5-trimethylphenyl substituent (23h) was found to be optimal. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Young, Jonathan R.,Huang, Song X.,Chen, Irene,Walsh, Thomas F.,DeVita, Robert J.,Wyvratt Jr., Matthew J.,Goulet, Mark T.,Ren, Ning,Lo, Jane,Yang, Yi Tien,Yudkovitz, Joel B.,Cheng, Kang,Smith, Roy G.
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p. 1723 - 1727
(2007/10/03)
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- Antagonists of gonadotropin releasing hormone
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PCT No. PCT/US97/08428 Sec. 371 Date Nov. 12, 1998 Sec. 102(e) Date Nov. 12, 1998 PCT Filed May 16, 1997 PCT Pub. No. WO97/44037 PCT Pub. Date Nov. 27, 1997There are disclosed compounds of formula (I) and pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related conditions in both men and women.
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- Antagonists of gonadotropin releasing hormone
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PCT No. PCT/US97/08782 Sec. 371 Date Nov. 12, 1998 Sec. 102(e) Date Nov. 12, 1998 PCT Filed May 16, 1997 PCT Pub. No. WO97/44041 PCT Pub. Date Nov. 27, 1997There are disclosed compounds of formula (I) and pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related conditions in both men and women.
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- Intramolecular Cyclization of Amido Acids into Pyrrolidinothieno(or [1]benzothieno)[3]azepinediones
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The synthesis of pyrrolidino[2,1-b]thieno[3,2(2,3)-f[3]azepinediones 7a,b and pyrrolidino[2,1-b]-[11]benzothieno[3,2(2,3)-f][3]azepinediones 7c,d are described starting from thiophenes or [1]benzothiophenes acetic acids. Their selective reduction using triethylsilane led to the corresponding azepinones 17a-d.
- Othman, Mohamed,Netchitailo, Pierre,Decroix, Bernard
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p. 225 - 231
(2007/10/03)
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- Presynaptic cholinergic modulators as potent cognition enhancers and analgesic drugs. 1. Tropic and 2-phenylpropionic acid esters
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Previous studies have shown that (R)-(+)-hyoscyamine has analgesic activity as a consequence of increased ACh release following antagonism of central muscarinic autoreceptors. Since the enhancement of central cholinergic transmission could be beneficial for cognitive disorders, we manipulated (R)-(+)-hyoscyamine, synthesizing several derivatives of tropic and 2-phenylpropionic acids, with the aim of obtaining drugs which are able to increase ACh release and consequently to show analgesic and nootropic activities. The results showed that several new compounds are indeed potent analgesics (with an analgesic efficacy comparable to that of morphine) and that the most potent one ((±)-19, PG9) also has remarkable cognition- enhancing properties. Our study confirmed that the mechanism of action involves ACh release even if it is still unclear whether only muscarinic autoreceptors or, also, heteroreceptors are involved.
- Gualtieri,Conti,Dei,Giovannoni,Nannucci,Romanelli,Scapecchi,Teodori,Fanfani,Ghelardini,Giotti,Bartolini
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p. 1704 - 1711
(2007/10/02)
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- Structure-activity relationship within a series of pyrazolidinone antibacterial agents. 2. Effect of side-chain modification on in vitro activity and pharmacokinetic parameters
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The structure-activity relationship among a series of novel pyrazolidinone antibacterial agents is described. Specifically, the effect of modification of the side chain attached to the nitrogen at C-7 was explored in an attempt to improve the potency and spectrum of activity. This approach was successful in identifying several compounds having good in vitro profiles. These top candidates were then evaluated for their activity in vivo, and their pharmacokinetic behavior in various animal models was explored. This information proved critical for the identification of candidates for clinical evaluation.
- Ternansky,Draheim,Pike,Counter,Eudaly,Kasher
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p. 3224 - 3229
(2007/10/02)
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- 1-SULFO-2-OXOAZETIDINE DERIVATIVES AND THEIR PRODUCTION
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Disclosed are compounds of the general formula: wherein R1 is amino, an acylated amino or a protected amino group, X is hydrogen or methoxy, and R is hydrogen, R or R4 where R is an organic residue attached to the azetidine ring through a carbon atom therein and R4 is azido, a halogen, an amino group which may optionally be acylated or a group of the formula wherein R5 is an organic residue and n is 0, 1 or 2, and pharmaceutically acceptable salts and esters thereof. The compounds have antimicrobial and/or beta-lactamase-inhibitory activity and are of value as drugs for human beings and domesticated animals
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- 1-SULFO-2-OXOAZETIDINE DERIVATIVES AND THEIR PRODUCTION
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Disclosed are compounds of the general formula: wherein R1 is amino, an acylated amino or a protected amino group, X is hydrogen or methoxy, and R' is hydrogen, R or R4 wherein R is an organic residue attached to the azetidine ring through a carbon atom therein and R4 is azido, a halogen, an amino group which may optionally be acylated or a group of the formula wherein R5 is an organic residue and n is 0, 1 or 2, and pharmaceutically acceptable salts and esters thereof. The compounds have antimicrobial and/or Beta-lactamase-inhibitory activity and are of value as drugs for human beings and domesticated animals
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- BICYCLIC IMIDAZOLIDINONES AS POTENTIAL ANTIBIOTICS
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The bicyclic imidazolidinones 5 topologically related to the penicillin family, are susceptible to form a stable carbamate with serine-D,D-peptidases.A series of N-7 acylated or sulfonylated (2R,5R)-3,3-dimethyl-8-oxo-4-thia-7,1-diazabicyclooctane-2-carboxylates 12-21 have been prepared.None of these novel penicillin analogs exhibited antibacterial activity.
- Marchand-Brynaert, Jacqueline,Vanlierde, Huguette,Ghosez, Leon
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p. 1081 - 1094
(2007/10/02)
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- 1-SULFO-2-OXOAZETIDINE DERIVATIVES AND THEIR PRODUCTION
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Disclosed are compounds of the general formula: wherein R1 is amino, an acylated amino or a protected amino group, X is hydrogen or methoxy, and R" is hydrogen, R or R4 wherein R is an organic residue attached to the azetidine ring through a carbon atom therein and R4 is azido, a halogen, an amino group which may optionally be acylated or a group of the formula ?OR5, or ?S-S-R5 wherein R5 is an organic residue and n is 0, 1 or 2, and pharmaceutically acceptable salts and esters thereof. The compounds have antimicrobial and/or beta-lactamase-inhibitory activity and are of value as drugs for human beings and domesticated animals
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- Antibacterial hydrazono cephalosporins
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Antibacterial cephalosporins of the following formula: STR1 WHEREIN A and B each is a hydrogen or an amino protecting group; X is a hydroxy or a carboxy protecting group; Y is a hydrogen, halogen, alkyl, alkoxy, or an alkylthio; R is a hydrogen or an alkyl; Z is a group of the formula STR2 (in which R1 and R2 are the same or different and are a hydrogen, optionally substituted hydrocarbon group, organic acyl, or a group of the formula STR3 respectively, in which M and M' are the same or different and are an oxygen or sulfur; R3 is a hydrocarbon group; R1 and R2 can be combined together directly or through a hetero atom); m is 0 or 1; and the broken line shows the presence of a double bond at position 2 or 3, preparable from the compounds shown by the above formula in which Z is an oxygen by treatment with a compound shown by the formula H2 Z; and pharmaceuticals containing these compounds.
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- 2-Acyl-3-substituted cyclopentan-1-ones and process for their preparation
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1,3-Dicarbonyl compounds useful as medicines, agricultural chemicals, perfumes, and their intermediates are prepared by reacting a specific α,β-unsaturated carbonyl compound with a specific organic copper lithium compound in the presence of an aprotic inert organic solvent, and then reacting the reaction product with an organic carboxylic acid halide or anhydride. In particular, novel 2-acyl-3-substituted cyclopentan-1-ones and 2-acyl-3-substituted cyclohexan-1-ones having important physiological activities are provided.
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