- Synthesis of methyl 3,6-dioxo-endo-tricyclo[6.2.1.0 2,7]undeca-4,9-diene-2-carboxylate as synthetic intermediate for conduritol deravatives
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Gentisic acid reacted with methyl iodide in HMPA to give 94% of the corresponding methyl ester. Its oxidation with Ag2O in toluene afforded 57% of methoxycarbonylbenzoquinone as yellow crystals. Reaction of the latter with cyclopentadiene resulted in formation of methyl 3,6-dioxotricyclo[6.2.1.02,7]undeca-4,9-diene-2-carboxylate (21%).
- Mamaghani,Pourali
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Read Online
- The antioxidant properties of salicylate derivatives: A possible new mechanism of anti-inflammatory activity
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The synthesis and antioxidant evaluation by DPPH scavenging of a series of salicylic acid derivatives is described. Gentisic acid and its ester, amide, and amino analogs possess more radical scavenging capacity than salicylic acid and other salicylate derivatives. This property can possibly provide an additional pathway for anti-inflammatory activity through either single electron or hydrogen atom transfer, leading to a new strategy for the design of anti-inflammatory agents.
- Borges, Rosivaldo S.,Castle, Steven L.
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Read Online
- STEREOCONTROLLED SYNTHESIS OF CLERODIN HOMOLOG - A SYNTHETIC APPROACH TO STRUCTURE-ACTIVITY RELATIONSHIPS -
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In order to elucidate the structure-activity relationships of the antifeeding diterpenes having a neo-clerodane skeleton, clerodin homolog 5 was stereoselectively synthetized through 18 steps via a key intermediate 11.Perhydrofurofuran ring in the synthesized homolog was more unstable than that of the natural product, and gave a tri-MeOH adduct 3 in a similar behavior to that of the model compound 1 and 2.
- Kojima, Yasuhiro,Kato, Natsuki
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Read Online
- Macrocyclic pentamers functionalised around their periphery as potential building blocks
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The elaboration of a five-fold symmetric macrocyclic aromatic pentamer bearing peripheral benzyloxy and hydroxyl groups is described. These could be used to explore further functionalisation for use as pentagonal building blocks. The internal fluorine-substituted macrocycle has been prepared via a one-pot procedure which is an improvement on the stepwise chain growth approach reported in the literature.
- Nam, Seong,Ware, David C.,Brothers, Penelope J.
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Read Online
- Towards the development of a covalently tethered MALDI system - A study of allyl-modified MALDI matrixes
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An emerging application of matrix-assisted laser desorption ionization (MALDI) mass spectrometry is the analysis of low molecular weight (LMW) compounds, often via coupled, liquid chromatography - MALDI-MS methods. However, in many cases, the low molecular weight region of MALDI mass spectra is obscured by the presence of signals originating from the matrix, suggesting that the development of tethered MALDI matrixes may be required to optimize MS performance for such compounds. To gain insight into potential sites for covalent attachment of MALDI matrixes, we have systematically investigated the role played by a variety of functional group motifs in determining matrix efficiency for three common MALDI matrixes, as judged both by total signal intensity and background noise from matrix decomposition for a set of LMW compounds. A series of allyl derivatives of standard matrixes was prepared, and the efficiency of these materials in the MALDI experiment was measured. All modifications of established matrixes, e.g., 2,5-dihydroxybenzoic acid (DHB), α-cyano-4-hydroxycinnamic acid (CHCA), and caffeic acid (CA), or close analogues led to decreased absolute signal intensity and signal-to-background levels. Improved performance was generally observed with (i) the presence of a phenolic group (carboxylic acids were less effective) (ii) crystalline derivatives, and (iii) compounds that had high extinction coefficients at wavelengths near to that of the exciting laser (337 nm). The most interesting derivatives were the O-allyl ether (15) and N-allyl amide (16) of caffeic acid. These compounds did not facilitate signals from all four analytes tested. However, the observed spectra contained fewer signals from the matrix than from the parent compound CA. These compounds demonstrate that functionalization of MALDI matrixes, ultimately leading to tethered matrixes, is possible without jeopardizing signal intensity.
- Martic, Sanela,Brennan, John D.,Brook, Michael A.,Ackloo, Suzanne,Nagy, Noemi
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Read Online
- Studies on quinones. Part 35: Access to antiprotozoal active euryfurylquinones and hydroquinones
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(+)-Euryfuran adds regiospecifically to activated monosubstituted 1,4-benzoquinones under mild conditions to give the corresponding Michael adducts which, depending on the quinone substituent, undergo in situ redox reactions to the respective euryfurylbenzoquinones. One of these Michael adducts undergoes a facile stereoselective cyclisation under oxidant conditions to afford a naphthofuro[4,3-c]benzopyran derivative. The in vitro activities of the obtained euryfurylquinones and hydroquinones against Leishmania amazonensis are described.
- Valderrama, Jaime A.,Benites, Julio,Cortés, Manuel,Pessoa-Mahana, David,Prina, Eric,Fournet, Alain
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Read Online
- Bisketene Equivalents as Diels-Alder Dienes
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2,5-Bis(tert-butyldimethylsilyloxy)furans are established as vicinal bisketene equivalents for application as dienes in the Diels-Alder reaction. Cycloaddition with olefinic dienophiles, under exceptionally mild conditions, enables convergent access to highly substituted para-hydroquinones in unprotected form via a one-pot Diels-Alder/ring-opening/tautomerization sequence. The synthesis of para-benzoquinones from acetylenic dienophiles, including benzynes, is also demonstrated, and 2,5-bis(tert-butyldimethylsilyloxy)pyrroles are established as competent dienes for the synthesis of para-iminoquinones. Application in natural product synthesis enables gram-scale access to the neuroprotective agent (±)-indanostatin.
- Dissanayake, Isuru,Hart, Jacob D.,Becroft, Emma C.,Sumby, Christopher J.,Newton, Christopher G.
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supporting information
p. 13328 - 13333
(2020/09/03)
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- A Structure-Reactivity Relationship of the Tandem Asymmetric Dihydroxylation on a Biologically Relevant Diene: Influence of Remote Stereocenters on Diastereofacial Selectivity
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The Sharpless asymmetric dihydroxylation (AD) finds widespread use in natural product and drug molecule syntheses, in part, due to its efficiency and predictability. However, the tandem AD of dienes is much less studied, but important in complex molecular synthesis. Herein, a biologically relevant tandem AD is reported, and several anomalies are discovered with the accepted model. These include the formation of unpredicted diastereoisomers, with matched and mismatched stereocenters contradicting the Sharpless mnemonic device. From a structural analysis of the tandem AD, we present a strategy to improve asymmetric induction in sterically hindered alkenes using double diastereodifferentiation from a 9-bond distant stereocenter. A theoretical justification for the unpredicted stereoselectivity, accounting for the influence of steric hindrance and pre-installed chirality, is proposed.
- Gill, Daniel M.,Male, Louise,Jones, Alan M.
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supporting information
p. 7568 - 7577
(2019/12/11)
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- APOPTOSIS SIGNAL-REGULATING KINASE INHIBITORS AND USES THEREOF
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Described herein are ASK1 inhibitors and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for the treatment of blood disease, autoimmune disorders, pulmonary disorders, hypertension, inflammatory diseases, fibrotic diseases, diabetes, diabetic nephropathy, renal diseases, respiratory diseases, cardiovascular diseases, acute lung injuries, acute or chronic liver diseases, and neurodegenerative diseases.
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Paragraph 00281
(2019/04/09)
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- Mechanistic Studies of the Deslongchamps Annulation
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The Cs2CO3-mediated annulations ("Deslongchamps annulations") of three spirocyclic benzoquinone monoketals 5b-d with an ester or acyl substituent at C-2 to two tert-butyl esters of λδ-unsaturated β-ketocarboxyl acids ("Nazarov reagents" 2a,b) were monitored 1H NMR spectroscopically. This revealed that a primary product, by all likelihood the Michael adduct, forms fast and prior to the appearance of the Deslongchamps adduct. These primary products form reversibly. This was proved by two crossover and four scavenging experiments. Therein, components already incorporat.
- Kreibich, Michael,Petrovi?, Denis,Brückner, Reinhard
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supporting information
p. 1116 - 1133
(2018/02/14)
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- GLYCOMIMETICS FOR USE FOR THE TREATMENT OF VASCULAR CALCIFICATION AND/OR ENDOTHELIAL DYSFUNCTION
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The present invention relates to the use of glycomimetic compounds for the treatment of vascular calcification and/or endothelial dysfunction, particularly the use of small molecule mimetics of heparin/heparan sulfate, such as compounds according to formula (A), (B), (C) or (D), or pharmaceutically acceptable derivatives thereof
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Page/Page column 62
(2017/03/28)
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- Bisphthalonitrile monomer containing side chain substituted aromatic ester type mesogenic unit as well as preparation and application of bisphthalonitrile monomer
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The invention discloses a bisphthalonitrile monomer containing a side chain substituted aromatic ester type mesogenic unit as well as preparation and an application of the bisphthalonitrile monomer. A general formula of the bisphthalonitrile monomer containing the side chain substituted aromatic ester type mesogenic unit is represented in the specification, wherein M represents a side chain substituted aromatic group. Compared with the prior art, the bisphthalonitrile monomer has the advantages that through introduction of the mesogenic unit with a side chain, the melting temperature can be decreased, and the resin can be widely applied to a liquid crystal polymer material; according to the related monomer preparation method, the synthesis period is greatly shortened, raw materials for monomer synthesis are cheap and easily available, the preparation method is simple and convenient, and the yield is high.
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Paragraph 0040; 0043
(2017/01/23)
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- Mono-/dihydroxybenzoic acid esters and phenol pyridinium derivatives as inhibitors of the mammalian carbonic anhydrase isoforms I, II, VII, IX, XII and XIV
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Using hydroxy-/dihydroxybenzoic acids as leads, a series of methyl, ethyl and iso-propyl esters of 4-hydroxy-benzoic acid, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5-dihydroxybenzoic acids and of coumaric acid, were obtained and investigated for the inhibition of six mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that is, the cytosolic CA I, II and VII, and the transmembrane CA IX, XII and XIV, many of which are established drug targets. Other compounds incorporating phenol/catechol moieties were obtained from dopamine by reaction with fluorescein isothiocyanate or with 2,4,6-trisubstituted pyrylium salts. Some aminophenols were also derivatized in a similar manner, by using pyrylium salts. Many of these compounds showed increased inhibitory action compared to the lead compounds from which they were obtained, with efficacy in the submicromolar range against most investigated CA isoforms. As phenols are a class of less investigated CA inhibitors (CAIs) compared to the sulfonamides, and their mechanism of inhibition is less well understood, compounds of the type designed here may be helpful in gaining more insights into these phenomena.
- Carta, Fabrizio,Vullo, Daniela,Maresca, Alfonso,Scozzafava, Andrea,Supuran, Claudiu T.
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supporting information
p. 1564 - 1569
(2013/04/10)
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- Application of new photolabile protecting groups as photocleavable joints of block copolymers
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New photoresponsive block copolymers (BCPs) have been developed by incorporating photocleavable units. These photocleavable units are derived from robust photolabile protecting groups (PPGs); UV irradiation cleaves the BCPs and releases a well-defined chemically active functional group at the cleaved end of a PS polymer. The Royal Society of Chemistry 2013.
- Lu, Wenya,Tian, Chong,Thogaripally, Punith,Hu, Jun,Wang, Pengfei
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supporting information
p. 9636 - 9638
(2013/10/08)
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- Synthesis of novel benzoxazinone compounds as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
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(Chemical Equation Presented) Two benzoxazinone compounds as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors were synthesized and characterized by NMR and high-resolution mass spectrometry (HRMS). An efficient chlorination method was introduced in the synthesis of 4-chloro-2-oxo-2H- benzoxazinone-6-yl acetate. The inhibition activities of the target compounds and the important intermediates for EGFR tyrosine kinase activity in vitro were determined. Copyright Taylor & Francis Group, LLC.
- Chen, Shaopeng,Li, Xuemin,Wan, Shengbiao,Jiang, Tao
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scheme or table
p. 2937 - 2946
(2012/07/16)
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- Synthesis, structural investigations, hydrogen-deuterium exchange studies, and molecular modeling of conformationally stablilized aromatic oligoamides
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Biasing the conformational preferences of aromatic oligoamides by internally placing intramolecular hydrogen bonds has led to a series of stably folded molecular strands. This article presents the results from extensive solid-state, solution, and computational studies on these folding oligomers. Depending on its backbone length, an oligoamide adopts a crescent or helical conformation. Surprisingly, despite the highly repetitive nature of the backbone, the internally placed, otherwise very similar intramolecular hydrogen bonds showed significantly different stabilities as demonstrated by hydrogen-deuterium exchange data. It was also observed that the hydrogen-bonding strength can be tuned by adjusting the substituents attached to the exterior of the aromatic backbones. Examining the amide hydrogen-deuterium exchange rates of trimers revealed that a six-membered hydrogen bond nearing the ester end is the weakest among all the four intramolecular hydrogen bonds of a molecule. This observation was verified by ab initio quantum mechanical calculations at the level of B3LYP/6-31G. Such a "weak point" creates the "battle of the bulge" where backbone twisting is centered, which is consistently observed in the solid-state structures of the four trimer molecules studied. In the solid state, the oligomers assemble into interesting one-dimensional structures. A pronounced columnar packing of short oligomers (i.e., dimers, trimers, and tetramer) and channel-like, potentially ion-conducting stacks of longer oligomers (i.e., tetramer, pentamer, and hexamer) were observed.
- Yan, Yan,Qin, Bo,Ren, Changliang,Yip, Yeow Kwan,Ye, Ruijuan,Zeng, Huaqiang,Chen, Xiuying,Su, Haibin,Zhang, Dawei
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supporting information; experimental part
p. 5869 - 5879
(2010/07/13)
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- HISTONE LYSINE DEMETHYLASE INHIBITORS
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The invention provides a compound which is an iV-oxalylglycine derivative of formula (I): a hydroxamic acid derivative of formula (II): or a heteroaryl derivative of fomula (III): wherein n; Z1; Z2; Y1; Y2; A; p; X1; X2; m; R4; B; R5; R6; R7; R8; R9; X3; R10; R11 and R12 are as defined herein, or a pharmaceutically acceptable salt thereof. These compounds are inhibitors of the human 2-oxoglutarate-dependant JMJD2 subfamily of histone demethylases, in particular JMJD2E. Such inhibitors are useful in changing the epigenetic state of cells resulting in the inhibition / activation of chromatin remodelling, multiple gene activation / deactivation, and in treating cancer and other conditions characterised by undesirable cellular proliferation, and psychiatric disorders including depression.
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Page/Page column 69; 76
(2010/04/30)
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- Helical organization in foldable aromatic oligoamides by a continuous hydrogen-bonding network
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Introduction of a continuous internal hydrogen-bonding network suppressed the conformational flexibility of a series of oligoaromatic foldamers with a lengthened backbone. The helical ordering over up to six aromatic repeating units was established in solution by a 2D NOESY study and in the solid state by an X-ray diffraction method. Computational molecular modeling further corroborates the experimentally observed helical propagation in this class of foldable molecular strands.
- Yan, Yan,Qin, Bo,Shu, Yingying,Chen, Xiuying,Yip, Yeow Kwan,Zhang, Dawei,Su, Haibin,Zeng, Huaqiang
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supporting information; experimental part
p. 1201 - 1204
(2009/08/07)
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- Inhibitor scaffolds for 2-oxoglutarate-dependent histone lysine demethylases
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The dynamic methylation of histone lysyl residues plays an important role in biology by regulating transcription, maintaining genomic integrity, and by contributing to epigenetic effects. Here we describe a variety of inhibitor scaffolds that inhibit the human 2-oxoglutarate-dependent JMJD2 subfamily of histone demethylases. Combined with structural data, these chemical starting points will be useful to generate small-molecule probes to analyze the physiological roles of these enzymes in epigenetic signaling.
- Rose, Nathan R.,Ng, Stanley S.,Mecinovi?, Jasmin,Liénard, Beno?t M. R.,Bello, Simon H.,Sun, Zhe,McDonough, Michael A.,Oppermann, Udo,Schofield, Christopher J.
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supporting information; experimental part
p. 7053 - 7056
(2009/11/30)
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- Chemoselective esterification of phenolic acids in the presence of sodium bicarbonate in ionic liquids
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Chemoselective esterification of phenolic acids with dialkyl sulphates or alkyl halides in the presence of sodium bicarbonate in 1,3-dialkylimidazolium ionic liquids is reported in excellent yields and less reaction time as compared to organic solvents. Copyright Taylor & Francis Group, LLC.
- Ambika,Singh, Pradeep Pratap,Chauhan
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p. 928 - 936
(2008/09/17)
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- DBU-CH3I, a potential substitute for CH2N2 in the preparation of methyl esters and methyl aryl ethers: Studies with assorted acids
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DBU-CH3I has been poised to be a substitute for diazomethane in the preparation of methyl esters from carboxylic acids. The reactions can be carried out in commercial untreated acetone and acetonitrile, which have been exemplified with several methyl esters, otherwise it is difficult to prepare. Bis-esterification using diiodomethane can also be achieved in a similar fashion. Sufficiently acidic phenols are also conveniently O-methylated by the method. Copyright Taylor & Francis Group, LLC.
- Mal, Dipakranjan,Jana, Amit,Ray, Sutapa,Bhattacharya, Sourav,Patra, Asit,De, Saroj R.
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experimental part
p. 3937 - 3946
(2009/04/11)
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- Novel heparin/heparan sulfate mimics as inhibitors of HGF/SF-induced MET activation
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The synthesis of simple, non-sugar glycosaminoglycan (GAG) mimics has been achieved and the analogues evaluated for their ability to inhibit the activation of the MET receptor by hepatocyte growth factor/scatter factor (HGF/SF).
- Raiber, Eun-Ang,Wilkinson, James A.,Manetti, Fabrizio,Botta, Maurizio,Deakin, Jon,Gallagher, John,Lyon, Malcolm,Ducki, Sylvie W.
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p. 6321 - 6325
(2008/09/17)
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- NOVEL COMPOUNDS AS AGONIST FOR PPAR GAMMA AND PPAR ALPHA, METHOD FOR PREPARATION OF THE SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
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The present invention relates to novel compounds accelerating the activity of Peroxisome proliferator-activated receptor gamma (PPARγ) and alpha (PPARα), processes of preparing the same, and pharmaceutical compositions containing the same as an active agent.
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Page/Page column 154
(2010/11/27)
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- Compositions and methods for enhancing active agent absorption
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Compositions and methods for enhancing the absorption of active agents across the mucosa of animal subjects are provided. Methods of administration and appropriate dosage forms are also provided.
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Page/Page column 4
(2008/06/13)
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- A simple and effective method for chemoselective esterification of phenolic acids
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A new method for efficient and chemoselective esterification of phenolic acids in KHCO3/alkyl halide/DMF reaction system is described, by which a series of phenoic acid esters were obtained in excellent yields.
- Guo, Wei,Li, Junfei,Fan, Ningjuan,Wu, Weiwei,Zhou, Peiwen,Xia, Chizhong
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p. 145 - 152
(2007/10/03)
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- Hydroxy-methoxybenzoic methyl esters: Synthesis and antifeedant activity on the pine weevil, Hylobius abietis
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The pine weevil Hylobius abietis (L.) (Coleoptera: Curculionidae) feeds on the bark of coniferous seedlings and is the economically most important forestry restocking pest in large parts of Europe. Substances with an antifeedant effect may offer an environmentally friendly alternative to insecticides for the protection of planted seedlings. Bioassays were performed on commercial and synthetic methyl hydroxy-methoxybenzoates in order to determine their possible antifeedant activity. Two methyl hydroxy-methoxybenzoates were synthesized by esterification and mono-O-methylation of two dihydroxybenzoic acids. A regioselective protection-deprotection strategy was used in the synthetic pathway of the other non-commercial esters, esterification and selective pivaloylation of the less-hindered hydroxyl group of other commercial dihydroxybenzoic acids gave diester intermediates, which then were O-methylated before methanolysis of the pivaloyl group which yielded the desired non-commercial methyl hydroxy-methoxybenzoates. The five synthesized methyl hydroxy-methoxybenzoic esters were complemented with commercial samples of the five other isomers of methyl hydroxy-methoxybenzoate and spectrometric data were collected for the complete set of isomers. All ten isomers were tested for their antifeedant effect on the pine weevil. The effect varied considerably among the hydroxy-methoxybenzoic esters. Methyl 2-hydroxy-3-methoxybenzoate showed the highest effect and may thus be a candidate for practical use in pine weevil pest management.
- Legrand, Sacha,Nordlander, G?ran,Nordenhem, Henrik,Borg-Karlson, Anna-Karin,Unelius, C. Rikard
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p. 829 - 835
(2007/10/03)
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- First synthesis of (8-2H3)-(all-rac)-δ-tocopherol
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Trideuterated tocopherols were needed to be used as internal standards for our study about simultaneous quantitative determination of tocopherols in foodstuffs by mass spectrometry. Whilst procedures for trideuterated α-tocopherol have been recently optimized, no method is reported as regards δ-tocopherol. Different synthetic approaches are discussed, as well as the first procedure for the synthesis of (8-2H3)-(all-rac)-δ-tocopherol. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Mazzini, Francesco,Alpi, Emanuele,Salvadori, Piero,Netscher, Thomas
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p. 2840 - 2844
(2007/10/03)
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- Regiospecific Michael reaction of (+)-euryfuran with activated 1,4- benzoquinones
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(+)-Euryfuran cycloadds regiospecifically to activated monosubstituted 1,4-benzoquinones under mild conditions to give the corresponding Michael adducts which, depending on the quinone substituent, undergo in situ redox reactions to the respective euryfurylbenzoquinones. One of the reported Michael adducts undergoes a facile stereoselective cyclisation under oxidant conditions to afford a naphthofuro[4,3-c]benzopyran derivative. The regiospecificity of the Michael and cyclisation reactions are discussed. (C) 2000 Elsevier Science Ltd.
- Valderrama, Jaime A.,Cortés, Manuel,Pessoa-Mahana, David,Preite, Marcelo,Benites, Julio
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p. 3563 - 3566
(2007/10/03)
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- Experimental studies of Lewis acid catalyzed additions of long chained alcohols to activated 1,4-benzoquinone
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Lewis acid promoted additions of long chained alcohols to 2- carbomethoxy-1,4-benzoquinone (1) have been examined by using various LAs; AlCl3, TiCl4, MgBr2 and MgCl2. It has been found that the bidentate Lewis acid MgCl2, having ability to coordinate to both carbonyl oxygens (chelate control) of 2-carbomethoxy-1,4-benzoquinone (1), produced the addition product almost quantitatively at mild conditions. The MgCl2 catalyzed additions of alcohols have been utilized in the synthesis of rare 2- alkoxyhydroquinones (7a-e). The reactions between quinone 1, alcohol and AlCl3 or TiCl4 have also been investigated by using NMR spectroscopy.
- Hormi, Osmo E.O.,Moilanen, Anu M.
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p. 1943 - 1952
(2007/10/03)
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- Benzoxazinone and benzothiazinone derivatives having cardiovascular activity
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Compounds of formula I STR1 wherein R represents hydrogen, C1 -C6 alkyl, C5 -C7 cycloalkyl, methylene-dioxy or phenyl, which may be substituted by one or two groups independently selected from hydroxy, halogen, nitro, C1 -C6 alkyl or C1 -C6 alkoxy; R1 and R2 independently represent hydrogen, COOR3, --CONR4 R5, STR2 --OCONR4 R5, --OCOR3, --NR4 R5, --OCOOR6, --NR3 COR7, --NRCONR4 R5, --N=CH--NR4 R5, NO2, CN, OH, SR3, wherein R3 is hydrogen or C1 -C6 alkyl, R4 and R5 independently are hydrogen or C1 -C6 alkyl, R6 is C1 -C6 alkyl, and R7 is hydrogen, C1 -C6 alkyl or C1 -C6 alkoxy, with the proviso that R1 and R2 cannot be hydrogen at the same time; X is oxygen or sulphur; Y represents a C2 -C6 alkylene chain or a C5 -C7 cycloalkylene group; and their pharmaceutically acceptable salts are provided and their use in pharmaceutical compositions which may be used in the treatment of cardiovascular diseases.
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- Aromatic compounds containing basic and acidic termini useful as fibrinogen receptor antagonists
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This invention relates to novel compounds containing basic and acidic termini, pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of platelet aggregation, as thrombolytics, and/or for the treatment of thromboembolic disorders.
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- ALKYL AND ALKYLBENZYL ETHERS OF SUBSTITUTED HYDROQUINONES
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The present invention provides alkyl and alkylbenzyl ethers of substituted hydroquinones and pharmaceutical compositions containing them. The present invention further provides methods of using these compounds and compositions to inhibit monoamine oxidase, particularly monoamine oxidase B. The present invention further provides methods for the treatment of diseases involving monoamine oxidase
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- Benzoxazinone and benzothiazinone derivatives endowed with cardiovascular activity
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2,3-dihydro-4H-1,3-benzoxazin-4-ones and 2,3-dihydro-4H-1,3-benzothiaxin-4-ones of formula I wherein R represents hydrogen, (C1 6)alkyl, (C5 7)cycloalkyl, phenyl, phenyl substituted by hydroxy, halogen, nitro, (C1 6)alkyl, (C1 6)alkoxy, methylenedioxy; R1 and R2 independently represent hydrogen, amide, amino, carboxy, hydroxy, nitro, ciano, mercapto; X is an oxygen or sulphur atom; Y is a (C2 6)alkylene chain or (C2 6)cycloalkylene group; and the pharmaceutically acceptable acid or basic salts thereof.
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- Zatosetron, a Potent, Selective, and Long-Acting 5HT3 Receptor Antagonist: Synthesis and Structure-Activity Relationships
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Antagonists of 5HT3 receptors are clinically effective in treating nausea and emesis associated with certain oncolytic drugs, including cisplatin.Moreover, these agents may be useful in pharmacological management of several central nervous system disorders, including anxiety, schizophrenia, dementia, and substance abuse.Our studies on aroyltropanamides led to the discovery that dihydrobenzofuranyl esters and amides are potent 5HT3 receptor antagonists.Simple benzoyl derivatives of tropine and 3α-aminotropane possessed weak 5HT3 receptor antagonist activity, as judged by blockade of bradycardia produced by iv injection of serotonin (5HT) to anesthetized rats.Within this series, use of benzofuran-7-carboxamide as the aroyl moiety led to a substantial increase of 5HT3 receptor affinity.The optimal 5HT3 receptor antagonist identified via extensive SAR studies was endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(8-methyl-8-azabicyclooct-3-yl)-7-benzofurancarboxamide (Z)-2-butenedioate (zatosetron maleate).The 7-carbamyl regiochemistry, dimethyl substitution, chloro substituent, and endo stereochemistry were all crucial elements of the SAR.Zatosetron maleate was a potent antagonist of 5HT-induced bradycardia in rats (ED50=0.86 μg/kg iv).Low oral doses of zatosetron (30 μg/kg) produced long-lasting antagonism of 5HT3 receptors, as evidenced by blockade of 5HT-induced bradycardia for longer than 6 h in rats.Moreover, this compound did not produce hemodynamic effects after iv administration to rats, nor did it block carbamylcholine-induced bradycardia in doses that markedly blocked 5HT3 receptors.Thus, zatosetron is a potent, selective, orally effective 5HT3 receptor antagonist with a long duration of action in rats.
- Robertson, David W.,Lacefield, William B.,Bloomquist, William,Pfeifer, William,Simon, Richard L.,Cohen, Marlene L.
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p. 310 - 319
(2007/10/02)
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- A route for the enantioselective total synthesis of antheridic acid, the antheridium-inducing factor from anemia phyllitidis
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An effective route for the total synthesis of antheridic acid (1) has been devised in which the initial chiral intermediate 7 is generated by enantioselective catalytic reduction and transformed in a stereocontrolled fashion into key intermediates 9, 10, 13, and 2.
- Corey,Kigoshi, Hideo
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p. 5025 - 5028
(2007/10/02)
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- Pharmaceutical compounds
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Compounds are described of the following formula STR1 in which R1 and R2 are each hydrogen, C1-12 alkyl or C2-12 alkenyl, at least one of R1 and R2 being C1-12 alkyl or C2-12 alkenyl; X1 and X2 are each hydrogen or a protecting group; and Y is (a) --(CH=CH)n Z in which n is 1, 2 or 3 and Z is --CHO, --CH2 OH, --COR3, --(CH2)m --COR3 or --(CH2)p CH=CH(CH2)q --COR3 in which m is an integer of 1 to 12, p is an integer of 1 to 4, q is an integer of 1 to 10 and R3 is (i) --OH or (ii) --NR4 R5 where R4 and R5 are each hydrogen, C1-4 alkyl or optionally substituted phenyl, or R4 and R5 together with the nitrogen atom to which they are attached form a morpholino, pyrrolidinyl or piperidino ring, (b) --CH=NR6 in which R6 is (i) --OH, (ii) C1-12 alkyl optionally substituted by --OH, --COOH or --NR7 R8 where R7 and R8 are each hydrogen or C1-4 alkyl, (iii) optionally substituted phenyl or (iv) --NR9 R10 in which R9 is hydrogen and R10 is optionally substituted phenyl or C1-4 alkyl CO--, or in which R9 and R10 together with the nitrogen atom to which they are attached form a morpholino, pyrrolidinyl or piperidino ring, (c) --CH2 NHR11 in which R11 is C1-12 alkyl optionally substituted with hydroxy or carboxy or optionally substituted phenyl, or (d) --CHOHR12 or STR2 in which R12 is hydrogen or C1-12 alkyl; and lactones, salts and esters thereof; provided that when one of R1 and R2 is hydrogen and the other is C1-12 alkyl, Y is --(CH=CH)n Z, n is 1 and Z is --COOH only salts are included. The compounds have pharmaceutical activity.
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- A Selective Hydrolysis of Aryl Acetates
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Aryl and naphthyl acetates are efficiently hydrolyzed by reaction with toluene saturated with water and p-toluenesulfonic acid adsorbed on silica gel.The procedure allows the selective hydrolysis of aryl acetates in the presence of other ester groups.
- Blay, Gonzalo,Cardona, M. Luz,Garcia, M. Begona,Pedro, Jose R.
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p. 438 - 439
(2007/10/02)
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- Addition of (Methylthio)methyl p-Tolyl Sulfone to α,β-Unsaturated Carbonyl Compounds
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The lithio derivative of (methylthio)methyl p-tolyl sulfone (1) reacted with various α,β-unsaturated carbonyl compounds to afford adducts in good to high yields.The introduced (methylthio)(p-tolylsulfonyl)methyl group was easily converted to a (methylthio)carbonyl group or a formyl group.When the reaction of 1 with methyl acrylate using sodium hydride as a base was performed in DMF at an ambient temperature,2-(methoxycarbonyl)-4-(methylthio)-4-(p-tolylsulfonyl)cyclohexanone (8) was obtained in 81 percent yield.Furthermore, 8 was shown to be an important intermediate for preparing 2-substituted 2-(methoxycarbonyl)-1,4-cyclohexanediones.
- Ogura, Katsuyuki,Yahata, Nobuhiro,Minoguchi, Masanori,Ohtsuki, Kazuo,Takahashi, Kazumasa,Iida, Hirotada
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p. 508 - 512
(2007/10/02)
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- 9,10-syn-PODOCARPANE DITERPENOIDS. VI. DIELS-ALDER CYCLOADDITION OF (ACETOXYVINYL)CYCLOHEXENES TO QUINONES
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The outcome of the cycloaddition reactions of 3-methoxycarbonyl-1,2-benzoquinone with 1-(1-acetoxyvinyl)cyclohexene and of 4-methoxycarbonyl-1,2-benzoquinone and 2-methoxycarbonyl-1,4-benzoquinone with 1-(1-acetoxyvinyl)- and 1-(2-acetoxyvinyl)-cyclohexene is described.
- Forte, Maurizio,Orsini, Fulvia,Pelizzoni, Francesca,Ricca, Giuliana
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- Synthesis of Substituted Phenazines from Benzofurazanoxid and Hydroquinones
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The sterical course of the formation of substituted phenazines from benzofurazanoxid and hydroquinone derivatives was investigated.The additional functional group of the hydroquinone determines the substitution pattern and the product ratio of the phenazines formed. - Key words: Phenazine, Synthese, Hydrochinone
- Roemer, A.,Sammet, M.
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p. 866 - 872
(2007/10/02)
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- Synthesis of hydroxy- and amino-substituted benzohydroxamic acids: Inhibition of ribonucleotide reductase and antitumor activity
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Benzohydroxamic acids inhibit mammalian ribonucleotide reductase and exhibit antineoplastic activity in L1210 leukemic mice. Five new hydroxy- and amino-substituted benzohydroxamic acids (3,4- and 3,5-OH,3,4-NH2, 2,3,4-, and 3,4,5-OH) were prepared and tested along with 12 previously reported benzohydroxamic acids (BHA) for enzyme inhibition and antitumor activity. The most potent enzyme inhibitor in this series was 2,3,4-OH-BHA (ID50=3.5 μM), which is 140 times more potent than hydroxyurea, but its toxicity limited the antitumor activity to a 30% increase in life span of L1210 bearing mice at 125 (mg/kg) day ip for 8 days. The most effective antitumor agent in this series was 3,4-OH-BHA which prolonged the life span of L1210 bearing mice 103% at 600 (mg/kg)/day ip for 8 days.
- van't Riet,Wampler,Elford
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p. 589 - 592
(2007/10/05)
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