- Asymmetric synthesis of (S)-(-)-acromelobinic acid
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A total synthesis of (S)-(-)-acromelobinic acid 2, which was isolated from clitocybe acromelalga, was achieved via an asymmetric hydrogenation protocol. Dehydroamino acid derivative 12 was prepared from 2,5-lutidine 5 and subjected to asymmetric hydrogenation using (S,S)-[Rh(Et-DuPHOS)(COD)]BF4 to give the (S)-(+)-pyridylalanine derivative 13 in 93% yield and >96% e.e. Removal of the protecting groups in (S)-(+)-13 afforded (S)-(-)-acromelobinic acid 2.
- Adamczyk, Maciej,Akireddy, Srinivasa Rao,Reddy, Rajarathnam E.
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Read Online
- Synthesis of Esters by Functionalisation of CO2
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The invention relates to a method for (I) producing a carboxylic ester of formula (I). Said method comprises the steps of: a) bringing an organosilane/borane of formula Si or B into contact with CO2, in the presence of a catalyst and an electrophilic compound of formula (III), the groups R1, R2, R3, R4, R5, Y, and M′ being as defined in claim 1; and optionally b) recovering the compound of formula (I) produced.
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Paragraph 0129
(2017/09/06)
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- SUBSTITUTED BENZOXAZOLES
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The invention relates to substituted benzoxazoles and to processes for their preparation and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular of cardiovascular disorders, preferably of thrombotic or thromboembolic disorders.
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Paragraph 1604-1605
(2016/05/10)
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- Substituted benzoxazoles
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The invention relates to substituted benzoxazoles of formula (1) where R1 stands for a group of formula, and a method for preparing same and their use in the production of drugs for the treatment and/or prevention of diseases, in particular cardiovascular diseases, preferably thrombotic or thromboembolic diseases.
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Paragraph 0509
(2016/10/10)
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- CO2 Conversion into Esters by Fluoride-Mediated Carboxylation of Organosilanes and Halide Derivatives
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A one-step conversion of CO2 into heteroaromatic esters is presented under metal-free conditions. Using fluoride anions as promoters for the C-Si bond activation, pyridyl, furanyl, and thienyl organosilanes are successfully carboxylated with CO2 in the presence of an electrophile. The mechanism of this unprecedented reaction has been elucidated based on experimental and computational results, which show a unique catalytic influence of CO2 in the C-Si bond activation of pyridylsilanes. The methodology is applied to 18 different esters, and it has enabled the incorporation of CO2 into a polyester material for the first time. Metal free! A novel methodology is described to convert CO2 into heteroaromatic esters in the presence of organosilanes and organic halides using fluoride anions as promoters for the C-Si bond activation (see scheme). CO2 exhibits a unique catalytic influence in the C-Si bond cleavage of pyridylsilanes, serving as a traceless activator.
- Frogneux, Xavier,Von Wolff, Niklas,Thuéry, Pierre,Lefèvre, Guillaume,Cantat, Thibault
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p. 2930 - 2934
(2016/03/25)
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- Development of an iron(II)-catalyzed aerobic catechol cleavage and biomimetic synthesis of betanidin
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An aerobic iron(II)-catalyzed cleavage of catechols was developed. This reaction allows for the preparation of 2-methoxy-2H-pyrans that can be employed as versatile building blocks for synthesis. The utility of this biomimetic oxidative cleavage is featured in the synthesis of betanidin, a natural colorant with antioxidant properties. Cut and paste: An aerobic iron(II)-catalyzed oxidative cleavage of catechol was developed. This reaction allows the preparation of 2H-pyrans that can be employed as versatile building blocks for synthesis. The utility of this biomimetic cleavage is featured in the synthesis of betanidin, the aglycone of red beets' principal colorant and itself a valuable antioxidant (see scheme).
- Guimond, Nicolas,Mayer, Peter,Trauner, Dirk
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supporting information
p. 9519 - 9523
(2014/08/18)
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- NEW COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
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This invention provides novel compounds and the novel compounds for use as a medicine, more in particular for the prevention or treatment of neurodegenerative disorders, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, and disorders characterised by cytotoxic α-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such neurodegenerative disorders. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds. The compounds have the formula (A1) wherein R1, R2, R4, R6, E, n, Y1, Y2, Y3, Y4, Y5, L, B, R8, and m are as defined in the claims.
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Paragraph 0620-0621
(2013/10/22)
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- NOVEL COMPOUNDS
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This invention relates to compounds of formula (I) their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, Ar, R1, R2, R3 have meanings given in the description.
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Page/Page column 47
(2013/06/27)
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- NOVEL COMPOUNDS
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This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, Ar, R1, R2, R3 have meanings given in the description.
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Paragraph 0242
(2013/06/05)
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- AMIDO-PYRIDYL ETHER COMPOUNDS AND COMPOSITIONS AND THEIR USE AGAINST PARASITES
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The subject matter disclosed herein is directed to amido-pyridyl ether compounds of formula I: wherein, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, Ra, a, b and d are as described herein, compositions comprising the compounds of formula I, methods for their preparation and methods for their uses against parasites.
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Page/Page column 57
(2013/03/26)
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- NEW COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
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This invention provides novel compounds and the novel compounds for use as a medicine, more in particular for the prevention or treatment of neurodegenerative disorders, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, and disorders characterised by cytotoxic α-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such neurodegenerative disorders. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds. The compounds have the formula (A1) wherein R1, R2, R4, R6, E, n, Y1, Y2, Y3, Y4, Y5, L, B, R8, and m are as defined in the claims.
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Page/Page column 83-84
(2012/06/30)
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- CARBAMOYL COMPOUNDS AS DGAT1 INHIBITORS 190
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DGAT-1 inhibitor compounds of formula (I), pharmaceutically-acceptable salts and pro- drugs thereof are described, together with pharmaceutical compositions, processes for making them and their use in treating, for example, obesity wherein, for example, Ring A is optionally substituted 2,6-pyrazindiyl; X is =O; Ring B is optionally substituted 1,4-phenylene; Y1 is a direct bond or -O-; Y2 is -(CH 2) r- wherein r is 2 or 3; n is 0 or n is 1 when Y1 is a direct bond between Ring B and Ring C and when Ring B is 1,4-phenylene and Ring C is (4-6C)cycloalkane; Ring C is optionally substituted (4-6C)cycloalkane, (7-10C)bicycloalkane, (8-12C)tricycloalkane, phenylene or pryidindiyl; L is a direct bond or -O-; p is 0, 1 or 2 and when p is 1 or 2 RA1 and RA2 are each independently hydrogen or (1-4C)alkyl; Z is carboxy or a mimic or bioisostere thereof.
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Page/Page column 84
(2009/07/25)
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- 2,4-DIAMINO-PYRIMIDINE DERIVATIVES
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The invention concerns compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, Q, R3, and R4 are as defined in the description. The present invention also relates to processes for the preparation ofsuch compounds, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours or other proliferative conditions which are sensitive to the inhibition of EphB4 kinases.
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Page/Page column 61-62
(2009/03/07)
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- ANDROGEN RECEPTOR ANTAGONISTS
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The present invention provides an androgen receptor antagonistic agent and a superior prophylactic or therapeutic agent for hormone-sensitive cancer, which contain a compound of the formula: wherein, R1 is a hydrogen atom, a group binding through a carbon atom, a group binding through a nitrogen atom, a group binding through an oxygen atom or a group binding through a sulfur atom; R2 is a hydrogen atom, a group binding through a carbon atom, a group binding through a nitrogen atom, a group binding through an oxygen atom or a group binding through a sulfur atom, R3 is a hydrogen atom, a hydrocarbon group which may have substituent (s) , an acyl group or a heterocyclic group which may have substituent(s), R4 is a hydrogen atom, a group binding through a carbon atom, a group binding through a nitrogen atom, a group binding through an oxygen atom or a group binding through a sulfur atom, and R5 is a cyclic group which may have substituent(s); or a salt thereof, or its prodrug.
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- Nonproteinogenic amino acids: An efficient asymmetric synthesis of (S)-(-)-acromelobic acid and (S)-(-)-acromelobinic acid
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An efficient synthesis of (S)-(-)-acromelobic acid (1) and (S)-(-)-acromelobinic acid (2) is described via asymmetric hydrogenation protocol. Asymmetric hydrogenation of dehydroamino acid derivative 23 using (R,R)-[Rh(DIPAMP)(COD)]BF4 catalyst followed by removal of the protective groups afforded (S)-(-)-acromelobic acid (1) in >98% ee. The key intermediate 23 was prepared from citrazinic acid (8). The dehydroamino acid derivative 33 required for the synthesis of (S)-(-)-2 was prepared from 2,5-lutidine (27), which upon hydrogenation using (S,S)-[Rh(Et-DuPHOS)(COD)]BF4 catalyst afforded (S)-(+)-34 in 93% yield and >96% ee. Removal of protective groups in (S)-(+)-34 afforded (S)-(-)-acromelobinic acid (2) in good overall yield.
- Adamczyk, Maciej,Akireddy, Srinivasa Rao,Reddy, Rajarathnam E
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p. 6951 - 6963
(2007/10/03)
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- Synthesis of substituted pyridines via regiocontrolled [4 + 2] cycloadditions of oximinosulfonates
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Diels-Alder cycloadditions of oximinosulfonate 8 with a variety of 1, 3-dienes proceed with regiochemistry opposite to that observed with conventional imino dienophiles, providing expeditious synthetic routes to substituted pyridines, tetrahydropyridines, and pyrrolines. The oximinosulfonate 8 is prepared in one convenient synthetic operation from Meldrum's acid and reacts with conjugated dienes at -78 C in the presence of 2 equiv of dimethylaluminum chloride to afford [4 + 2] cycloadducts in good to excellent yield. Exposure of these cycloadducts to the action of NaOMe and JV-chlorosuccinimide in methanol-THF at room temperature then produces substituted pyridines. The utility of this new two-step annulation protocol is demonstrated in total syntheses of the pyridine alkaloids fusaric acid and (S)-(+)-fusarinolic acid. Heating the [4 + 2] cycloadducts derived from 8 in a mixture of acetonitrile and pH 7 phosphate buffer induces an unusual Stieglitztype rearrangement leading to the formation of interesting spirobicyclic pyrrolines.
- Renslo, Adam R.,Danheiser, Rick L.
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p. 7840 - 7850
(2007/10/03)
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- Catechol 2,3-Dioxygenase-catalyzed Synthesis of Picolinic Acids from Catechols
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Various picolinic acid derivatives were synthesized from ammonia and hydroxymuconic semialdehyde derivatives that were oxidatively prepared from various catechols by the action of Pseudomonas catechol 2,3-dioxygenase (C23O, metapyrocatechase).
- Asano, Yasuhisa,Yamamoto, Yasushi,Yamada, Hideaki
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p. 2054 - 2056
(2007/10/02)
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- MULTIPLE PATHS FOR PHOTOALKYLATION OF PYRIDINECARBOXYLIC ESTERS IN ALCOHOLS
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Photochemical substitution of ring hydrogen of pyridinecarboxylic esters by alkyl groups derived from solvent alcohols occurs in several paths: 1) alkylation initiated by excited carbonyl moiety of the ester group and 2) alkylation initiated by the excitation of the ?-electronic system of the pyridine ring.In the photoreaction of methyl 3-pyridinecarboxylate in acidic methanol, three types of excited state (two triplet states for alkylation and a singlet state for alkoxylation) contribute simultaneously.
- Sugiyama, Toru,Tobita, Estuo,Takagi, Kyoko,Sato, Michitsugu,Kumagai, Yasuyuki,et al.
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p. 131 - 134
(2007/10/02)
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