- CuLi2Cl4 catalysed cross-coupling strategy for the formal synthesis of the diterpenoid (+)-subersic acid from (?)-sclareol
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A CuLi2Cl4-catalysed regioselective cross-coupling is used in a key step leading to the concise synthesis of (+)-subersic acid with an overall yield of 25.7% from commercially available (-)-sclareol. The coupled product 15-(2-methoxy-5-carbomethoxy)phenyl-labda-8(9),13Ediene was obtained in 62% yield under CuLi2Cl4 conditions starting from 2-iodo-4-carbomethoxyanisole and 15-acetoxy-labda-8(9),13Ediene. These were derived from 4-hydroxybenzoic acid and (-)-sclareol respectively. The 15-(2-methoxy-5-carbomethoxy)phenyl-labda- 8(9),13E-diene was easily transformed into (+)-subersic acid by demethylation of the phenol ether and ester. This cross-coupling strategy showed a good functional group tolerance and various (+)-subersic acid derivatives were obtained in moderate yields.
- Wu, Qiangyong,Wang, Peiqiang,Zhou, Bin,Hua, Sikai,Ren, Jiangmeng,Zeng, Bu-Bing
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Read Online
- Palladium-Catalyzed Chemoselective Oxidative Addition of Allyloxy-Tethered Aryl Iodides: Synthesis of Medium-Sized Rings and Mechanistic Studies
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This Letter describes a Pd-catalyzed Tsuji-Trost-type/Heck reaction with allyloxy-tethered aryl iodides and aziridines. The strategy provides efficient access to benzannulated medium-sized rings via intermolecular cyclization. The substrate aryl iodide ha
- Liu, Ce,Li, Yuke,Shi, Wei-Yu,Ding, Ya-Nan,Zheng, Nian,Liu, Hong-Chao,Liang, Yong-Min
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supporting information
p. 4311 - 4316
(2021/05/26)
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- Biomimetic carbene cascades enabled imine derivative migration from carbene -bearing thiocarbamates
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Inspired by the body circulation of Omeprazole (irreversible proton pump inhibitor), we disclose the carbene-triggered cascades for the synthesis of 2-aminobenzofuran derivatives from N-sulfonyl-1,2,3-triazoles or benzothioazole-bearing thiocarbamates, which represents an unprecedented imine derivative migration process. Furthermore, the desulfurizing reagent-free Barton-Kellogg-type reactions starting from N-sulfonyl-1,2,3-triazoles have also been achieved for the first time, and elemental sulfur is confirmed as a byproduct during this transformation. Both experimental data and DFT calculations further thoroughly explained the unique reactivity.
- Li, Xue,Chen, Haohua,Xuan, Qingqing,Mai, Shaoyu,Lan, Yu,Song, Qiuling
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supporting information
p. 3518 - 3523
(2021/05/29)
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- Efficient and sustainable laccase-catalyzed iodination of: P -substituted phenols using KI as iodine source and aerial O2 as oxidant
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The laccase-catalyzed iodination of p-hydroxyarylcarbonyl- and p-hydroxyarylcarboxylic acid derivatives using KI as iodine source and aerial oxygen as the oxidant delivers the corresponding iodophenols in a highly efficient and sustainable manner with yields up to 93% on a preparative scale under mild reaction conditions.
- Sdahl, Mark,Conrad, Jürgen,Braunberger, Christina,Beifuss, Uwe
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p. 19549 - 19559
(2019/07/05)
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- Imidazole-containing condensed tricyclic compound and application thereof
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The invention discloses an imidazole-containing condensed tricyclic compound adopting the structure as shown in the formula (I) or pharmaceutically acceptable salts, stereisomers or prodrug molecules thereof. The imidazole-containing condensed tricyclic compound has the IDO1 activity regulation function, can enhance T-cell activation through blocking immune checkpoints IDO1, is used for treating IDO1-mediated immunosuppression, and therefore, can become an effective medicine for treating malignant tumors. When used together with checkpoint protein anti-body drugs or other anti-cancer drugs, the imidazole-containing condensed tricyclic compound can enhance the anti-cancer effect. Meanwhile, the imidazole-containing condensed tricyclic compound has the potential of effectively treating IDO1 abnormity related immunosuppressive diseases and has a high application value.
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- N-Iodosuccinimide (NIS) in Direct Aromatic Iodination
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N-Iodosuccinimide (NIS) in pure trifluoroacetic acid (TFA) offers a time-efficient and general method for the iodination of a wide range of mono- and disubstituted benzenes at room temperature, as demonstrated in this paper. The starting materials were generally converted into mono-iodinated products in less than 16 hours at room temperature, without byproducts. A few deactivated substrates needed addition of sulfuric acid to increase the reaction rate. Another exception was methoxybenzenes that preferentially were iodinated by NIS in acetonitrile with only catalytic amounts of TFA.
- Bergstr?m, Maria,Suresh, Ganji,Naidu, Veluru Ramesh,Unelius, C. Rikard
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p. 3234 - 3239
(2017/06/21)
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- OXADIAZOLE MODULATORS OF S1P METHODS OF MAKING AND USING
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The invention is directed to Compounds of Formula (I): wherein each variable is defined herein, as well as methods of making and using the compounds as agonists of S1P1 and/or S1P5 for instance for treating graft versus host disease and autoimmune diseases.
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Paragraph 0156
(2017/01/23)
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- One-pot syntheses of 2,6-diiododiaryl ethers from para-EWG-substituted phenols by diacetoxyiodobenzene
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2,6-Diiododiaryl ethers are not only useful blocks to construct substituted diaryl ethers but are also characteristic drug precursors. In this research, a one-pot tandem oxidation of phenols substituted with electron-withdrawing group at the para position by excess diacetoxyiodobenzene is proven as a novel and efficient method for preparing 2,6-diiododiaryl ethers. Using this method, three new 2,6-diiododiaryl ethers, namely, methyl 3,5-diiodo-2-methoxy-4-phenoxybenzoate (2), methyl 3,5-diiodo-4-phenoxybenzoate (6), and 1-(2,6-diiodo-4-nitrophenoxy)benzene (7) were readily obtained from the corresponding phenols, and the yields were good.
- Zhou, De-Jun,Yin, Shu-Qiang,Fan, Yun-Chang,Wang, Qiang
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p. 5387 - 5394
(2016/06/01)
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- Heterocyclic modulators of cannabinoid receptors
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Heterocyclic compounds which modulate cannabinoid receptors are presented. Pharmaceutical compositions containing these compounds, methods of using these compounds as modulators of cannabinoid receptors and processes for synthesizing these compounds are a
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- NEUROPROTECTIVE CB2 RECEPTOR AGONISTS
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A method of treating or preventing a neuroinflammatory and/or neurodegenerative disease in a subject by administering a pharmaceutically effective amount of a CB2 receptor agonist is described. The CB2 receptor agonist can be a compo
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- ORGANIC COMPOUNDS
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Novel benzofuran derivatives are disclosed. The derivatives have S1P1 receptor activity and/or disease modifying activity and find use in the treatment of conditions or diseases associated with the immune, vascular and nervous systems in animals and/or humans
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Page/Page column 74
(2014/05/24)
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- OXADIAZOLE SUBSTITUTED INDAZOLE DERIVATIVES FOR USE AS SPHINGOSINE 1-PHOSPHATE 1 (S1P1) RECEPTOR AGONISTS
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Oxadiazole substituted indazole derivatives of formula (I) or pharmaceutical salts thereof having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their uses in the treatment of various disorders mediated by S1P1 receptors are disclosed.
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Page/Page column 16-17
(2012/11/13)
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- Environmental friendly method for the iodination of moderately active arenes
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An effective and environmental friendly method for the iodination of various moderately active methoxy arenes, phenols and anilines using hydrogen peroxide and acidified sodium periodate in aqueous ethanol medium is reported. The extent of iodination is e
- Sathiyapriya
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experimental part
p. 41 - 43
(2011/11/13)
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- OXADIAZOLE SUBSTITUTED INDAZOLE DERIVATIVES FOR USE AS SPHINGOSINE 1-PHOSPHATE 1 (S1P1) RECEPTOR AGONISTS
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Oxadiazole substituted indazole derivatives of formula (I) or pharmaceutical salts thereof having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their uses in the treatment of various disorders mediated by S1P1 receptor are disclosed.
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Page/Page column 16; 23-24
(2011/07/07)
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- Modulators of S1P and Methods of Making And Using
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The invention is directed to Compounds of Formula I: as well as methods of making and using the compounds.
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Page/Page column 60
(2010/10/19)
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- Domino ring-opening/carboxamidation reactions of N-tosyl aziridines and 2-halophenols/pyridinol: Efficient synthesis of 1,4-benzo- And pyrido-oxazepinones
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"Chemical Equation Presented" A domino process is described for the synthesis of 1,4-benzo- and pyrido-oxazepinones by one-pot sequential ring-opening/carboxamidation reactions of various N-tosylaziridines with a range of 2-halophenols/pyridinol under phase-transfer catalysis.
- Chouhan, Gagan,Alper, Howard
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supporting information; experimental part
p. 192 - 195
(2010/04/02)
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- Synthesis of dihydrobenzofurans via palladium-catalyzed annulation of 1,3-dienes by o -iodoaryl acetates
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The palladium-catalyzed annulation of 1,3-dienes by o-iodoaryl acetates provides an efficient approach to biologically interesting dihydrobenzofurans. The annulation is believed to proceed via (1) oxidative addition of the aryl iodide to Pd(0), (2) syn-ad
- Rozhkov, Roman V.,Larock, Richard C.
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supporting information; experimental part
p. 4131 - 4134
(2010/09/05)
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- Terphenly derivatives, preparation thereof, compositions containing same
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The invention relates to terphenyl derivatives of formula: and to their preparation and to the pharmaceutical compositions comprising them. These compounds exhibit an antagonist activity with respect to CB1 cannabinoid receptors.
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Page/Page column 4-5
(2008/06/13)
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- An effective method for the synthesis of 13C-labeled polyprenylhydroxybenzoic acids
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The synthesis of side-chain 13C-labeled geranylgeranyl-4- hydroxybenzoic acids and geranylgeranyl-3,4-dihydroxybenzoic acids is described. The synthesis starts from O-protected methyl hydroxyiodobenzoates, which are transformed into Grignard re
- Lang, Martin,Steglich, Wolfgang
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p. 1019 - 1027
(2007/10/03)
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- CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS
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Compounds useful for treating cellular proliferative diseases and disorders by modulating the activity of one or more mitotic kinesins are disclosed.
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Page/Page column 253-254
(2008/06/13)
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- NOVEL MCH RECEPTOR ANTAGONISTS
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The present invention relates to a melanin concentrating hormone antagonist compound of formula I: or a pharmaceutically acceptable salt thereof, useful for the treamtment useful fog treating Type H diabetes and/or obesity.
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Page/Page column 59-60
(2010/02/11)
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- COMPOUNDS HAVING BOTH α7 NICOTINIC AGONIST ACTIVITY AND 5HT3 ANTAGONIST ACTIVITY FOR TREATMENT OF CNS DISEASES
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The invention discloses compounds that are selective α7 nAChR agonists and 5-HT3 antagonists. The compounds are useful for treating many CNS diseases.
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Page 54 - 55
(2010/02/06)
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- Substituted 7-aza[2.2.1]bicycloheptanes for the treatment of disease
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The invention provides compounds of Formula I: which may be in the form of pharmaceutical acceptable salts or compositions, are useful in treating diseases or conditions in which α7 nicotinic acetylcholine receptors (nAChRs) are known to be involved.
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- Azabicyclic compounds for the treatment of disease
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The invention provides compounds of Formula I: 1wherein Azabicyclo is 2These compounds may be in the form of pharmaceutical salts or compositions, may be in pure enantiomeric form or racemic mixtures, and are useful in pharmaceuticals in which α7 is known to be involved.
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- New enzymes and prodrugs for ADEPT
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The present invention relates to nucleic acid molecules encoding mutant human carboxypeptidase A enzymes, and encoding conjugates of targeting molecules and mutant human carboxypeptidase A enzymes. The invention further relates to vectors and cell lines containing such nucleic acid molecules.
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- Optimization of alkylidene hydrazide based human glucagon receptor antagonists. Discovery of the highly potent and orally available 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6-tetramethylbenzyl)-1h-indol-4ylmethylene]hydrazide
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Highly potent human glucagon receptor (hGluR) antagonists have been prepared employing both medicinal chemistry and targeted libraries based on modification of the core (proximal) dimethoxyphenyl group, the benzyl ether linkage, as well as the (distal) benzylic aryl group of the lead 2, 3-cyano-4-hydroxybenzoic acid (3,5-dimethoxy-4-isopropylbenzyloxybenzylidene)hydrazide. Electron-rich proximal aryl moieties such as mono- and dimethoxy benzenes, naphthalenes, and indoles were found to be active. The SAR was found to be quite insensitive regarding the linkage to the distal aryl group, since long and short as well as polar and apolar linkers gave highly potent compounds. The presence of a distal aryl group was not crucial for obtaining high binding affinity to the hGluR. In many cases, however, the affinity could be further optimized with substituted distal aryl groups. Representative compounds have been tested for in vitro metabolism, and structure - metabolism relationships are described. These efforts lead to the discovery of 74, NNC 25-2504, 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6tetramethylbenzyl)-1H-indol-4-ylmethylene]hydrazide, with low in vitro metabolic turnover. 74 was a highly potent noncompetitive antagonist of the human glucagon receptor (IC50 = 2.3 nM, KB = 760 pM) and of the isolated rat receptor (IC50 = 430 pM, KB = 380 pM). Glucagonstimulated glucose production from isolated primary rat hepatocytes was inhibited competitively by 74 (Ki = 14 nM). This compound was orally available in dogs (Fpo = 15%) and was active in a glucagon-challenged rat model of hyperglucagonemia and hyperglycemia.
- Madsen, Peter,Ling, Anthony,Plewe, Michael,Sams, Christian K.,Knudsen, Lotte B.,Sidelmann, Ulla G.,Ynddal, Lars,Brand, Christian L.,Andersen, Birgitte,Murphy, Douglas,Teng, Min,Truesdale, Larry,Kiel, Dan,May, John,Kuki, Atsuo,Shi, Shenghua,Johnson, Michael D.,Teston, Kimberly Ann,Feng, Jun,Lakis, James,Anderes, Kenna,Gregor, Vlad,Lau, Jesper
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p. 5755 - 5775
(2007/10/03)
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- Human glucagon receptor antagonists based on alkylidene hydrazides.
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A series of alkylidene hydrazide derivatives containing an alkoxyaryl moiety was optimized. The resulting hydrazide-ethers were competitive antagonists at the human glucagon receptor. Pharmacokinetic experiments showed fast clearance of most of the compou
- Ling, Anthony,Plewe, Michael,Gonzalez, Javier,Madsen, Peter,Sams, Christian K,Lau, Jesper,Gregor, Vlad,Murphy, Doug,Teston, Kimberly,Kuki, Atsuo,Shi, Shenghua,Truesdale, Larry,Kiel, Dan,May, John,Lakis, James,Anderes, Kenna,Iatsimirskaia, Eugenia,Sidelmann, Ulla G,Knudsen, Lotte B,Brand, Christian L,Polinsky, Alex
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p. 663 - 666
(2007/10/03)
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- Iodothyronine Deiodinase Mimics. Deiodination of o,o'-Diiodophenols by Selenium and Tellurium Reagents
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To better understand, and in the extension mimic, the action of the three selenium-containing iodothyronine deiodinases, o,o'-diiodophenols were reacted under acidic conditions with sodium hydrogen telluride, benzenetellurol, sodium hydrogen selenide, or benzeneselenol and under basic conditions with the corresponding deprotonated reagents. Sodium hydrogen telluride was found to selectively remove one iodine from a variety of 4-substituted o,o'-diiodophenols, including a protected form of thyroxine (T4). Thus, it mimics the D1 variety of the iodothyronine deiodinases. Sodium telluride was a more reactive deiodinating agent toward o,o'-diiodophenols, often causing removal of both halogens. Benzenetellurol and sodium benzenetellurolate sometimes showed useful selectivity for monodeiodination. However, the products were often contaminated by small amounts of organotellurium compounds. Sodium hydrogen selenide, sodium selenide, benzeneselenol, and sodium benzeneselenolate were essentially unreactive toward o,o'-diiodophenols. To gain more insight into thyroxine inner-ring deiodination, substituted 2,6-diiodophenyl methyl ethers were treated with some of the chalcogen reagents. Reactivity and selectivity for monodeiodination varied considerably depending on the substituents attached to the aromatic nucleus. In general, it was possible to find reagents that could bring about the selective mono- or dideiodination of these substrates.
- Vasil'ev, Andrei A.,Engman, Lars
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p. 3911 - 3917
(2007/10/03)
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- SmI2-mediated sequential radical cyclization/anionic capture of aryl iodides on solid support
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Aryl radicals were generated by SmI2 on solid support, cyclized on to C=C bond, and reduced to their organosamarium anionic species followed by electrophilic capture. However, the capture reaction was substrate-dependant in solution and on soli
- Du, Xiaohui,Armstrong, Robert W.
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p. 2281 - 2284
(2007/10/03)
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- A Facile Route to 3a,8a-Dihydrofurobenzofurans.
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Consecutive employment of palladium-catalysis and samarium(II)iodide-induced radical chemistry allows access to analogues of the ABC enol ether tricycle of aflatoxin B1 (1).The Pd-assisted coupling of tributylstannyl ethers of various 2-iodophenols with 2
- Holzapfel, Cedric W.,Williams, D. Bradley G.
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p. 8555 - 8564
(2007/10/02)
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