- Asymmetric Aminations and Kinetic Resolution of Acyclic α-Branched Ynones
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An efficient method for asymmetric synthesis of acyclic α-tertiary amine derivatives has been achieved through enantioselective aminations of α-branched ynones with azodicarboxylates enabled by chiral phosphoric acid catalysis. Moreover, kinetic resolution of racemic starting material was realized under these conditions, which gave access to valuable enantioenriched α-substituted ketones. A wide array of α-aryl and alkyl-substitutions, and the substituted alkynyl groups were well compatible with this method, producing both the amination products and the recovered ketones with good to high enantioselectivities.
- He, Faqian,Shen, Guosong,Yang, Xiaoyu
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supporting information
p. 15 - 20
(2021/11/20)
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- Palladium-Catalyzed Asymmetric Markovnikov Hydroxycarbonylation and Hydroalkoxycarbonylation of Vinyl Arenes: Synthesis of 2-Arylpropanoic Acids
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Asymmetric hydroxycarbonylation is one of the most fundamental yet challenging methods for the synthesis of carboxylic acids. Herein, we reported the development of a palladium-catalyzed highly enantioselective Markovnikov hydroxycarbonylation of vinyl arenes with CO and water. A monodentate phosphoramidite ligand L6 plays vital role in the reaction. The reaction tolerates a range of functional groups, and provides a facile and atom-economical approach to an array of 2-arylpropanoic acids including several commonly used non-steroidal anti-inflammatory drugs. The catalytic system has also enabled an asymmetric Markovnikov hydroalkoxycarbonylation of vinyl arenes with alcohols to afford 2-arylpropanates. Mechanistic investigations suggested that the hydropalladation is irreversible and is the regio- and enantiodetermining step, while hydrolysis/alcoholysis is probably the rate-limiting step.
- Guan, Zheng-Hui,Ren, Zhi-Hui,Wang, Yuan,Yang, Hui-Yi,Yao, Ya-Hong,Zou, Xian-Jin
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supporting information
p. 23117 - 23122
(2021/09/18)
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- A general platinum-catalyzed alkoxycarbonylation of olefins
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Hydroxy- and alkoxycarbonylation reactions constitute important industrial processes in homogeneous catalysis. Nowadays, palladium complexes constitute state-of-the-art catalysts for these transformations. Herein, we report the first efficient platinum-catalysed alkoxycarbonylations of olefins including sterically hindered and functionalized ones. This atom-efficient catalytic transformation provides straightforward access to a variety of valuable esters in good to excellent yields and often with high selectivities. In kinetic experiments the activities of Pd- and Pt-based catalysts were compared. Even at low catalyst loading, Pt shows high catalytic activity.
- Beller, Matthias,Dühren, Ricarda,Franke, Robert,Ge, Yao,Huang, Weiheng,Jackstell, Ralf,Liu, Jiawang,Neumann, Helfried,Schneider, Carolin,Yang, Ji
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supporting information
p. 5235 - 5238
(2020/07/30)
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- Discovery of carboxyl-containing biaryl ureas as potent RORγt inverse agonists
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GSK805 (1) is a potent RORγt inverse agonist, but a drawback of 1 is its low solubility, leading to a limited absorption in high doses. We have explored detailed structure-activity relationship on the amide linker, biaryl and arylsulfonyl moieties of 1 trying to improve solubility while maintaining RORγt activity. As a result, a novel series of carboxyl-containing biaryl urea derivatives was discovered as potent RORγt inverse agonists with improved drug-like properties. Compound 3i showed potent RORγt inhibitory activity and subtype selectivity with an IC50 of 63.8 nM in RORγ FRET assay and 85 nM in cell-based RORγ-GAL4 promotor reporter assay. Reasonable inhibitory activity of 3i was also achieved in mouse Th17 cell differentiation assay (76percent inhibition at 0.3 μM). Moreover, 3i had greatly improved aqueous solubility at pH 7.4 compared to 1, exhibited decent mouse PK profile and demonstrated some in vivo efficacy in an imiquimod-induced psoriasis mice model.
- Sun, Nannan,Huang, Yafei,Yu, Mingcheng,Zhao, Yunpeng,Chen, Ji-An,Zhu, Chenyu,Song, Meiqi,Guo, Huimin,Xie, Qiong,Wang, Yonghui
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- COMPOUNDS AND METHODS FOR TREATMENT OF HEDGEHOG PATHWAY ASSOCIATED CONDITIONS
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Provided herein is novel compounds of formula (I), (II), (III), (IV), and (V) as described in the specification, and pharmaceutically acceptable salts, solvates, and prodrugs and compositions thereof, and methods of measuring hedgehog pathway activation in tumor cells, examining tumor cell proliferation, differentiation and apoptosis and using the compounds and pharmaceutical compositions disclosed for treatment of diseases and disorders associated with the hedgehog signaling pathway.
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Page/Page column 69; 70
(2020/01/24)
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- Total synthesis of carbazole alkaloids
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A Suzuki-Miyaura cross coupling, followed by triphenylphosphine mediated Cadogan reductive cyclization sequence provided efficient access to a series of carbazole alkaloids. In the present work, this approach was applied to the total synthesis of mukonine, clauszoline K, koenoline, murrayanine, murrayafoline A, mukoeic acid, glycoborine, glycozolicine, mukolidine, mukoline, glycozoline, 3-methoxy-9H-carbazole-1-carboxylic acid methyl ester, (3-methoxy-9H-carbazol-1-yl)-methanol, 3-methoxy-9H-carbazole-1-carbaldehyde, 3-methoxy-9H-carbazole-1-carboxylic acid, 2-methyl-9H-carbazole and nonsteroidal anti-inflammatory drug (NSAID) carprofen and its derivatives.
- Bhatthula, Bharath kumar goud,Kanchani, Janardhan reddy,Arava, Veera reddy,Subha
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p. 874 - 887
(2019/01/11)
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- Manganese catalyzed α-methylation of ketones with methanol as a C1 source
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The direct α-methylation of ketones with methanol under hydrogen borrowing conditions using a well-defined manganese PN3P complex as a pre-catalyst was, for the first time, achieved. The reactions typically proceed at 120 °C for 20 h with 3 mol% pre-catalyst loading and in the presence of NaOtBu (50 mol%) as base. The scope of the reaction was extended to the α-methylation of esters.
- Bruneau-Voisine, Antoine,Pallova, Lenka,Bastin, Stéphanie,César, Vincent,Sortais, Jean-Baptiste
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supporting information
p. 314 - 317
(2019/01/09)
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- Identification and Profiling of Hydantoins - A Novel Class of Potent Antimycobacterial DprE1 Inhibitors
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Tuberculosis is the leading cause of death worldwide from infectious diseases. With the development of drug-resistant strains of Mycobacterium tuberculosis, there is an acute need for new medicines with novel modes of action. Herein, we report the discovery and profiling of a novel hydantoin-based family of antimycobacterial inhibitors of the decaprenylphospho-β-d-ribofuranose 2-oxidase (DprE1). In this study, we have prepared a library of more than a 100 compounds and evaluated them for their biological and physicochemical properties. The series is characterized by high enzymatic and whole-cell activity, low cytotoxicity, and a good overall physicochemical profile. In addition, we show that the series acts via reversible inhibition of the DprE1 enzyme. Overall, the novel compound family forms an attractive base for progression to further stages of optimization and may provide a promising drug candidate in the future.
- Rogacki, Maciej K.,Pitta, Eleni,Balabon, Olga,Huss, Sophie,Lopez-Roman, Eva Maria,Argyrou, Argyrides,Blanco-Ruano, Delia,Cacho, Monica,Vande Velde, Christophe M. L.,Augustyns, Koen,Ballell, Lluis,Barros, David,Bates, Robert H.,Cunningham, Fraser,Van Der Veken, Pieter
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supporting information
p. 11221 - 11249
(2019/01/08)
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- INHIBITORS OF ACTIVIN RECEPTOR-LIKE KINASE
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Described herein are compounds that inhibit ALK2 and its mutants, pharmaceutical compositions including such compounds, and methods of using such compounds and compositions.
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- Stereodivergent coupling of aldehydes and alkynes via synergistic catalysis using Rh and Jacobsen's amine
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We report an enantioselective coupling between α-branched aldehydes and alkynes to generate vicinal quaternary and tertiary carbon stereocenters. The choice of Rh and organocatalyst combination allows for access to all possible stereoisomers with high enantio-, diastereo-, and regioselectivity. Our study highlights the power of catalysis to activate two common functional groups and provide access to divergent stereoisomers and constitutional structures.
- Cruz, Faben A.,Dong, Vy M.
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supporting information
p. 1029 - 1032
(2017/05/15)
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- Stereodivergent Coupling of Aldehydes and Alkynes via Synergistic Catalysis Using Rh and Jacobsen's Amine
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We report an enantioselective coupling between α-branched aldehydes and alkynes to generate vicinal quaternary and tertiary carbon stereocenters. The choice of Rh and organocatalyst combination allows for access to all possible stereoisomers with high ena
- Cruz, Faben A.,Dong, Vy M.
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supporting information
p. 1029 - 1032
(2021/09/04)
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- Stereoselective Ketone Rearrangements with Hypervalent Iodine Reagents
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The first stereoselective version of an iodine(III)-mediated rearrangement of arylketones in the presence of orthoesters is described. The reaction products, α-arylated esters, are very useful intermediates in the synthesis of bioactive compounds such as ibuprofen. With chiral lactic acid-based iodine(III) reagents product selectivities of up to 73 % ee have been achieved.
- Malmedy, Florence,Wirth, Thomas
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supporting information
p. 16072 - 16077
(2016/10/30)
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- HISTONE DEMETHYLASE INHIBITORS
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The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted pyrido[3,4-d]pyrimidin-4-one derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.
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Paragraph 00233
(2016/04/09)
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- Modulators of methyl modifying enzymes, compositions and uses thereof
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Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
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- Hydroesterification of styrene derivatives catalyzed by an acidic resin supporting palladium complexes
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Pd-TPPTS-OTPPTS (denoted as Pd-P-OP, where TPPTS was the sodium salt of tri(m-sulfophenyl)phosphine and OTPPTS was the oxidized form of TPPTS) complexes supported on acidic resins (denoted as Pd-P-OP/resin) were prepared and employed as versatile heterogeneous catalysts for the hydroesterification of vinyl-aromatics with alcohols. The catalysts were characterized by the methods of FT-IR, XPS, N2 physisorption, XRD, TGA, SEM and 31P NMR. According to the 31P NMR results, there was a weak coordination between OTPPTS and the Pd sites. Consequently, OTPPTS was a weak ligand to the Pd sites and thus dissociated easily, acting as a protective agent of the vacant coordination site of the Pd metal sites, which allowed the substrates more access to the metal sites. In the hydroesterification of styrene, the distribution of the branched and linear esters was remarkably impacted by adding an appropriate amount of OTPPTS and the acidic resin supports. A high yield and excellent selectivity towards the branched ester were obtained when OTPPTS and TPPTS were used in equimolar amounts under optimized reaction conditions. The generality and recyclability of the catalyst for the hydroesterification of vinyl-aromatics were also examined. In addition, the poisoning and hot filtration tests indicated that Pd(0) acted as the active species in a truly heterogeneous way. A Pd-hydride mechanism was proposed for the hydroesterification over the Pd-P-OP/LSI-600 catalyst. This journal is the Partner Organisations 2014.
- He, Zhenhong,Hou, Zhenshan,Luo, Yanping,Dilixiati, Yierxiati,Eli, Wumanjiang
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p. 1092 - 1103
(2014/04/03)
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- NOVEL PYRIMIDINE DERIVATIVE AND PHARMACEUTICAL COMPOSITION INCLUDING SAME AS AN ACTIVE INGREDIENT
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The present invention relates to a compound represented by formula (I) for inhibiting the activity of diacylglycerol O-acyltransferase type 1 (DGAT1), and pharmaceutically acceptable salts thereof, and a pharmaceutical composition comprising same as an active ingredient. The compound of the present invention may be used effectively in the treatment or prevention of a disease or condition mediated by the activity of DGAT1 such as obesity, type II diabetes, dyslipidemia, metabolic syndrome, and the like, without any adverse effects: wherein A, B, X, and R5 to R7 are the same as defined in the specification.
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- NOVEL PYRIMIDINE DERIVATIVE AND PHARMACEUTICAL COMPOSITION INCLUDING SAME AS AN ACTIVE INGREDIENT
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The present invention relates to a compound represented by formula (I) for inhibiting the activity of diacylglycerol O-acyltransferase type 1 (DGAT1), and pharmaceutically acceptable salts thereof, and a pharmaceutical composition comprising same as an active ingredient. The compound of the present invention may be used effectively in the treatment or prevention of a disease or condition mediated by the activity of DGAT1 such as obesity, type II diabetes, dyslipidemia, metabolic syndrome, and the like, without any adverse effects: wherein A, B, X, and R5 to R7 are the same as defined in the specification.
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- PDE 10a Inhibitors for the Treatment of Type II Diabetes
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Disclosed are compounds, compositions and methods for treating Type II diabetes. Such compounds are represented by Formula (I) as follows: wherein R1, R2, L, and Q are defined herein.
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- MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
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Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein
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- SUBSTITUTED PYRIMIDINES
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Disclosed are substituted pyrimidines useful as HIF prolyl hydroxylase inhibitors to treat anemia and like conditions.
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- SUBSTITUTED PYRIMIDINES
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The present invention relates to substituted pyrimidines useful as HIF prolyl hydroxylase inhibitors to treat anemia and like conditions.
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- The discovery of MK-0674, an orally bioavailable cathepsin K inhibitor
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MK-0674 is a potent and selective cathepsin K inhibitor from the same structural class as odanacatib with a comparable inhibitory potency profile against Cat K. It is orally bioavailable and exhibits long half-life in pre-clinical species. In vivo studies
- Isabel, Elise,Bateman, Kevin P.,Chauret, Nathalie,Cromlish, Wanda,Desmarais, Sylvie,Duong, Le T.,Falgueyret, Jean-Pierre,Gauthier, Jacques Yves,Lamontagne, Sonia,Lau, Cheuk K.,Leger, Serge,LeRiche, Tammy,Levesque, Jean-Francois,Li, Chun Sing,Masse, Frederic,McKay, Daniel J.,Mellon, Christophe,Nicoll-Griffith, Deborah A.,Oballa, Renata M.,Percival, M. David,Riendeau, Denis,Robichaud, Joel,Rodan, Gideon A.,Rodan, Sevgi B.,Seto, Carmai,Therien, Michel,Truong, Vouy Linh,Wesolowski, Gregg,Young, Robert N.,Zamboni, Robert,Black, W. Cameron
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scheme or table
p. 887 - 892
(2010/08/22)
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- Oxidative rearrangements of arylalkanones with 1H-1-hydroxy-5-methyl-1,2,3-benziodoxathiole 3,3-dioxide, a 'green' analog of Koser's reagent
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Previous methods for the conversion of arylalkanones to alkyl 2-arylesters by oxidative rearrangement utilized reagents which either produced toxic metal salts or halogenated organics as by-products. In this report, 1H-1-hydroxy-5-methyl-1,2,3-benziodoxathiole 3,3-dioxide (HMBI) is used to effect this useful transformation, where the reduced iodine reagent is water-soluble and readily recycled.
- Justik, Michael W.
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p. 3003 - 3007
(2008/02/06)
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- CATHEPSIN CYSTEINE PROTEASE INHIBITORS
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This invention relates to a novel class of compounds, represented by the formula below, wherein the meanings of G, E, E, n, R1, R2, R3 et R4 are indicated therein, which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.
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Page/Page column 63
(2010/02/11)
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- Diethylaminosulphur Trifluoride (DAST) as an Effective Reagent for Preparation of Methyl 2-Arylpropanoates from 1-Aryl-1,1-dimethoxypropan-2-ols
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Treatment of dimethylacetals of aryl 1-hydroxyethyl ketones (Ar= Ph, 4-PhC6H4, 4-BuiC6H4, 4-MeOC6H4, 4-BrC6H4, 6-MeOnaphthalen-2-yl) with diethylaminosulphur trifluoride (DAST) affords smoothly the methyl 2-arylpropanoates in good yield via aryl-group migration.On the other hand, treatment of aryl 1-hydroxyethyl ketones with DAST gives the corresponding aryl 1-fluoroethyl ketones (Ar= Ph, 4-PhC6H4, 4-BuiC6H4) in high yield.
- Yamauchi, Takayoshi,Hattori, Kaneaki,Ikeda, Shun-ichi,Tamaki, Kentaro
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p. 1683 - 1685
(2007/10/02)
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- A FACILE TRANSFORMATION OF ALKYL ARYL KETONES TO METHYL α-ARYLALKANOATES BY ANODIC OXIDATION IN THE PRESENCE OF IODINE OR IODO COMPOUNDS.
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Anodic oxidation of easily accessible alkyl aryl ketones 1 in trimethyl orthoformate containing a small amount of iodine or organo-iodo compounds gave methyl α-arylalkanoates 2 in high yields.
- Shono, Tatsuya,Matsumura, Yoshihiro,Katoh, Susumu,Fujita, Tetsuhiro,Kamada, Tohru
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p. 371 - 374
(2007/10/02)
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- Thallium(III) Nitrate-mediated Efficient Synthesis of 2-Arylpropionic Acids from 1-Halogenoethyl Aryl Ketones
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Treatment of 1-halogenoethyl aryl ketones (1; R = H, iBu, OMe, Me, Ph, or Br; X = Br or Cl) with Tl(NO3)3*3H2O and perchloric acid in a trialkyl orthoformate at 25-50 deg C affords alkyl esters (3) of 2-arylpropionic acid in good-to-excellent yields via 1,2-aryl migration in substrates (1).The hydrolysis of esters (3) leads to the corresponding acids, some of which are pharmaceutically important compounds.The reaction hardly occurs in methanol.The key step of the reaction is the in situ acetal formation of the starting ketone.The thallium(III) salt acts as an effective Lewis acid catalyst for both acetal formation and halide abstraction.
- Yamauchi, Takayoshi,Nakao, Kenji,Fujii, Kyoichi
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p. 1255 - 1258
(2007/10/02)
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- Oxidative Rearrangement of Aryl Ethyl Ketones to Alkyl 2-Arylpropanoates by Lead(IV) Acetate
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Treatment of the propiophenones p-R'C6H4COCH2Me (1; R' = H, Me, Bui, Ph, Br) with lead(IV) acetate in trialkyl orthoformate in the presence of acid catalyst is found to give alkyl esters of 2-arylpropanoic acids (2) in good to excellent yields via 1,2-aryl migration in (1).Hydrolysis of (2) leads to the corresponding acids, some of which are important pharmaceutical compounds.The rate of aryl migration increases when the substituent R' is an electron-releasing group such as methyl, isobutyl, or phenyl.The rate of rearrangement of the dimethyl acetals of (1); R' = H, Bui, Ph) is nearly the same as that of (1).Such rearrangement hardly occurs in the absence of acid catalyst.A reaction pathway involving the formation of a monoalkoxylead(IV) compound, and its decomposition accompanied with aryl migration is discussed.
- Yamauchi, Takayoshi,Nakao, Kenji,Fujii, Kyoichi
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p. 1433 - 1436
(2007/10/02)
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- Preparation of Methyl 2-Arylpropanoates by the Reaction of 2-Hydroxypropiophenone Dimethyl Acetals with Sulfuryl Chloride in the Presence of an Amide or a Weak Base
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Treatment of 2-hydroxypropiophenone dimethyl acetals (1; R=H, i-Bu, OMe, Ph, Br) with sulfuryl chloride in the presence of an amide or a weak base affords methyl 2-arylpropanoates (2) in good to excellent yields via 1,2-aryl migration of 1.The hydrolysis of 2 leads to the corresponding acids some of which are pharmaceutically important compounds having nonsteroidal anti-inflammatory and analgesic acivities.The aryl migration proceeds stereospecifically with complete inversion of configuration at the β-carbon atom.
- Yamauchi, Takayoshi,Hattori, Kaneaki,Nakao, Kenji,Tamaki, Kentaro
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p. 4015 - 4018
(2007/10/02)
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