- Structure-based linker optimization of 6-(2-cyclohexyl-1-alkyl)-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones as potent non-nucleoside HIV-1 reverse transcriptase inhibitors
-
In continuation of our efforts toward the discovery of potent HIV-1 NNRTIs with diverse structures, a series of novel S-DACO analogues of 6-(2-cyclohexyl-1-alkyl)-2-(2-oxo-2-phenyl-ethylsulfanyl)pyrimidin-4(3H)-ones were designed, synthesized and evaluated for their antiviral activities in MT-4 cells. Most of these new compounds showed moderate to good activities against wild type HIV-1 with IC50 values ranging from 7.55 μmol/L to 0.018 μmol/L. Among them, compound 5c was identified as the most promising inhibitor against HIV-1 replication with an IC50 = 0.018 μmol/L, CC50 = 194 μmol/L, and SI = 12791, which was much more potent than the reference drugs NVP and DLV and comparable to AZT and EFV. In addition, 5c also exhibited improved activity against double mutant HIV-1 strain RES056 compared to that of the reference drugs NVP/DLV and DB02. The preliminary structure-activity relationship (SAR) and molecular modeling studies were also discussed, which provides some useful indications for guiding the further rational design of new S-DACO analogues.
- Li, Daxiong,Zhang, Chunsheng,Ding, Wei,Huang, Siming,Yu, Le,Lu, Nan,Pan, Wenkai,Li, Yiming,De Clercq, Erik,Pannecouque, Christophe,Zhang, Hongbing,Wang, Yueping,He, Yanping,Chen, Fener
-
supporting information
p. 1020 - 1024
(2020/10/12)
-
- Aromatic compound hydrogenation and hydrodeoxygenation method and application thereof
-
The invention belongs to the technical field of medicines, and discloses an aromatic compound hydrogenation and hydrodeoxygenation method under mild conditions and application of the method in hydrogenation and hydrodeoxygenation reactions of the aromatic compounds and related mixtures. Specifically, the method comprises the following steps: contacting the aromatic compound or a mixture containing the aromatic compound with a catalyst and hydrogen with proper pressure in a solvent under a proper temperature condition, and reacting the hydrogen, the solvent and the aromatic compound under the action of the catalyst to obtain a corresponding hydrogenation product or/and a hydrodeoxygenation product without an oxygen-containing substituent group. The invention also discloses specific implementation conditions of the method and an aromatic compound structure type applicable to the method. The hydrogenation and hydrodeoxygenation reaction method used in the invention has the advantages of mild reaction conditions, high hydrodeoxygenation efficiency, wide substrate applicability, convenient post-treatment, and good laboratory and industrial application prospects.
- -
-
Paragraph 0094-0096; 0098; 0100-0104
(2021/05/29)
-
- Synthetic method of acid compound
-
The invention belongs to the field of organic synthesis, and particularly relates to a synthetic method of an acid compound. An acid anhydride compound and an alkyl bromide or a functionalized alkyl bromide are subjected to a cross-electrophilic coupling reaction to synthesize an acid compound, so that the application of the alkyl bromide in the cross-electrophilic coupling reaction is expanded, and a novel non-traditional method for chemically and selectively constructing a carbon-carbon bond through a decarburization process is provided. The synthesis method is simple, economic, green and environment-friendly, and has wider applicability or is suitable for large-scale production.
- -
-
Paragraph 0028-0033; 0042
(2020/08/25)
-
- Catalytic hydrogenation of cinnamic acid and salicylic acid
-
Hydrogenation of cinnamic acid and salicylic acid was carried out using 5 %Ru/C, 5 % Pd/C and Ru-Sn/Al2O3 catalyst at 493 K and 6.89 MPa of hydrogen partial pressure. Ru-Sn/Al2O3 catalyst was found to be active for hydrogenation -COOH group to give cinnamyl alcohol. The selectivity to cinnamyl alcohol was low (15 %) as absolute inhibition of C=C bond hydrogenation in cinnamic acid is challenging. 5 %Pd/C catalyst was found to hydrogenate C=C bond and aromatic ring in cinnamic acid. 5 %Ru/C catalyst was found to be least selective catalyst as it hydrogenated C=C bond, aromatic ring and -COOH group in cinnamic acid. Hydrogenation of salicylic acid is not possible at 493 K as decarboxylation of salicylic acid occurs.
- Shinde, Sunil B.,Deshpande, Raj M.
-
p. 339 - 341
(2020/01/08)
-
- Preparation method for synthesizing propiolic acid and derivatives thereof
-
The invention provides a preparation method for synthesizing propiolic acid and derivatives thereof. The synthetic route of the method comprises the following steps: firstly, under anhydrous and anaerobic conditions, adding magnesium metal, elemental iodine and a solvent into a reactor, uniformly stirring the reactants, and then dropwise adding halogenated hydrocarbon to react to generate a hydrocarbyl magnesium halide Grignard reagent; dropwise adding terminal alkyne into the reactor for Grignard exchange reaction to obtain alkynyl magnesium halide; and finally, introducing CO2 into the reactor, carrying out nucleophilic addition reaction, and hydrolyzing the product to obtain the propiolic acid compound. The preparation method provided by the invention is simple, safe and mild in operation condition.
- -
-
Paragraph 0016
(2020/10/14)
-
- Mechanistic study of the selective hydrogenation of carboxylic acid derivatives over supported rhenium catalysts
-
The structure and performance of TiO2-supported Re (Re/TiO2) catalysts for selective hydrogenation of carboxylic acid derivatives have been investigated. Re/TiO2 promotes selective hydrogenation reactions of carboxylic acids and esters that form the corresponding alcohols, and of amides that generate the corresponding amines. These processes are not accompanied by reduction of aromatic moieties. A Re loading amount of 5 wt% and a catalyst pretreatment with H2 at 500 °C were identified as being optimal to obtain the highest catalytic activity for the hydrogenation processes. The results of studies using various characterization methods, including X-ray diffraction (XRD), X-ray absorption fine structure (XAFS), X-ray photoelectron spectroscopy (XPS), and scanning transmission electron microscopy (STEM), indicate that the Re species responsible for the catalytic hydrogenation processes have sub-nanometer to a few nanometer sizes and average oxidation states higher than 0 and below +4. The presence of either a carboxylic acid and/or its corresponding alcohol is critical for preventing the Re/TiO2 catalyst from promoting production of dearomatized byproducts. Although Re/TiO2 is intrinsically capable of hydrogenating aromatic rings, carboxylic acids, alcohols, amides, and amines strongly adsorb on the Re species, which leads to suppression of this process. Moreover, the developed catalytic system was applied to selective hydrogenation of triglycerides that form the corresponding alcohols.
- Toyao, Takashi,Ting, Kah Wei,Siddiki, S. M. A. Hakim,Touchy, Abeda S.,Onodera, Wataru,Maeno, Zen,Ariga-Miwa, Hiroko,Kanda, Yasuharu,Asakura, Kiyotaka,Shimizu, Ken-ichi
-
p. 5413 - 5424
(2019/10/29)
-
- Pd-Catalyzed Highly Chemo- And Regioselective Hydrocarboxylation of Terminal Alkyl Olefins with Formic Acid
-
An efficient Pd-catalyzed hydrocarboxylation of alkenes with HCOOH is described. A wide variety of linear carboxylic acids bearing various functional groups can be obtained with excellent chemo- and regioselectivities under mild reaction conditions. The reaction process is operationally simple and requires no handling of toxic CO.
- Ren, Wenlong,Chu, Jianxiao,Sun, Fei,Shi, Yian
-
supporting information
p. 5967 - 5970
(2019/08/26)
-
- Synthetic method of terminal carboxylic acid
-
The invention discloses a synthetic method of a terminal carboxylic acid. The synthetic method is characterized by comprising the steps of adding an olefin represented by a formula (3) shown in the description, formic acid, acetic anhydride, Pd(OAc)2 and a monophosphorus ligand TFPP into an organic solvent in a proportion, carrying out hydrogen carbonylation reaction on the olefin represented by the formula (3) shown in the description, formic acid and acetic anhydride at 80-90 DEG C for 48h-72h under the catalysis of the metal palladium salt Pd(OAc)2 and the monophosphorus ligand TFPP so as to obtain the terminal carboxylic acid represented by a formula shown in the description, and separating a target product, namely the terminal carboxylic acid after the reaction is finished, wherein olefin represented by the formula (3) is selected from cycloolefins, or linear olefins of which the R1 is electron donating groups. By virtue of the method disclosed by the invention, corresponding terminal carboxylic acid and a derivative thereof can be prepared through the reaction under mild conditions of low temperature and no high pressure; and the steps of the synthetic method are simple and convenient, the operation is convenient, the yield is high, the energy source can be greatly saved, and the synthetic efficiency can be greatly improved.
- -
-
Paragraph 0099-0102
(2019/11/21)
-
- Carbonylative Transformation of Allylarenes with CO Surrogates: Tunable Synthesis of 4-Arylbutanoic Acids, 2-Arylbutanoic Acids, and 4-Arylbutanals
-
In this Communication, procedures for the selective synthesis of 4-arylbutanoic acids, 2-arylbutanoic acids, and 4-arylbutanals from the same allylbenzenes have been developed. With formic acid or TFBen as the CO surrogate, reactions proceed selectively and effectively under carbon monoxide gas-free conditions.
- Wu, Fu-Peng,Li, Da,Peng, Jin-Bao,Wu, Xiao-Feng
-
supporting information
p. 5699 - 5703
(2019/08/01)
-
- Method for synthesizing 3-cyclohexyl propionic acid
-
The invention discloses a method for synthesizing 3-cyclohexylpropionic acid, and relates to the 3-cyclohexylpropionic acid. The method comprises the following steps: adding a silver carbon catalyst into an alkaline solution, adding cinnamaldehyde, filtering out the silver carbon catalyst after oxidation reaction, wherein the filtrate is a cinnamate mixed solution; transferring the cinnamate mixedsolution into a hydrogenation reaction kettle, introducing hydrogen under the catalysis of a ruthenium carbon catalyst, heating to carry out hydrogenation reaction, filtering out the ruthenium carboncatalyst, acidifying the filtrate with acid until the pH value is 2-3, and standing and layering to obtain the 3-cyclohexylpropionic acid. Oxidizing the reaction solution with the cinnamaldehyde without post-treatment, and directly carrying out hydrogenation reaction to obtain 3-cyclohexylpropionic acid; the total yield can be more than 90%. The reaction liquid obtained after the oxidation reaction is directly used by the oxidation reaction liquid without the treatment of acidification, washing, decolorization, purification and the like;according to the new method for synthesizing the 3-cyclohexylpropionic acid by hydrogenation technology, the synthesis cost of 3-cyclohexylpropionic acid can be significantly saved.
- -
-
Paragraph 0025-0033
(2019/06/30)
-
- Organocatalyzed Aerobic Oxidation of Aldehydes to Acids
-
The first example organocatalyzed aerobic oxidation of aldehydes to carboxylic acids in both organic solvent and water under mild conditions is developed. As low as 5 mol % N-hydroxyphthalimide was used as the organocatalyst, and molecular O2 was used as the sole oxidant. No transition metals or hazardous oxidants or cocatalysts were involved. A wide range of carboxylic acids bearing diverse functional groups were obtained from aldehydes, even from alcohols, in high yields.
- Dai, Peng-Fei,Qu, Jian-Ping,Kang, Yan-Biao
-
supporting information
p. 1393 - 1396
(2019/02/26)
-
- A aldehyde or mellow directly converted into the carboxylic acid (by machine translation)
-
The invention discloses a aldehyde or mellow oxidation can be directly transformed into carboxylic acid, is characterized in that the pure oxygen environment, in N - hydroxy imide compound under the catalysis of the imide compound or N - hydroxy and nitrous acid ester compound common under the catalysis, the CH2 OH and CHO oxidation directly converted into the carboxylic acid compounds. The invention using oxygen as the oxidizing agent, does not add any metal catalyst, environment-friendly, high catalytic efficiency, simple and convenient operation. With the previous metal catalytic system complex and different catalytic system, has some metal catalytic system in the process, the use of transition metal will cause the transition metal of the residual, the invention adopts the non-metallic catalytic system, environmental protection, preventing the metal residue problem, this to the solution of the drug in the synthesis of transition metal residue problem and provides a new method of thinking. (by machine translation)
- -
-
Paragraph 0039; 0040
(2018/08/03)
-
- CATALYTIC CARBOXYLATION OF ACTIVATED ALKANES AND/OR OLEFINS
-
The present invention relates to a method of reacting starting materials with an activating group, namely alkanes carrying a leaving group and/or olefins, with carbon dioxide under transition metal catalysis to give carboxyl group-containing products. It is a special feature of the method of the present invention that the carboxylation predominantly takes place at a preferred position of the molecule irrespective of the position of the activating group. The carboxylation position is either an aliphatic terminus of the molecule or it is a carbon atom adjacent to a carbon carrying an electron withdrawing group. The course of the reaction can be controlled by appropriately choosing the reaction conditions to yield the desired regioisomer.
- -
-
Page/Page column 65; 66
(2018/02/28)
-
- TiO2-Supported Re as a General and Chemoselective Heterogeneous Catalyst for Hydrogenation of Carboxylic Acids to Alcohols
-
TiO2-supported Re, Re/TiO2, was found to promote selective hydrogenation of carboxylic acids having aromatic and aliphatic moieties to the corresponding alcohols. Re/TiO2showed superior results compared to other transition-metal-loaded TiO2and supported Re catalysts for selective hydrogenation of 3-phenylpropionic acid. 3-phenylpropanol was produced in 97 % yield under mild conditions (5 MPa H2at 140 °C). Contrary to typical heterogeneous catalysts, Re/TiO2does not lead to the formation of dearomatized byproducts. The catalyst is recyclable and shows a wide substrate scope in the synthesis of alcohols (22 examples; up to 97 % isolated yield).
- Toyao, Takashi,Siddiki, S. M. A. Hakim,Touchy, Abeda S.,Onodera, Wataru,Kon, Kenichi,Morita, Yoshitsugu,Kamachi, Takashi,Yoshizawa, Kazunari,Shimizu, Ken-Ichi
-
supporting information
p. 1001 - 1006
(2017/02/05)
-
- Rhenium-Loaded TiO2: A Highly Versatile and Chemoselective Catalyst for the Hydrogenation of Carboxylic Acid Derivatives and the N-Methylation of Amines Using H2 and CO2
-
Herein, we report a heterogeneous TiO2-supported Re catalyst (Re/TiO2) that promotes various selective hydrogenation reactions, which includes the hydrogenation of esters to alcohols, the hydrogenation of amides to amines, and the N-methylation of amines, by using H2 and CO2. Initially, Re/TiO2 was evaluated in the context of the selective hydrogenation of 3-phenylpropionic acid methyl ester to afford 3-phenylpropanol (pH2 =5 MPa, =5 MPa, T=180 °C), which revealed a superior performance over other catalysts that we tested in this study. In contrast to other typical heterogeneous catalysts, hydrogenation reactions with Re/TiO2 did not produce dearomatized byproducts. DFT studies suggested that the high selectivity for the formation of alcohols in favor of the hydrogenation of aromatic rings is ascribed to the higher affinity of Re towards the COOCH3 group than to the benzene ring. Moreover, Re/TiO2 showed a wide substrate scope for the hydrogenation reaction (19 examples). Subsequently, this Re/TiO2 catalyst was applied to the hydrogenation of amides, the N-methylation of amines, and the N-alkylation of amines with carboxylic acids or esters.
- Toyao, Takashi,Siddiki,Morita, Yoshitsugu,Kamachi, Takashi,Touchy, Abeda S.,Onodera, Wataru,Kon, Kenichi,Furukawa, Shinya,Ariga, Hiroko,Asakura, Kiyotaka,Yoshizawa, Kazunari,Shimizu, Ken-Ichi
-
supporting information
p. 14848 - 14859
(2017/10/27)
-
- Site-Selective Catalytic Carboxylation of Unsaturated Hydrocarbons with CO2 and Water
-
A catalytic protocol that reliably predicts and controls the site-selective incorporation of CO2 to a wide range of unsaturated hydrocarbons utilizing water as formal hydride source is described. This platform unlocks an opportunity to catalytically repurpose three abundant, orthogonal feedstocks under mild conditions.
- Gaydou, Morgane,Moragas, Toni,Juliá-Hernández, Francisco,Martin, Ruben
-
supporting information
p. 12161 - 12164
(2017/09/12)
-
- Remote carboxylation of halogenated aliphatic hydrocarbons with carbon dioxide
-
Catalytic carbon-carbon bond formation has enabled the streamlining of synthetic routes when assembling complex molecules. It is particularly important when incorporating saturated hydrocarbons, which are common motifs in petrochemicals and biologically relevant molecules. However, cross-coupling methods that involve alkyl electrophiles result in catalytic bond formation only at specific and previously functionalized sites. Here we describe a catalytic method that is capable of promoting carboxylation reactions at remote and unfunctionalized aliphatic sites with carbon dioxide at atmospheric pressure. The reaction occurs via selective migration of the catalyst along the hydrocarbon side-chain with excellent regio- and chemoselectivity, representing a remarkable reactivity relay when compared with classical cross-coupling reactions. Our results demonstrate that site-selectivity can be switched and controlled, enabling the functionalization of less-reactive positions in the presence of a priori more reactive ones. Furthermore, we show that raw materials obtained in bulk from petroleum processing, such as alkanes and unrefined mixtures of olefins, can be used as substrates. This offers an opportunity to integrate a catalytic platform en route to valuable fatty acids by transforming petroleum-derived feedstocks directly.
- Juliá-Hernández, Francisco,Moragas, Toni,Cornella, Josep,Martin, Ruben
-
-
- Hydrogen Self-Sufficient Arene Reduction to Cyclohexane Derivatives Using a Combination of Platinum on Carbon and 2-Propanol
-
Various arenes have been hydrogenated using platinum on carbon in a 2-propanol-aqueous mixed solvent at 100 C without the addition of flammable hydrogen gas to give the corresponding cyclohexane derivatives. 2-Propanol plays a role as an efficient hydrogen source based on the platinum on carbon-catalyzed dehydrogenation.
- Sawama, Yoshinari,Mori, Misato,Yamada, Tsuyoshi,Monguchi, Yasunari,Sajiki, Hironao
-
supporting information
p. 3667 - 3670
(2016/01/25)
-
- Hydrogenation of coumarin to octahydrocoumarin over a Ru/C catalyst
-
The production of octahydrocoumarin, which can serve as a replacement for toxic coumarin, was investigated using 5% Ru on active carbon (Ru/C) as the catalyst for the hydrogenation of coumarin. The hydrogenation was studied by optimizing the reaction conditions (pressure, solvent and coumarin concentration). The activity and selectivity of the Ru/C catalyst were compared for different solvents. The mechanism of coumarin hydrogenation was deduced. The formation of side products was explained. The optimal hydrogenation reaction conditions were: 130 °C, 10 MPa, 60 wt% coumarin in methanol, and 0.5 wt% (based on coumarin) of Ru/C catalyst. At the complete conversion of coumarin, the selectivity to the desired product was 90%.
- Bílková, Dana,Jansa, Petr,Paterová, Iva,?erveny, Libor
-
p. 957 - 960
(2015/07/01)
-
- A NiPdB-PEG(800) amorphous alloy catalyst for the chemoselective hydrogenation of electron-deficient aromatic substrates
-
A new Pd and polyethylene glycol 800 [PEG(800)]-modified NiB [NiPdB-PEG(800)] amorphous alloy catalyst was prepared, which demonstrated excellent activities, similar to those of noble metal catalysts, in the chemoselective hydrogenation of a series of electron-deficient aromatic substrates in water. The addition of small amounts of Pd to NiB markedly improved its activity. The Pd not only benefits the dispersion of active species but also contributes to the activity of the catalyst. The accompanying agglomeration can be inhibited with the further addition of PEG(800), which results in the largest surface area, the smallest particle size, and the greatest number of active species, resulting in optimum H2- chemisorption and accounting for its highest activity. The key factors determining the main reaction products depend not only on the structures of the substrates but also on the character of the solvents. Water is found to be the most effective solvent for most of the substrates. Disperse and be active! A Pd and polyethylene glycol 800 [PEG(800)]-modified NiB [NiPdB-PEG(800)] amorphous alloy catalyst demonstrates excellent activities, similar to those of noble metal catalysts, in the chemoselective hydrogenation of a series of electron-deficient aromatic substrates in water. The addition of Pd benefits the dispersion of active species and contributes to the activity of the catalyst. Copyright
- Bai, Guoyi,Zhao, Zhen,Dong, Huixian,Niu, Libo,Wang, Yalong,Chen, Qingzhi
-
p. 655 - 662
(2014/03/21)
-
- Synthesis of l -octaarginine through microencapsulated palladium-catalyzed allyl ester deprotection
-
Octaarginine has been described as a molecular transporter. We report a useful synthesis of orthogonally protected l-octaarginine by using a method based on a microencapsulated palladium catalyst. Known palladium-based methods for allyl ester deprotection have been modified to facilitate purification of the unprotected intermediates. This improvement in the purification step has also been tested with a variety of allyl α-amino esters and allyl α,β-unsaturated esters.
- Pérez-López, Ana M.,González-Calderón, Dávir,Occorso, Antonio,Galindo-ángel, Javier,Domínguez-Seglar, José F.,Tamayo, Juan A.,Díaz-Gavilán, Mónica,Gómez-Vidal, José A.
-
supporting information
p. 2319 - 2322
(2015/08/06)
-
- Facile palladium-catalyzed hydrocarboxylation of olefins without external CO gas
-
An effective Pd-catalyzed hydrocarboxylation of olefins with phenyl formate and formic acid is described. A variety of carboxylic acids are obtained in good yields with high regioselectivities under operationally simple conditions without the use of toxic CO gas.
- Wang, Yang,Ren, Wenlong,Li, Jingfu,Wang, Haining,Shi, Yian
-
supporting information
p. 5960 - 5963
(2015/02/19)
-
- Aqueous phase hydrogenation of substituted phenyls over carbon nanofibre and activated carbon supported Pd
-
The hydrogenation of aromatic acids and other substituted phenyls has been studied for two palladium-based catalysts; one supported on carbon nanofibres (CNFs) and the other on a steam-activated carbon. The reactions were conducted in both aqueous solution and aprotic organic solvents. The major product over both catalysts was the same irrespective of the substrate indicating that support characteristics and Pd dispersion play at most only a minor role in defining the reaction pathway. The key factor in determining the major reaction product resulting from either preferential hydrogenation of the aromatic ring, or reaction of the external functional group, was the extent to which the external group interacted with water molecules which acted in some cases to protect the external function from interaction with the metal surface and induced selective reduction of the aromatic ring.
- Anderson,Athawale,Imrie,McKenna,McCue,Molyneux,Power,Shand,Wells
-
experimental part
p. 9 - 15
(2010/06/12)
-
- One-pot conversion of alkyl aldehydes into substituted propanoic acids via Knoevenagel condensation with Meldrum's acid
-
Reaction of a range of alkyl aldehydes and Meldrum's acid in triethylammonium formate (TEAF) at 100 °C generates substituted propanoic acids in a single step.
- Mudhar, Harminder,Witty, Andrew
-
experimental part
p. 4972 - 4974
(2011/01/12)
-
- A novel crystallization-induced diastereomeric transformation based on a reversible carbon-sulfur bond formation. Application to the synthesis of a γ-secretase inhibitor
-
(Chemical Equation Presented) This paper describes a remarkably efficient process for the preparation of γ-secretase inhibitor 1. The target is synthesized in only five steps with an overall yield of 58%. The key operation is a highly selective and practical, crystallization-driven transformation for the conversion of a mixture of tertiary benzylic alcohols into the desired sulfide diastereomer with 94:6 dr. This unprecedented process is based upon a reversible carbon-sulfur bond formation under acidic conditions.
- Davies, Antony J.,Scott, Jeremy P.,Bishop, Brian C.,Brands, Karel M. J.,Brewer, Sarah E.,DaSilva, Jimmy O.,Dormer, Peter G.,Dolling, Ulf-H.,Gibb, Andrew D.,Hammond, Deborah C.,Lieberman, David R.,Palucki, Michael,Payack, Joseph F.
-
p. 4864 - 4871
(2008/02/05)
-
- Indium-mediated chemoselective deprotection and demonochlorination of 2,2,2-trichloroethyl esters
-
On treatment with indium metal, the 2,2,2-trichloroethyl carboxylates smoothly undergo deprotection to carboxylic acids and reductive demonochlorination to 2,2-dichloroethyl esters, sharply depending on their structures.
- Mineno, Tomoko,Kansui, Hisao,Kunieda, Takehisa
-
p. 5027 - 5030
(2008/02/10)
-
- Protease inhibitors
-
The present invention provides 4-amino-azepan-3-one protease inhibitors and pharmaceutically acceptable salts, hydrates and solvates thereof which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, novel intermediates of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis; gingival disease including gingivitis and periodontitis; arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia of malignancy; and metabolic bone disease, comprising inhibiting said bone loss or excessive cartilage or matrix degradation by administering to a patient in need thereof a compound of the present invention.
- -
-
-
- Protease inhibitors
-
The present invention provides 4-amino-azepan-3-one protease inhibitors and pharmaceutically acceptable salts, hydrates and solvates thereof which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, novel intermediates of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis; gingival disease including gingivitis and periodontitis; arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia of malignancy; and metabolic bone disease, comprising inhibiting said bone loss or excessive cartilage or matrix degradation by administering to a patient in need thereof a compound of the present invention.
- -
-
-
- A simple and highly efficient deprotecting method for methoxymethyl and methoxyethoxymethyl ethers and methoxyethoxymethyl esters
-
A series of methoxyethoxymethyl (MEM)- and methoxymethyl (MOM)-ethers and MEM-esters were hydrolyzed to their corresponding alcohols and carboxylic acids by a catalytic amount of CBr4 (10%) in iPrOH under refluxing reaction condition. The chemoselective hydrolysis between R3Si- and MEM-protected alcohols can be achieved by using different steric bulkness solvents such as MeOH or iPrOH.
- Shih-Yuan Lee, Adam,Hu, Yi-Jung,Chu, Shu-Fang
-
p. 2121 - 2126
(2007/10/03)
-
- Metallacyclische Acyl-carboxylate des Nickels: Reaktivitaet der Acylgruppe und Synthesepotential bei Kreuzkopplungsreaktionen mit Alkylhalogeniden
-
2-Cyclohexene-1,2-dicarboxylic acid-anhydride reacts with electron-rich nickel(0) centres to form nickel(0) complexes, whereas the isomeric 4-cyclohexene-1,2-dicarboxylic acid-anhydride reacts with ring opening of the anhydride to yield thermally stable acyl-carboxylato-nickel(II) compounds.The structure of a typical compound with (TMED)Ni0 as a complex fragment was determined by single crystal X-ray structural analysis, the crystal also containing the product of CO-elimination, the nickelalactone.The cross-coupling reaction of metallacyclic acyl-carboxylato complexes of Ni with R-X can be used for the formation of side chains of steroids containing γ-ketocarboxylic acids.These compounds are interesting precursors for the preparation of analogues of vitamin D3 metabolites.
- Fischer, Reinald,Walther, Dirk,Kempe, Rhett,Sieler, Joachim,Schoenecker, Bruno
-
p. 131 - 136
(2007/10/02)
-
- Origins of stereoselectivity in radical additions: Reactions of alkenes and radicals bearing oxazolidine and thiazolidine amide groups
-
Single-crystal X-ray analysis of four alkenes that undergo stereoselective radical addition reactions are reported. The facial selectivity of radical additions to these alkenes is understood based upon their solid-state conformations. Alkenes which have a conformation placing a group at a position in space sterically protecting one of the faces from addition undergo radical addition with diastereofacial selectivity. The structures of the alkenes are analyzed by the polar coordinates of groups relative to the alkene center undergoing addition. The analysis of conformations of alkenes also provides a rationale for stereoselectivity in the reactions of radicals derived from the alkenes. Factors which influence the conformation of the alkene also apparently influence the conformation of analogous radicals. Several products of addition were also subjected to X-ray cryslallographic analysis, and the steric factors which influence the conformation of the reactant alkene are also observed to affect the conformation of the radical addition products.
- Porter, Ned A.,Rosenstein, Ian J.,Breyer, Robert A.,Bruhnke, John D.,Wu, Wen-Xue,McPhail, Andrew T.
-
p. 7664 - 7676
(2007/10/02)
-
- Nickelalactone als Synthesebausteine: Sonochemische und Bimetallsktivierung der Kreuzkopplungsreaction mit Alkyl-halogeniden
-
Nickelalactones with five- and six-membered chelate ring structures can be synthesized in a simple one-pot reaction, starting from Ni(acac)2, bipy, Et3Al and cyclic anhydrides.In the presence of MnI2 and by activation with ultrasound they react selectively with alkyl iodides in cross coupling reactions.The reason for the activating effect of MnI2 is the formation of bimetallic complexes.Many reactive functional groups (e.g.COOR, CHO, CN) can be tolerated.Therefore the cross coupling reaction is of preparative value in the synthesis of functionalized carboxylic acids.
- Fischer, Reinald,Walther, Dirk,Braeunlich, Gabriele,Undeutsch, Bernd,Ludwig, Werner
-
p. 395 - 407
(2007/10/02)
-
- A nickelacycle as propionic acid equivalent for carbon-carbon coupling reactions; application to the synthesis of C25 steroid carboxylic acids
-
β-Substituted propionic acids are prepared in good yields by carbon-carbon coupling reaction of the nickelacycle 1 with organic iodides and anhydrous manganese(II) iodide. This new reaction is used to the synthesis of C25 steroid carboxylic acids from C22 steroid iodides.
- Schonecker,Walther,Fischer,Nestler,Braunlich,Eibisch,Droescher
-
p. 1257 - 1260
(2007/10/02)
-
- Metal Alkoxide Modified Organometallic Reagents. Preparation and Stability of Organolithium Reagents in Tetrahydrofuran in the Presence of Magnesium 2-Ethoxyethoxide
-
The metalating ability of alkyllithium reagents and their tendency to cleave THF are greatly diminished in the presence of magnesium 2-ethoxyethoxide, 1.Advantage may be taken of this to generate organolithium reagents in THF in the presence of 1 under conditions not normally favorable to their stability.Thus, by reaction with metallic lithium in the presence of 1 in THF, the compounds RX (R = n-Bu, s-Bu, t-Bu, cyclohexyl, menthyl, p-methoxyphenyl, o-(methoxymethyl)phenyl; X = Cl, Br) have been converted to the corresponding organometallic reagents.In the absence of 1 the alkyllithium reagents formed react with the solvent, resulting in reduced yields and often alternative products.In the case of the preparation of the arylmetal reagents the presence of 1 suppresses either subsequent orthometalation (R = p-methoxyphenyl) or Wittig rearrangement (R = o-(methoxymethyl)phenyl) to give a clean replacement of halogen by the metal.The presence of THF is also tolerated in the preparation of these two arylmetal reagents by halogen-metal exchange using n-butyllithium in the presence of 1 whereas if 1 is absent little or none of the desired product is obtained.
- Screttas, Constantinos G.,Steele, Barry R.
-
p. 1013 - 1017
(2007/10/02)
-
- MESOMORPHOGENS. VI. CHOLESTERYL AND THIOCHOLESTERYL ESTERS OF CYCLOALKANECARBOXYLIC ACIDS
-
The acylation of cholesterol and thiocholesterol by acid chlorides of ω-cycloalkane carboxylic acid gave the cholesteryl and thiocholesteryl esters of the corresponding acids.The mesogenic capacity of the ω-cycloalkanoates of cholesterol and thiocholesterol is largely a factor of the polarizability of these molecules and not their spatial configuration.A decrease in the geometric anisotropy and concurrent increase in polarizability impart instability to the meso phase of most ω-cycloalkanoates.
- Bogatskii, A. V.,Kondrat'eva, R. V.,Galatina, A. I.,Novikova, N. S.
-
p. 1286 - 1290
(2007/10/02)
-
- LITHIATED CYCLOPROPANONE KETALS
-
The ketene acetal I reacted with dibromocarbene yielding the dibromocyclopropanone ketal II, which was reduced to the monobromide III by treatment with tri-n-butyltin hydride.Reaction of III with n-butyllithium at -78 degC yielded the lithiated cyclopropanone ketal IV, which yielded adducts with acetone, cyclohexanone, cyclohexenone, 3,3,3-trimethoxybutan-2-one, and 3-pentanone.
- Dowd, Paul,Kaufman, Christopher,Kaufman, Paul,Paik, Yi Hyon
-
p. 2279 - 2282
(2007/10/02)
-