- Stepwise benzylic oxygenation via uranyl-photocatalysis
-
Stepwise oxygenation at the benzylic position (1°, 2°, 3°) of aromatic molecules was comprehensively established under ambient conditions via uranyl photocatalysis to produce carboxylic acids, ketones, and alcohols, respectively. The accuracy of the stepwise oxygenation was ensured by the tunability of catalytic activity in uranyl photocatalysis, which was adjusted by solvents and additives demonstrated through Stern–Volmer analysis. Hydrogen atom transfer between the benzylic position and the uranyl catalyst facilitated oxygenation, further confirmed by kinetic studies. Considerably improved efficiency of flow operation demonstrated the potential for industrial synthetic application.
- Hu, Deqing,Jiang, Xuefeng
-
supporting information
p. 124 - 129
(2022/01/19)
-
- Palladium-Aminopyridine Catalyzed C?H Oxygenation: Probing the Nature of Metal Based Oxidant
-
A mechanistic study of direct selective oxidation of benzylic C(sp3)?H groups with peracetic acid, catalyzed by palladium complexes with tripodal amino-tris(pyriylmethyl) ligands, is presented. The oxidation of arylalkanes having secondary and tertiary benzylic C?H groups, predominantly yields, depending on the substrate and conditions, either the corresponding ketones or alcohols. One of the three 2-pyriylmethyl moieties, which is pending in the starting catalyst, apparently, facilitates the active species formation and takes part in stabilization of the high-valent Pd center in the active species, occupying the axial coordination site of palladium. The catalytic, as well as isotopic labeling experiments, in combination with ESI-MS data and DFT calculations, point out palladium oxyl species as possible catalytically active sites, operating essentially via C?H abstraction/oxygen rebound pathway. For the ketones formation, O?H abstraction/в-scission mechanism has been proposed.
- Lubov, Dmitry P.,Bryliakova, Anna A.,Samsonenko, Denis G.,Sheven, Dmitriy G.,Talsi, Evgenii P.,Bryliakov, Konstantin P.
-
p. 5109 - 5120
(2021/11/10)
-
- To Rebound or...Rebound? Evidence for the "alternative Rebound" mechanism in Ca'H Oxidations by the systems nonheme Mn Complex/H2O2/carboxylic acid
-
In this work, it has been shown that aliphatic Ca'H oxidations by bioinspired catalyst systems Mn aminopyridine complex/H2O2/carboxylic acid in acetonitrile afford predominantly a mixture of the corresponding alcohol and the ester. The alcohol/ester ratio is higher for catalysts bearing electron-donating groups at the aminopyridine core. Isotopic labeling studies witness that the oxygen atom of the alcohol originates from the H2O2molecule, while the ester oxygen comes exclusively from the acid. Oxidation of ethylbenzene in the presence of acetic acid affords enantiomerically enriched 1-phenylethanol and 1-phenyl acetate, with close enantioselectivities and the same sign of absolute chirality. Experimental data and density functional theory calculations provide evidence in favor of the rate-limiting benzylic H atom abstraction by the high-spin (S = 1) [LMnV(O)OAc]2+active species followed by competitive OH/OC(O)R rebound. This mechanism has been unprecedented for Ca'H oxidations catalyzed by bioinspired Mn complexes. The trends governing the alcohol/ester ratios have been rationalized in terms of steric properties of the catalyst, acid, and substrate. copy; 2021 American Chemical Society.
- Ottenbacher, Roman V.,Bryliakova, Anna A.,Shashkov, Mikhail V.,Talsi, Evgenii P.,Bryliakov, Konstantin P.
-
p. 5517 - 5524
(2021/05/31)
-
- Efficient and selective oxidation of tertiary benzylic C[sbnd]H bonds with O2 catalyzed by metalloporphyrins under mild and solvent-free conditions
-
The direct and efficient oxidation of tertiary benzylic C[sbnd]H bonds to alcohols with O2 was accomplished in the presence of metalloporphyrins as catalysts under solvent-free and additive-free conditions. Based on effective inhibition on the unselective autoxidation and deep oxidation, systematical investigation on the effects of porphyrin ligands and metal centers, and apparent kinetics study, the oxidation system employing porphyrin manganese(II) (T(2,3,6-triCl)PPMn) with bulkier substituents as catalyst, was regarded as the most promising and efficient one. For the typical substrate, the conversion of cumene could reach up to 57.6% with the selectivity of 70.5% toward alcohol, both of them being higher than the current documents under similar conditions. The superiority of T(2,3,6-triCl)PPMn was mainly attributed to its bulkier substituent groups preventing metalloporphyrins from oxidative degradation, its planar structure favoring the interaction between central metal with reactants, and the high efficiency of Mn(II) in the catalytic transformation of hydroperoxides to alcohols.
- Hu, Meng-Yun,Liu, Lei,Qi, Bei,She, Yuan-Bin,Shen, Hai-Min,Ye, Hong-Liang
-
-
- Method for synthesizing tertiary alcohol by catalytically oxidizing benzyl tertiary C-H bonds of aromatic hydrocarbon through metalloporphyrin
-
The invention discloses a method for synthesizing tertiary alcohol by catalytically oxidizing benzyl tertiary C-H bonds of aromatic hydrocarbon through metalloporphyrin. The method comprises the following steps: dispersing metalloporphyrin (1*10-1%, mol/mol) into aromatic hydrocarbon; sealing the reaction system, heating to 40-120 DEG C while stirring, introducing an oxidant (0.10-1.0 MPa), keeping the set temperature and pressure, carrying out reactions for 3.0-24.0 hours under stirring, and carrying out after-treatment on the reaction solution to obtain the product aromatic benzyl tertiary alcohol. The method has the advantages of shortest conversion path, highest atom economy, lower reaction temperature, lower environmental influence and the like, and the selectivity of aromatic benzyl tertiary alcohol is high. In addition, the content of aromatic hydrocarbon hydroperoxide is low, and the safety coefficient is high. The invention provides an efficient, feasible and safe method for synthesizing aromatic benzyl tertiary alcohol through selective catalytic oxidation of benzyl tertiary C-H bonds of aromatic hydrocarbon.
- -
-
Paragraph 0062-0063
(2020/09/30)
-
- Isopropanol as a hydrogen source for single atom cobalt-catalyzed Wacker-type oxidation
-
The first example of a heterogeneous cobalt catalytic system for Wacker-type oxidation catalyzed by a single atom dispersed Co-N/C catalyst using alcohol as the hydrogen source under an oxygen atmosphere is presented. By combining a well-designed, controlled experiment and various methods of characterization, we determined that single atom cobalt was the active center rather than nanoparticle or oxide counterparts.
- An, Yue,Chen, Bo,Gao, Shuang,Huang, Guanwang,Luo, Huihui,Shang, Sensen,Wang, Lianyue
-
p. 2769 - 2773
(2020/06/17)
-
- Deoxyfluorination with CuF2: Enabled by Using a Lewis Base Activating Group
-
Deoxyfluorination is a primary method for the formation of C?F bonds. Bespoke reagents are commonly used because of issues associated with the low reactivity of metal fluorides. Reported here is the development of a simple strategy for deoxyfluorination, using first-row transition-metal fluorides, and it overcomes these limitations. Using CuF2 as an exemplar, activation of an O-alkylisourea adduct, formed in situ, allows effective nucleophilic fluoride transfer to a range of primary and secondary alcohols. Spectroscopic investigations have been used to probe the origin of the enhanced reactivity of CuF2. The utility of the process in enabling 18F-radiolabeling is also presented.
- Bode, Bela E.,Chabbra, Sonia,Champion, Sue,Dawson, Daniel M.,Sood, D. Eilidh,Sutherland, Andrew,Watson, Allan J. B.
-
supporting information
p. 8460 - 8463
(2020/04/10)
-
- Method for selectively oxidizing cumene compounds
-
The invention relates to a method for selectively oxidizing cumene compounds, and the method comprises the following steps: placing cumene compounds shown in a formula (I), an iron porphyrin catalyst,an oxidant and a dispersant into a ball milling tank, sealing the ball milling tank, performing ball milling for 3 to 24 hours at a rotating speed of 100 to 800 rpm at room temperature, stopping ballmilling once every 1 to 3 hours in the ball milling process, discharging gases in the ball milling tank, finishing the reaction, and performing post-treatment on a reaction mixture to obtain product2-phenyl-2-propanol compound shown in a formula (II); according to the invention, the oxidation conversion of the cumene and derivatives thereof is realized through solid-phase ball milling, the reaction mode is novel, the operation is convenient, and the energy consumption is low; the method needs no organic solvent, thus effectively avoiding the use of toxic and harmful organic solvents and being green and environment-friendly; has low peroxide content and high safety factor, and high 2-phenyl-2-propanol and derivative selectivity and meets the social requirements of the current green chemical process, environmental compatibility chemical process and biological compatibility chemical process.
- -
-
Paragraph 0109; 0110
(2019/11/21)
-
- Hindered dialkyl ether synthesis with electrogenerated carbocations
-
Hindered ethers are of high value for various applications; however, they remain an underexplored area of chemical space because they are difficult to synthesize via conventional reactions1,2. Such motifs are highly coveted in medicinal chemistry, because extensive substitution about the ether bond prevents unwanted metabolic processes that can lead to rapid degradation in vivo. Here we report a simple route towards the synthesis of hindered ethers, in which electrochemical oxidation is used to liberate high-energy carbocations from simple carboxylic acids. These reactive carbocation intermediates, which are generated with low electrochemical potentials, capture an alcohol donor under non-acidic conditions; this enables the formation of a range of ethers (more than 80 have been prepared here) that would otherwise be difficult to access. The carbocations can also be intercepted by simple nucleophiles, leading to the formation of hindered alcohols and even alkyl fluorides. This method was evaluated for its ability to circumvent the synthetic bottlenecks encountered in the preparation of 12 chemical scaffolds, leading to higher yields of the required products, in addition to substantial reductions in the number of steps and the amount of labour required to prepare them. The use of molecular probes and the results of kinetic studies support the proposed mechanism and the role of additives under the conditions examined. The reaction manifold that we report here demonstrates the power of electrochemistry to access highly reactive intermediates under mild conditions and, in turn, the substantial improvements in efficiency that can be achieved with these otherwise-inaccessible intermediates.
- Xiang, Jinbao,Shang, Ming,Kawamata, Yu,Lundberg, Helena,Reisberg, Solomon H.,Chen, Miao,Mykhailiuk, Pavel,Beutner, Gregory,Collins, Michael R.,Davies, Alyn,Del Bel, Matthew,Gallego, Gary M.,Spangler, Jillian E.,Starr, Jeremy,Yang, Shouliang,Blackmond, Donna G.,Baran, Phil S.
-
p. 398 - 402
(2019/11/05)
-
- COMPOUNDS AND THEIR METHODS OF USE
-
The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including Dravet syndrome or epilepsy are also provided herein.
- -
-
Page/Page column 140-141
(2018/06/12)
-
- COMPOSITIONS USEFUL FOR TREATING DISORDERS RELATED TO KIT
-
Compounds and compositions useful for treating disorders related to Kit are described herein.
- -
-
Paragraph 0164-0166
(2016/04/26)
-
- SUBSTITUTED PYRROLOPYRDINES AS INHIBITORS OF BROMODOMAIN
-
The present invention relates to compounds of formula (I) and to salts thereof, wherein R1, R2, and Q have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of bromodomains. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various bromodomain-mediated disorders.
- -
-
Page/Page column 126; 127
(2016/06/06)
-
- SUBSTITUTED PYRROLOPYRIDINES AS INHIBITORS OF BROMODOMAIN
-
The present invention relates to compounds of formula (I) and to salts thereof, wherein R1, R2, and Q have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of bromodomains. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various bromodomain-mediated disorders.
- -
-
Page/Page column 86; 87
(2016/06/13)
-
- Mechanism of Selective C-H Hydroxylation Mediated by Manganese Aminopyridine Enzyme Models
-
The mechanism of selective oxidation of aliphatic C-H groups with H2O2 in the presence of aminopyridine Mn complexes, modeling the reactivities of natural oxygenases of the cytochrome P450 superfamily, has been examined. The oxygenation of C-H groups proceeds via hydrogen atom abstraction by the electrophilic metal site; the logarithm of C-H oxidation rates correlates linearly with bond dissociation energies for homolytic C-H bond cleavage. Hammett correlations and stereospecificity studies reflect the formation of a short-lived electron-deficient radical intermediate. Isotopic labeling studies confirm the incorporation of 18O from added H218O, thus providing so far lacking evidence for the oxomanganese(V)-mediated oxidation mechanism. (Figure Presented).
- Ottenbacher, Roman V.,Talsi, Evgenii P.,Bryliakov, Konstantin P.
-
-
- IMIDE AND ACYLUREA DERIVATIVES AS MODULATORS OF THE GLUCOCORTICOID RECEPTOR
-
Novel non-steroidal compounds are provided which are useful in treating diseases or disorders associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-KB activity, including metabolic and inflammatory and immune diseases or disorders, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a pharmaceutically-acceptable salt thereof, in which the variables are as defined in the specification.
- -
-
Page/Page column 67; 68; 81; 82
(2015/03/13)
-
- GLUCOSYLCERAMIDE SYNTHASE INHIBITORS FOR THE TREATMENT OF DISEASES
-
Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or conditions associated with the enzyme glucosylceramide synthase (GCS).
- -
-
Paragraph 0001243
(2015/04/15)
-
- Discovery of Mammalian Target of Rapamycin (mTOR) Kinase Inhibitor CC-223
-
We report here the synthesis and structure-activity relationship (SAR) of a novel series of mammalian target of rapamycin (mTOR) kinase inhibitors. A series of 4,6- or 1,7-disubstituted-3,4-dihydropyrazino[2,3-b]pyrazine-2(1H)-ones were optimized for in v
- Mortensen, Deborah S.,Perrin-Ninkovic, Sophie M.,Shevlin, Graziella,Zhao, Jingjing,Packard, Garrick,Bahmanyar, Sogole,Correa, Matthew,Elsner, Jan,Harris, Roy,Lee, Branden G. S.,Papa, Patrick,Parnes, Jason S.,Riggs, Jennifer R.,Sapienza, John,Tehrani, Lida,Whitefield, Brandon,Apuy, Julius,Bisonette, René R.,Gamez, James C.,Hickman, Matt,Khambatta, Godrej,Leisten, Jim,Peng, Sophie X.,Richardson, Samantha J.,Cathers, Brian E.,Canan, Stacie S.,Moghaddam, Mehran F.,Raymon, Heather K.,Worland, Peter,Narla, Rama Krishna,Fultz, Kimberly E.,Sankar, Sabita
-
p. 5323 - 5333
(2015/08/03)
-
- C-S bond cleavage in aromatic sulfide radical cations
-
The results of our recent studies of the structural effects on the C-S bond fragmentation process of aromatic sulfur radical cations are reported.
- Lanzalunga, Osvaldo
-
p. 322 - 330
(2013/07/25)
-
- Structure and C-S bond cleavage in aryl 1-methyl-1-arylethyl sulfide radical cations
-
Steady state and laser flash photolysis (LFP) of a series of p-X-cumyl phenyl sulfides (4-X-C6H4C(CH3) 2SC6H5: 1, X = Br; 2, X = H; 3, X = CH 3; 4, X = OCH3) and p-X-cumyl p-methoxyphenyl sulfides (4-X-C6H4C(CH3)2SC6H 4OCH3: 5, X = H; 6, X = CH3; 7, X = OCH 3) has been carried out in the presence of N-methoxy phenanthridinium hexafluorophosphate (MeOP+PF6-) under nitrogen in MeCN. Steady state photolysis showed the formation of products deriving from the C-S bond cleavage in the radical cations 1+?-7 +? (2-aryl-2-propanols and diaryl disulfides). Formation of 1+?-7+? was also demonstrated by LFP experiments evidencing the absorption bands of the radical cations 1+?- 3+? (λmax = 530 nm) and 5+?- 7+? (λmax = 570 nm) mainly localized in the arylsulfenyl group and radical cation 4+? (λ max = 410, 700 nm) probably mainly localized in the cumyl ring. The radical cations decayed by first-order kinetics with a process attributable to the C-S bond cleavage. On the basis of DFT calculations it has been suggested that the conformations most suitable for C-S bond cleavage in 1 +?-4+? and 7+? are characterized by having the C-S bond almost collinear with the π system of the cumyl ring and by a significant charge and spin delocalization from the ArS ring to the cumyl ring. Such a delocalization is probably at the origin of the observation that the rates of C-S bond cleavage result in very little sensitivity to changes in the C-S bond dissociation free energy (BDFE). A quite large reorganization energy value (λ = 43.7 kcal mol-1) has been calculated for the C-S bond scission reaction in the radical cation. This value is much larger than that (λ = 12 kcal mol-1) found for the C-C bond cleavage in bicumyl radical cations, a reaction that also leads to cumyl carbocations.
- Baciocchi, Enrico,Bettoni, Marta,Del Giacco, Tiziana,Lanzalunga, Osvaldo,Mazzonna, Marco,Mencarelli, Paolo
-
supporting information; scheme or table
p. 573 - 582
(2011/03/19)
-
- 4-AMINO-5-OXO-7, 8-DIHYDROPYRIMIDO [5,4-F] [1,4] OXAZEPIN-6 (5H) -YL) PHENYL DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
-
The invention provides compounds of Formula (I), wherein R1, R2a, R2b, R3, m and A are as defined herein, as well as compositions thereof and methods for treating a disease, condition or disorder that is modulated by the inhibition of the diacylglycerol O-acyltransferase 1 (DGAT-1) enzyme by administering the compounds of the present invention and/or compositions thereof.
- -
-
Page/Page column 56
(2010/08/09)
-
- (3-oxo)pyridazin-4-ylurea derivatives as PDE4 inhibitors
-
New (3-oxo)pyridazin-4-ylurea derivatives having the chemcial structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of the phosphodiesterase IV (PDE4).
- -
-
Page/Page column 38
(2010/07/03)
-
- SUBSTITUTED DIAZEPINE SULFONAMIDES AS BOMBESIN RECEPTOR SUBTYPE-3 MODULATORS
-
Certain novel substituted diazepine sulfonamides are ligands of the human bombesin receptor and, in particular, are selective ligands of the human bombesin receptor subtype-3 (BRS-3). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the modulation of BRS-3, such as obesity, and diabetes.
- -
-
Page/Page column 41
(2010/11/03)
-
- INHIBITORS OF AKT ACTIVITY
-
The instant invention provides for compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity by administering the compound to a patient in need of treatment of cancer.
- -
-
Page/Page column 73
(2010/08/09)
-
- The discovery of MK-0674, an orally bioavailable cathepsin K inhibitor
-
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
-
scheme or table
p. 887 - 892
(2010/08/22)
-
- MTOR KINASE INHIBITORS FOR ONCOLOGY INDICATIONS AND DISEASES ASSOCIATED WITH THE MTOR/P13K/AKT PATHWAY
-
Provided herein are Heteroaryl Compounds having the following structure: R2 N (I) or (II) wherein R1 -R4 are as defined herein, compositions comprising an effective amount of a Heteroaryl Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, neurodegenerative diseases, diabetes, obesity, neurological disorders, age-related diseases, or cardiovascular conditions, comprising administering an effective amount of a Heteroaryl Compound to a patient in need thereof.
- -
-
Page/Page column 92
(2010/06/17)
-
- VITAMIN D-LIKE COMPOUND
-
The present invention provides a compound represented by the following general formula (I): or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing such a compound, and the like. The compound or a pharmaceutically acceptable
- -
-
Page/Page column 42
(2008/06/13)
-
- Further studies with the 2-amino-1,3-thiazol-4(5H)-one class of 11β-hydroxysteroid dehydrogenase type 1 inhibitors: Reducing pregnane X receptor activity and exploring activity in a monkey pharmacodynamic model
-
A series of compounds containing the 2-amino-1,3-thiazol-4(5H)-one core were found to be potent inhibitors of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). One of our lead compounds from this series activated the human nuclear xenobiotic
- Fotsch, Christopher,Bartberger, Michael D.,Bercot, Eric A.,Chen, Michelle,Cupples, Rod,Emery, Maury,Fretland, Jenne,Guram, Anil,Hale, Clarence,Han, Nianhe,Hickman, Dean,Hungate, Randall W.,Hayashi, Michael,Komorowski, Renee,Liu, Qingyian,Matsumoto, Guy,St. Jean Jr., David J.,Ursu, Stefania,Véniant, Murielle,Xu, Guifen,Ye, Qiuping,Yuan, Chester,Zhang, Jiandong,Zhang, Xiping,Tu, Hua,Wang, Minghan
-
experimental part
p. 7953 - 7967
(2009/12/07)
-
- The ritter reaction under truly catalytic bronsted acid conditions
-
Simple organic acids like 2,4-dinitrobenzenesulfonic acid (DNBSA) catalyze the Ritter reaction of secondary benzylic alcohols giving rise to the corresponding N-benzylacetamides in usually high yields. Reactions can be conducted without exclusion of oxygen and without the need of dry solvents. With tertiary α,α-dimethylbenzylic alcohols a different pathway involving a formal dimerization reaction takes place under the acid-catalytic conditions used. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Sanz, Roberto,Martinez, Alberto,Guilarte, Veronica,Alvarez-Gutierrez, Julia M.,Rodriguez, Felix
-
p. 4642 - 4645
(2008/03/12)
-
- Synthesis and SAR of novel 2-arylthiazolidinones as selective analgesic N-type calcium channel blockers
-
A series of new N-type (Cav2.2) calcium channel blockers derived from the 'hit' structures 2-(3-bromo-4-fluorophenyl)-3-(2-pyridin-2-ylethyl)thiazolidin-4-one 9 and its 2-[4-(4-bromophenyl)pyridin-3-yl]-3-isobutyl analogue 10 is described. Exte
- Knutsen, Lars J.S.,Hobbs, Christopher J.,Earnshaw, Christopher G.,Fiumana, Andrea,Gilbert, Jenny,Mellor, Sarah L.,Radford, Fleur,Smith, Nichola J.,Birch, Philip J.,Russell Burley,Ward, Stuart D.C.,James, Iain F.
-
p. 662 - 667
(2007/10/03)
-
- Kinetics and mechanism of acid catalysed hydration of α- methylstyrenes
-
Twelve para-substituted α-methylstyrenes with substituents H, CH 3, CF3, CH3O, CH3S, F, Cl, Br, CH3CO, CH3SO2, CN a NO2 were synthesised; additionally, the acid catalysed hydration kinetics of these compounds were measured in sulfuric acid in a concentration range c from 0.017 to 9.58 mol l-1, at 25.0°C. The observed rate constants obtained were used to construct the kinetic acidity function and calculate the catalytic rate constants. Based on the evaluation of the acidity function kinetic dependence on acid medium concentration, and the substituent effects of acid catalysed hydration of α-methylstyrenes on the catalytic rate constants, the mechanism of acid catalysed hydration was verified. The mechanism involves the addition of a proton to the double bond of α-methylstyrene in the rate-limiting reaction step denoted as A-SE2. No evident difference was found between the effects of the acid medium on the acid catalysed hydration of styrenes and α-methylstyrenes, which indicates very similar activity coefficients of the reactants, and of the transition state of both substrates. The substituent effects evaluation shows that the rate-limiting step of the reaction consists in the addition of a proton to the substrate. The carbocation formation in the transition state of this reaction step proceeds roughly half-way compared with the extent of the carbocation formation by cumyl chloride hydrolysis. The obtained carbocation is in particular stabilised by the substituents with +M effect, while the influence of the substituents with -M and I effects is significantly smaller.
- Pytela, Oldrich,Trlida, Bronislav
-
p. 1025 - 1036
(2008/09/19)
-
- 11C-LABELED BENZYL-LACTAM COMPOUNDS AND THEIR USE AS IMAGING AGENTS
-
The invention relates to ""C-labeled compounds, their preparation, compositions comprising an effective amount of a ""C-labeled compound, and the use of a ""C-labeled compound as a radiopharmaceutical for positron emission tomography.
- -
-
Page/Page column 21-22
(2008/06/13)
-
- INHIBITORS OF AKT ACTIVITY
-
The instant invention provides for compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms. The invention also provides for compositions comprising such inhibitory compounds and method
- -
-
Page/Page column 43
(2008/06/13)
-
- Pyridyl piperazines for the treatment of CNS disorders
-
This invention is directed to compounds of Formula I and to pharmaceutical compositions comprising the compound of Formula I. where the dashed line represents an optional double bond; and where n is 1 or 2, and Ar1, Ar2, . . . and Z
- -
-
Page/Page column 14
(2010/02/15)
-
- PIPERAZINYLPHENALKYL LACTAM/AMINE LIGANDS FOR THE 5HT1B RECEPTOR
-
The present invention relates to novel derivatives, that are compounds of Formula (I), wherein R1, R2, R3, R14, X, Y, n and m are defined herein, their pharmaceutically acceptable salts, pharmaceutical compositions and methods using said compounds in treating or preventing depression, anxiety, obsessive compulsive disorder (OCD) and other disorders for which selective antagonists, inverse agonists and partial agonists of serotonin 1 (5-HT1) receptors, specifically, antagonists of 5-HT1B are useful.
- -
-
Page/Page column 81-82
(2010/11/30)
-
- PYRIDIL-LACTAMS AND THEIR USE 5 -HTl RECEPTORS LIGAN
-
The present invention relates to novel pyridyl-lactams, compounds of the formula (I), wherein R1 is a group of the formula G1, G2, G3 or G4 depicted below, and R3, Y, R6, R7, R8, R13, a, n and m are as defined herein, their pharmaceutically acceptable salts, pharmaceutical compositions, their preparation and intermediates therefrom, and their use in treating or preventing depression, anxiety, obsessive compulsive disorder (OCD) and other disorders for which a 5-HT1B antagonist is indicated.
- -
-
Page/Page column 34-35
(2010/11/24)
-
- REVERSIBLE INHIBITORS OF MONOAMINE OXIDASE A AND B
-
The instant invention relates to compounds of formula I, diagrammed below, wherein R3, E, D and Y are defined in the application, which are useful as reversible inhibitors of monoamine oxidase-B and/or monoamine oxidase-A, and therefore useful to treat or prevent neurological diseases or conditions in mammals, preferably humans.
- -
-
Page/Page column 42
(2008/06/13)
-
- NOVEL BENZYL(IDENE)-LACTAM DERIVATIVES
-
The present invention relates to novel benzyl(idene)-lactam derivatives, compounds of the formula (I) wherein R1 is a group of the formula G1 or G2 depicted below, wherein R1, R3, R6, R13, X, a, n and m are as defined herein, their pharmaceutically acceptable salts, and pharmaceutical compositions which include selective antagonists, inverse agonists and partial agonists of serotonin 1 (5-HT1) receptors, specifically, of one or both of the 5-HT1A and 5-HT1B receptors. The compounds of the invention are useful in treating or preventing depression, anxiety, obsessive compulsive disorder (OCD) and other disorders for which a 5-HT1 agonist or antagonist is indicated and have reduced potential for cardiac side effects, in particular QTc prolongation.
- -
-
Page/Page column 35
(2008/06/13)
-
- ARALKYL AND ARALKYLIDENE HETEROCYCLIC LACTAMS AND IMIDES
-
The present invention relates to compounds of the formula (I) wherein R1, R2, R3, X, Y and the dashed line are defined in the specification, to intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use as psychotherapeutic agents.
- -
-
Page/Page column 54-55
(2008/06/13)
-
- Photooxidation of aryl alkanes by a decatungstate/triethylsilane system in the presence of molecular oxygen
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Decatungstate photocatalyzes the oxidation of aryl alkanes to the corresponding tertiary hydroperoxides and alcohols, in the presence of molecular oxygen. The addition of triethylsilane to the reaction mixture substantially increases the proportion of hydroperoxide formed.
- Lykakis, Ioannis N.,Orfanopoulos, Michael
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p. 7645 - 7649
(2007/10/03)
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- Indium(III) bromide-catalyzed chemioselective dimerization of vinylarenes
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Indium(III) bromide catalyzes the dimerization of α-substituted vinylarenes. Chemioselectivity towards open chain or cyclic dimers depends on the nature of the substituent at the aryl group of the vinylarene.
- Peppe, Clovis,Lang, Ernesto Schulz,De Andrade, Fabiano Molinos,De Castro, Liérson Borges
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p. 1723 - 1726
(2007/10/03)
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- Discovery of L-791,943: a potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor.
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Structure-activity relationship studies directed toward improving the potency and metabolic stability of CDP-840 (3) resulted in the discovery of L-791,943 (11n) as a potent (HWB TNF-alpha = 0.67 microM) and orally active phosphodiesterase type 4 (PDE4) inhibitor. This compound, which bears a stable bis-difluoromethoxy catechol and a pendant hexafluorocarbinol, exhibited a long half-life in rat and in squirrel monkey. It is well tolerated in ferret with an emetic threshold greater than 30 mg/kg (po) and was found to be active in the ovalbumin-induced bronchoconstriction model in guinea pig and in the ascaris-induced bronchoconstriction models in sheep and squirrel monkey.
- Guay, Daniel,Hamel, Pierre,Blouin, Marc,Brideau, Christine,Chan, Chi Chung,Chauret, Nathalie,Ducharme, Yves,Huang, Zheng,Girard, Mario,Jones, Tom R,Laliberte, France,Masson, Paul,McAuliffe, Malia,Piechuta, Hanna,Silva, Jose,Young, Robert N,Girard, Yves
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p. 1457 - 1461
(2007/10/03)
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- Vilsmeier-Haack reaction of tertiary alcohols: Formation of functionalised pyridines and naphthyridines
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Vilsmeier-Haack reaction of 2-arylpropan-2-ols proceeds with multiple iminoalkylations leading to the formation of conjugated iminium salts which on ammonium acetate-induced cyclisation afford 4-arylnicotinaldehydes in good yields. Tertiary alcohols derived from aliphatic or alicyclic ketones by the addition of methyl Grignard are converted into substituted pyridines and naphthyridines by the action of Vilsmeier's reagent in N,N-dimethylformamide followed by nucleophile-assisted cyclisation in the presence of ammonium acetate.
- Thomas,Asokan
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p. 2583 - 2587
(2007/10/03)
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- Metal cation-exchanged montmorillonite(Mn+-mont)-catalysed carbonyl-ene reactions
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Metal cation-exchanged montmorillonite (Mn+-mont) works in acetonitrile at 80°C as a Lewis acid catalyst for the intermolecular carbonyl-ene reaction of α-methylstyrenes with paraformaldehyde to give the corresponding homoallylic alcohols, Zr4+-mont being the most effective of the many Mn+-mont catalysts examined. Similarly, the catalyst is also useful for the highly stereoselective intramolecular cyclization of citronellals to afford isopulegols, the reaction being much faster. Regeneration of the catalyst is confirmed for Zr4+-mont, which can be effectively recycled at least five times.
- Tateiwa, Jun-Ichi,Kimura, Akihiro,Takasuka, Masaaki,Uemura, Sakae
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p. 2169 - 2174
(2007/10/03)
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- Conformational effects on retinoid receptor selectivity. 2. Effects of retinoid bridging group on retinoid X receptor activity and selectivity
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The natural retinoid 9-cis-retinoic acid is an activating ligand for both the retinoic acid receptors (BARs) and the retinoid X receptors (RXRs), which are members of the retinoid/thyroid hormone/steroid hormone family of nuclear receptor proteins that activate gene transcription through specific response elements. The pharmacophoric groups necessary to confer RXR selectivity were established by evaluating the ability of 21 conformationally restricted retinoids to activate the TREpal retinoic acid receptor response element for gene transcription in the presence of one of the three PAR subtypes or RXRα. In contrast to those retinoids selective for the RARs, these RXR-selective retinoids have one less atom in the bridge linking the hydrophobic and carboxylic acid termini of the retinoid skeleton. Therefore, a one-carbon bridge replaces the 19-methyl group and 9E-double bond of 9-cis-retinoic acid and is further functionalized by inclusion in an isopropylidene group, a dioxolane ring, or a cyclopropane ring for optimal RXRα activity and selectivity. In addition, the β-geranylidene and 20-methyl-(11E,13E)- dienoic acid groups of 9-cis-retinoic acid are replaced by a 5,6,7,8- tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl ring and a 4-carboxylphenyl ring, respectively, for optimal activation and selectivity. RXRα selectivity is reduced on replacement of the 4-carboxylphenyl group by a 2-carboxyl-5- thienyl group or the 9-cis-retinoic acid methylpentadienoic acid terminus.
- Dawson,Jong,Hobbs,Cameron,Chao,Pfahl,Lee -,Shroot,Pfahl
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p. 3368 - 3383
(2007/10/03)
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- Electronic Effects on Triplet and Singlet Excited-State Carbonyl Formation in the Thermolysis 3-Aryl-3-methyl-1,2-dioxetanes
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A series of para- and meta-substituted 3-aryl-3-methyl-1,2-dioxetanes (1) was studied in order to evaluate the electronic effect of substituents on the efficiencies of excited-state carbonyl production.All substituents reduced the efficiency of triplet carbonyl production.Several correlations point to the formation of a triplet carbonyl exciplex, originating from a triplet biradical, in the thermolysis of 1.It also appears that substituent variation in the proacetophenone portion of 1 results in triplet efficiency changes primarily in formaldehyde, which can be rationalized in terms of a triplet exciplex.Substituent effects on singlet (S1) efficiency are markedly different from those observed with triplet efficiencies.The possibility of heavy-atom effects in 1 was pursued with p-Br and m-Br substituents.No detectable heavy-atom effect was observed with singlet (S1) efficiencies, but the p-Br substituent appeared to decrease the triplet efficiency.This suggests that a p-Br heavy-atom effect may operate from the triplet exciplex, providing the approximations used in the evaluations of the heavy-atom effect are valid.The effect of substituents on rate of thermolysis of 1 provides further evidence for a biradical mechanism.
- Richardson, William H.,Stiggal-Estberg, Diana L.
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p. 4173 - 4179
(2007/10/02)
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- Novel Ketones from Roman Camomile Oil
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β-Damascenone (1) has been identified in the fraction of Roman camomile (Anthemis nobilis) oil that contains homologues of carvotanacetone. 5-(3-Furyl)-2-methyl-1-penten-3-one (2), (E)-1-(2,6-dimethylphenyl)-2-buten-1-one (8), 4-isopropenylbenzaldehyde (4
- Thomas, Alan F.,Egger, Jean-Claude
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p. 2393 - 2396
(2007/10/02)
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- HALOGEN-CONTAINING ALKYL AROMATIC PEROXIDES
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New halogen-containing peroxides were obtained by alkylation of saturated, acetylenic, and vinylacetylenic hydroperoxides with p-halogen-containing alkyl aromatic alcohols in an acetic acid medium in the presence of catalytic amounts of perchloric acid.
- Vilenskaya, M. R.,Petrovskaya, G. A.,Pokhmurskaya, M. V.
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p. 841 - 843
(2007/10/02)
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