- Rational design of fluorescent probes for targeted: In vivo nitroreductase visualization
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Nitroreductase (NTR) has been recognized as a biomarker for identifying the hypoxic status of cancers. Therefore, it is of high scientific interest to design effective fluorescent probes for tracking NTR activity. However, studies on elucidation of the structure-performance relationship of fluorescent probes and those providing valuable insight into optimized probe design have rarely been reported. Three BODIPY based fluorescent probes were made by conjugation of para-, ortho-, and meta-nitrobenzene to the BODIPY core via a thiolether bond, respectively. Our study revealed that the linkage and nitro substituent position significantly influence the capability of nitroreductase detection.
- Chen, Ji-An,Gao, Jie,Gu, Xianfeng,Li, Mimi,Tan, Jiahui,Yin, Xiaofan,Zhao, Zhen
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supporting information
p. 4744 - 4747
(2020/07/13)
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- Janus head type lone pair-π-lone pair and S?F?S interactions in retaining hexafluorobenzene
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A series of eight tris-arylthiotriazines were synthesized to study the lone pair-π interaction between the triazine ring centroid of these molecules and halogenated solvents. All the eight compounds were characterized using 1H and 13C NMR spectroscopy and single crystal X-ray diffraction techniques. All these compounds show interesting structural properties in the solid state. Unprecedented Janus head type lp?π?lp and S?F?S interactions were observed between one of the tris-arylthiotriazines and hexafluorobenzene.
- Mehrotra, Sonam,Angamuthu, Raja
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p. 4438 - 4444
(2016/07/06)
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- No-carrier-added [18F]fluoroarenes from the radiofluorination of diaryl sulfoxides
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No-carrier-added [18F]fluoroarenes were synthesized through the radiofluorination of diaryl sulfoxides with [18F]fluoride ion. Diaryl sulfoxides bearing a para electron-withdrawing substituent readily gave the corresponding 4-[18F]fluoroarenes in high RCYs. This process broadens the scope for preparing novel 18F-labeling synthons and PET radiotracers.
- Chun, Joong-Hyun,Morse, Cheryl L.,Chin, Frederick T.,Pike, Victor W.
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supporting information
p. 2151 - 2153
(2013/03/14)
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- Catalytic transfer hydrogenation of aryl sulfo compounds
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A new method to reduce aryl sulfo compounds via transfer hydrogenation was investigated, using Pd/C as a catalyst, and 2-propanol or formic acid as hydrogen sources. This new process is simple and clean.
- Chen, Xinzhi,Zhou, Shaodong,Qian, Chao
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experimental part
p. 179 - 185
(2012/05/21)
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- A simple, fast and chemoselective method for the preparation of arylthiols
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An efficient and convenient method for the synthesis of arylthiols by reaction of sulfonyl chlorides with triphenylphosphine in toluene is reported.
- Bellale, Eknath V.,Chaudhari, Mahesh K.,Akamanchi, Krishnacharya G.
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experimental part
p. 3211 - 3213
(2010/03/01)
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- A general and efficient approach to aryl thiols: Cul-catalyzed coupling of aryl iodides with sulfur and subsequent reduction
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A Cul-catalyzed coupling reaction of aryl iodides and sulfur powder takes place in the presence of K2CO3 at 90 °C. The coupling mixture is directly treated with NaBH4 or triphenylphosphine to afford aryl thiols in good to
- Jiang, Yongwen,Qin, Yuxia,Xie, Siwei,Zhang, Xiaojing,Dong, Jinhua,Ma, Dawei
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supporting information; scheme or table
p. 5250 - 5253
(2009/12/28)
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- Thermodynamic study of σH complexes in nucleophilic aromatic substitution reactions: Relative stabilities of electrochemically generated radicals
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The mechanism for the electrochemical oxidation of σH complexes, such as 1-hydro-1-alkoxy/sulfoxy or -fluoro-2,4-dinitro/2,4,6- trinitrocyclohexadienyl anions, has been widely studied by means of cyclic voltammetry and controlled-potential electrolysis. Previous studies have shown that the electrochemical oxidation of σH complexes, formed by the addition of carbon or nitrogen nucleophiles followed by a two electron mechanism, corresponding to the formal elimination of the hydride anion (nucleophilic aromatic substitution of hydrogen mechanism, the NASH mechanism). For these σH complexes (Nu- = OH-, -OR, -SR, -F), the electrochemical reaction takes place by a one-electron mechanism and is followed by the radical elimination of the leaving group with the consequent recovery of the starting material. This mechanism is similar to that proposed for the electrochemical oxidation of σX complexes (nucleophilic aromatic substitution of a heteroatom, the NASX mechanism). The operating mechanism in each case, the NASH or NASX, can be rationalized in terms of thermodynamics. The standard potentials of the σ complex and/or the leaving group as well as the bond dissociation energies (BDEs) are determinant factors. This study has not led to a significant improvement in the electrochemical preparation of aromatic-substituted compounds, but does help to understand and predict the usefulness or uselessness of using the nucleophilic aromatic substitution route to obtain a desired product. Finally, the current approach extends the electrochemical methodology to different chemical fields, for example, to general nondestructive methods for the detection, identification, and quantification of either organic pollutants or explosives in different solvents. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Gallardo, Iluminada,Guirado, Gonzalo
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scheme or table
p. 2463 - 2472
(2009/04/06)
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- N-alkylthio beta-lactams, alkyl-coenzyme a asymmetric disulfides, and aryl-alkyl disulfides as anti-bacterial agents
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The present invention provides N-alkylthio β-lactams and disulfide compounds (e.g., alkyl-coenzyme A asymmetric disulfides or aryl-alkyl disulfides), compositions containing such compounds, and method of their use as anti-bacterial agents.
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Page/Page column 9
(2008/12/07)
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- Unsymmetric aryl-alkyl disulfide growth inhibitors of methicillin-resistant Staphylococcus aureus and Bacillus anthracis
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This study describes the antibacterial properties of synthetically produced mixed aryl-alkyl disulfide compounds as a means to control the growth of Staphylococcus aureus and Bacillus anthracis. Some of these compounds exerted strong in vitro bioactivity. Our results indicate that among the 12 different aryl substituents examined, nitrophenyl derivatives provide the strongest antibiotic activities. This may be the result of electronic activation of the arylthio moiety as a leaving group for nucleophilic attack on the disulfide bond. Small alkyl residues on the other sulfur provide the best activity as well, which for different bacteria appears to be somewhat dependent on the nature of the alkyl moiety. The mechanism of action of these lipophilic disulfides is likely similar to that of previously reported N-thiolated β-lactams, which have been shown to produce alkyl-CoA disulfides through a thiol-disulfide exchange within the cytoplasm, ultimately inhibiting type II fatty acid synthesis. However, the mixed alkyl-CoA disulfides themselves show no antibacterial activity, presumably due to the inability of the highly polar compounds to cross the bacterial cell membrane. These structurally simple disulfides have been found to inhibit β-ketoacyl-acyl carrier protein synthase III, or FabH, a key enzyme in type II fatty acid biosynthesis, and thus may serve as new leads to the development of effective antibacterials for MRSA and anthrax infections.
- Turos, Edward,Revell, Kevin D.,Ramaraju, Praveen,Gergeres, Danielle A.,Greenhalgh, Kerriann,Young, Ashley,Sathyanarayan, Nalini,Dickey, Sonja,Lim, Daniel,Alhamadsheh, Mamoun M.,Reynolds, Kevin
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p. 6501 - 6508
(2008/12/21)
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- Sulfoximine-pyrimidine Macrocycles and the salts thereof, a process for making them, and their pharmaceutical use against cancer
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The invention relates to macrocyclic sulfoximines according to the general Formula I: wherein A, X, Y, R1, R2 and R3 have the meaning as given in the specification and the claims and the salts thereof; to pharmaceutical co
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Page/Page column 19
(2008/06/13)
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- Benzoazine mono-N-oxides and benzoazine 1,4 dioxides and compositions therefrom for the therapeutic use in cancer treatments
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The present invention relates to a synergetistic composition comprising one or more benzoazine-mono-N-oxides, and one or more benzoazine 1,4 dioxides for use in cancer therapy. The invention also provides a range of novel 1,2,4 benzoazine-mono-N-oxides and related analogues. These can be used as potentiators of the cytotoxicity of existing anticancer drugs and therapies for cancer treatment.
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Page column 24; 46
(2010/02/08)
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- Structure-activity relationships of 1,2,4-benzotriazine 1,4-dioxides as hypoxia-selective analogues of tirapazamine
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Tirapazamine (TPZ, 1,2,4-benzotriazin-3-amine 1,4-dioxide) is a bioreductive hypoxic cytotoxin currently in Phase II/III clinical trials in combination with radiotherapy and with cisplatin-based chemotherapy. As part of a program to develop TPZ analogues with improved solubility/potency and therapeutic indices, we synthesized 34 1,2,4-benzotriazin-3-amine 1,4-dioxides (BTO) to examine structure-activity relationships (SAR) for ring substitution. The electronic, hydrophobic, and steric parameters of substituents at the 5-, 6-, 7-, and 8-positions were systematically varied, and the aqueous solubility and one-electron reduction potentials [E(1)] of the analogues were determined. For each compound, we determined cell killing of mouse SCCVII tumor cells in vitro under aerobic and hypoxic conditions by clonogenic survival and determined their relative hypoxic toxicity (RHT; relative to TPZ) and hypoxic cytotoxicity ratio (HCR). A subset of compounds was independently evaluated using a 96-well SRB proliferation assay, the data from which correlated well with that derived by the clonogenic endpoint. Most substituents, except 5- and 8-dimethylamino and 8-diethylamino, gave analogues less soluble than TPZ. E(1) values ranged from -240 mV through -670 mV (with TPZ having a value of -456 mV) and correlated well with the electronic parameter σ for substituents at the 5-, 6-, 7-, and 8-positions. Aerobic cytotoxic potency showed a strong positive correlation with E(1) (i.e., electron-withdrawing substituents increased aerobic toxicity). Hypoxic cytotoxicity also generally increased with increasing E(1), with a maximum (RHT up to 3.9-fold) seen in halo- and trifluoromethyl-substituted BTO derivatives having E(1) between ca. -370 to -400 mV. Analogues with high HCRs (>50) all had E(1)s in the range -450 to -510 mV (weakly electron-donating substituents) with the exception of the 8-CF3 analogue, which had an HCR of 112 against SCCVII despite a high E(1) of -372 mV). The results suggest that ring-A substituents in BTO analogues can be used to predictably vary one-electron reduction potentials and also provide a much better definition than previously of the optimum range of these reduction potentials for a desirable biological activity profile (high HCR, RHT, and solubility).
- Hay, Michael P.,Gamage, Swarna A.,Kovacs, Mary S.,Pruijn, Frederik B.,Anderson, Robert F.,Patterson, Adam V.,Wilson, William R.,Brown, J. Martin,Denny, William A.
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p. 169 - 182
(2007/10/03)
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- Oxidative cleavage of S-Arylmercaptoacetic acids by pyridinium chlorochromate: Kinetic and correlation analysis
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Kinetics of oxidation of 24 S-Arylmercaptoacetic acids (SAMA) by pyridinium chlorochromate (PCC) have been studied in acid medium. The product of oxidation is the corresponding thiophenol. The rate data of meta- and para-substituted acids have been correlated well with σI, σ°R values and the meta-compounds correlate well with F,R values. The reaction constants are negative and of smaller magnitudes. Further, the ortho-substituted acids show a good correlation with triparametric equation involving Taft's σI and σ°R and charton's steric parameter v. There is no considerable steric contribution to the total orthosubstituent effect. Based on these observations, the mechanism involving the formation of protonated arylsulfinylacetic acid intermediate, followed by an intramolecular rearrangement leading to the product thiophenol has been proposed.
- Kabilan,Girija,Rajagopal
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p. 683 - 688
(2007/10/03)
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- Oxidative Cleavage of S-Arylmercaptoacetic Acids by Sodium Perborate: Kinetic and Correlation Study
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Kinetics of oxidation of twenty six S-arylmercaptoacetic acids (SAMA) (I) by sodium perborate (PB) have been studied in acid medium.The product of oxidation is the corresponding thiophenol.The rate data of meta- and para-substituted acids have been correlated with DSP equations.While the para-compounds correlate well with ?I and ?0R values, the meta-compounds correlate well with ?I and ?-R values.The reaction constants are negative and of smaller magnitudes.Further, the ortho-substituted acids show a good correlation with a triparametric equation involving Taft's ?I and ?0R and Charton's steric parameter ν.There is a considerable steric contribution to the total ortho-substituent effect.Based on these observations, mechanism involving the formation of protonated arylsulfinylacetic acid intermediate, followed by an intramolecular rearrangement leading to the product thiophenol has been proposed.
- Kabilan, S.,Pandiarajan, K.,Krishnasamy, K.,Sankar, P.
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p. 443 - 452
(2007/10/02)
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- The E1cB Mechanism for Thiocarbamate Ester Hydrolysis: Equilibrium and Kinetic Studies
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The alkaline hydrolyses of a series of S-aryl thiocarbamate esters have been measured and the mechanism confirmed to be dissociative.Equilibrium constant for the synthesis of thiocarbamates from thiol and isocyanic acid have been obtained for aqueous media using both kinetic and analytical techniques.Hammett and Broensted parameters for the equilibrium reaction indicate that there is less positive effective charge on the sulphur in the thiocarbamate compared with that on the oxygen in the oxygen analogue.Theoretical arguments are advanced to show that the dissociative reactions of simple carbamate anions involve a planar geometry of the paticipating atoms.
- Bourne, Nicholas,Williams, Andrew,Douglas, Kenneth T.,Penkava, Thomas R.
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p. 1827 - 1832
(2007/10/02)
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- REDUCTION OF SULFONIC ACIDS WITH PHOSPHORUS PENTASULFIDE
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Arene, and alkanesulfonic acids are easily reduced to the corresponding polysulfides R-(S)n-R (n= 2.9 3.3) by treatment with phosphorus pentasulfide.In this reaction, the formation of both P-O-S and P-S-H linkages is considered to be involved in the key step of the reduction.
- Oae, Shigeru,Togo, Hideo
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p. 4701 - 4704
(2007/10/02)
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- An E1cB Mechanism for the Alkaline Hydrolysis of Thiolesters of Fluorene-9-carboxylic Acid: Effect of Ester Conjugate Base Structure on Differential Eliminative Reactivity of Oxygen and Sulphur Nucleofuges
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The alkaline hydrolysis of a series of thiolesters of fluorene-9-carboxylic acid has been studied and pseudo-first-order rate constants, kobs (hydroxide ion in excess), showed saturation with respect to hydroxide ion concentration for any given
- Alborz, Manoochehr,Douglas, Kenneth T.,Said, Fouad M.
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p. 1467 - 1470
(2007/10/02)
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- Leaving Group Effects in Thiolester Hydrolysis. Part 2. On the Possibility of an Elimination-Addition (Keten) Mediated Pathway in S-Acetylcoenzyme A Basic Hydrolysis and Acetyl Transfer
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Alkaline hydrolysis rates (kHO(1-)) at 25 deg C in aqueous solution for a series of S-alkyl and S-aryl thiolacetates, including S-acetylcoenzyme A, were correlated (as their logarithms) with the pKa of the conjugate acid of the thiolate leaving group to give a slope (βl.g.) of -0.33.In comparison with the corresponding oxygen esters, thiolesters are, for the basicity of a given leaving species, one to two orders of magnitude less reactive towards hydroxide ion and show little dispersion into aryl and alkyl leaving groups, ascribed to the lower steric sensitivity of thiolacetate esters compared with the oxygen analogues.The small value of βl.g. and the lower reactivity of S- than O-esters are offered as evidence of a bimolecular associative (BAc2) mechanism for basic hydrolysis.The E2 route is excluded by the lack of deuterium incorporation into the (acetate) product of hydrolysis.In spite of the accepted acidity of thiolacetates, a kinetically insignificant amount of ester conjugate base is formed in aqueous solution even at high, non-physiological pH and thus S-acetylcoenzyme A does not hydrolyse by an E1cB pathway.
- Douglas, Kenneth T.,Yaggi, Norbert F.,Mervis, Cynthia M.
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p. 171 - 174
(2007/10/02)
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