50-53-3Relevant academic research and scientific papers
Spatially Resolved Spectroelectrochemical Examination of the Oxidation of Dopamine by Chlorpromazine Cation Radical
Deputy, Andrew,Wu, Huan-Ping,McCreery, Richard L.
, p. 3620 - 3624 (1990)
Spatially resolved absorption measurements of electrogenerated chlorpromazine cation radical (CPZ.+) were used to monitor the kinetics of the homogeneous oxidation of dopamine (DA) in the solution near planar and cylindrical electrodes.Complete concentration vs distance profiles for CPZ.+ were obtained for both planar and convergent diffusion and were used to determine the reaction mechanism and rate constants.The oxidation of DA by CPZ.+ to dopamine orthoquinone involves successive one-electron transfers, and the results are inconsistent with disproportionation of the DA semiquinone.The observed kinetics and rate-limiting step were dependent on the position within the diffusion layer.Near the electrode surface the rate law is first order in CPZ.* and DA, and a second-order rate constant of 2.1 x 105 M-1s-1 was obtained.Further away from the electrode the reaction is second order in CPZ.+ due to the involvement of the second step, and several kinetic parameters for the second electron transfer were obtained.A change in diffusion geometry which occurs at a microwire electrode further perturbs local concentration distributions, and the reaction reaches equilibrium under certain conditions.In all cases, the observed rate laws were consistent with a general expression for the stepwise electron transfer.This report represents the first application of spatially resolved spectroelectrochemistry to a kinetic system and provides unprecedented detail about the CPZ.+/DA reaction.
Halogenated Alkylperoxyl Radicals as Oxidants: Effects of Solvents and of Substituents on Rates of Electron Transfer
Alfassi, Zeev B.,Mosseri, S.,Neta, P.
, p. 3383 - 3385 (1987)
The peroxyl radicals CCl3O2., CHCl2O2., CH2ClO2., CCl3CCl2O2., CFCl2O2., CH3CCl2O2., CF3CHClO2., and CBr3O2. were produced by pulse radiolysis of aerated solutions of the appropriate halogen compound in 2-propanol or 2-propanol-water solutions.Rate constants for one-electron oxidation of chloropromazine by these radicals were determined by kinetic spectrophotometry in various solvent mixtures.The second-order rate constants were found to vary from 1 * 105 to 1 * 109 M-1 s-1.They depend very strongly on the solvent polarity and a reasonable correlation is obtained between log k for a certain peroxyl radical and the dielectric constant of the solvent mixture.The rate constants in the same solvent are strongly dependent of the substituents on the methylperoxyl radical and give a good correlation with the polar substituent constants ?*.
One-Pot Tandem Access to Phenothiazine Derivatives from Acetanilide and 2-Bromothiophenol via Rhodium-Catalyzed C-H Thiolation and Copper-Catalyzed C-N Amination
Rui, Xiyan,Wang, Chao,Si, Dongjuan,Hui, Xuechao,Li, Keting,Wen, Hongmei,Li, Wei,Liu, Jian
, p. 6622 - 6632 (2021/05/29)
A one-pot and step economic reaction involving Rh(III)-catalyzed C-H thiolation and relay Cu(II)-catalyzed C-N amination of acetanilide and 2-bromothiophenol is reported here, with several valuable phenothiazine products obtained. This synthesis protocol proceeds from easily starting materials, demonstrating high atom economy, broad substrate scope, and good yield. Furthermore, the directing group can be easily eliminated, and chlorpromazine is provided in a large scale; thus this synthesis protocol could be utilized to construct phenothiazine scaffolds.
A Focused Library of Psychotropic Analogues with Neuroprotective and Neuroregenerative Potential
Uliassi, Elisa,Pena-Altamira, Luis Emiliano,Morales, Aixa V.,Massenzio, Francesca,Petralla, Sabrina,Rossi, Michele,Roberti, Marinella,Martinez Gonzalez, Loreto,Martinez, Ana,Monti, Barbara,Bolognesi, Maria Laura
, p. 279 - 294 (2018/10/20)
Overcoming the lack of effective treatments and the continuous clinical trial failures in neurodegenerative drug discovery might require a shift from the prevailing paradigm targeting pathogenesis to the one targeting simultaneously neuroprotection and neuroregeneration. In the studies reported herein, we sought to identify small molecules that might exert neuroprotective and neuroregenerative potential as tools against neurodegenerative diseases. In doing so, we started from the reported neuroprotective/neuroregenerative mechanisms of psychotropic drugs featuring a tricyclic alkylamine scaffold. Thus, we designed a focused-chemical library of 36 entries aimed at exploring the structural requirements for efficient neuroprotective/neuroregenerative cellular activity, without the manifestation of toxicity. To this aim, we developed a synthetic protocol, which overcame the limited applicability of previously reported procedures. Next, we evaluated the synthesized compounds through a phenotypic screening pipeline, based on primary neuronal systems. Phenothiazine 2Bc showed improved neuroregenerative and neuroprotective properties with respect to reference drug desipramine (2Aa). Importantly, we have also shown that 2Bc outperformed currently available drugs in cell models of Alzheimer's and Parkinson's diseases and attenuates microglial activation by reducing iNOS expression.
The design and synthesis of an antibacterial phenothiazine-siderophore conjugate
Tarapdar, Abed,Norris, James K.S.,Sampson, Oliver,Mukamolova, Galina,Hodgkinson, James T.
supporting information, p. 2646 - 2650 (2018/11/03)
Siderophore-antibiotic conjugates consist of an antibiotic covalently linked by a tether to a siderophore. Such conjugates can demonstrate enhanced uptake and internalisation to the bacterial cell resulting in significantly reduced MIC values and extended spectrum of activity. Phenothiazines are a class of small molecules that have been identified as a potential treatment for multidrug resistant tuberculosis and latent TB. Herein we report the design and synthesis of the first phenothiazine-siderophore conjugate. A convergent synthetic route was developed whereby the functionalised phenothiazine component was prepared in four steps and the siderophore component also prepared in four steps. In M. smegmatis the functionalised phenothiazine demonstrated an equipotent MIC value in direct comparison to the parent phenothiazine from which it was derived. The final conjugate was synthesised by amide bond formation between the two components and global deprotection of the PMB protecting groups to unmask the catechol iron chelating groups of the siderophore. The synthesis is readily amenable to the preparation of analogues whereby the siderophore component of the conjugate can be modified. The route will be used to prepare a library of siderophore-phenothiazine conjugates for full biological evaluation of much needed new antibacterial agents.
A mechanistic study on the disproportionation and oxidative degradation of phenothiazine derivatives by manganese(III) complexes in phosphate acidic media
Wisniewska, Joanna,Rzesnicki, Pawel,Topolski, Adrian
scheme or table, p. 767 - 774 (2012/07/01)
The oxidative degradation of phenothiazine derivatives (PTZ) by manganese(III) was studied in the presence of a large excess of manganese(III)-pyrophosphate (P2O7 2-), phosphate (PO4 3-), and H+ ions using UV-vis. spectroscopy. The first irreversible step is a fast reaction between phenothiazine and manganese pyrophosphate leading to the complete conversion to a stable phenothiazine radical. In the second step, the cation radical is oxidized by manganese to a dication, which subsequently hydrolyzes to phenothiazine 5-oxide. The reaction rate is controlled by the coordination and stability of manganese(III) ion influenced by the reduction potential of these ions and their strong ability to oxidize many reducing agents. The cation radical might also be transformed to the final product in another competing reaction. The final product, phenothiazine 5-oxide, is also formed via a disproportionation reaction. The kinetics of the second step of the oxidative degradation could be studied in acidic phosphate media due to the large difference in the rates of the first and further processes. Linear dependences of the pseudo-first-order rate constants (k obs) on [Mn III] with a significant non-zero intercept were established for the degradation of phenothiazine radicals. The rate is dependent on [H+] and independent of [PTZ] within the excess concentration range of the manganese(III) complexes used in the isolation method. The kinetics of the disproportionation of the phenothiazine radical have been studied independently from the further oxidative degradation process in acidic sulphate media. The rate is inversely dependent on [PTZ+.], dependent on [H+], and increases slightly with decreasing H+ concentration. Mechanistic consequences of all these results are discussed.
Assembly of substituted phenothiazines by a sequentially controlled CuI/L-proline-catalyzed cascade C-S and C-N bond formation
Dawei, Ma.,Geng, Qian,Zhang, Hui,Jiang, Yongwen
supporting information; experimental part, p. 1291 - 1294 (2010/05/17)
(Chemical equation presented) In the pro-line of fire: A general and efficient cascade reaction approach to substituted phenothiazines, which relies on controlled sequential Cul/L-prolinecatalyzed C-S and C-N bond formations, is described. DMSO = dimethylsulfoxide.
Palladium-catalyzed three-component approach to promazine with formation of one carbon-sulfur and two carbon-nitrogen bonds
Dahl, Troels,Tornoe, Christian W.,Bang-Andersen, Benny,Nielsen, Poul,Jorgensen, Morten
supporting information; scheme or table, p. 1726 - 1728 (2009/02/06)
(Chemical Presented) Zip it up! The use of a Pd/dppf catalyst gives access to the tricyclic phenothiazine scaffold starting from 1-bromo-2-iodobenzenes, aliphatic or aromatic amines, and 2-bromothiophenols in a single reaction flask (see scheme; dppf=1,1′-bis(diphenylphosphanyl) ferrocene; dba=dibenzylidineacetone). This transformation involves thioether formation and subsequent intermolecular and intramolecular aryl amination reactions. The reaction occurs in good overall yield and selectivity.
Heterocyclic compounds
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, (2008/06/13)
A compound of formula (I): STR1 in which X, n, B and Y are as defined in the description. useful as cytokine inhibitors.
Radiolytic Reductions and Oxidations in Dimethyl Sulfoxide Solutions. Solvent Effects on Reactivity of Halogen Atom Complexes
Kumar, M.,Neta, P.
, p. 3350 - 3354 (2007/10/02)
Radiolysis of dimethyl sulfoxide (DMSO) solutions containing various additives was used to achieve clean one-electron reduction or oxidation of solutes.Pulse radiolysis of benzoquinone in DMSO solutions containing acetone and triethylamine permitted conversion of all primary radicals into reducing species.The total yield of reduction in the γ-radiolysis of methyl viologen solutions was found to be 0.37 μmol/J.In the pulse radiolysis of TMPD and triphenylamine in aerated DMSO containing LiCl and/or CCl4, all the primary radicals were converted into oxidizing species and gave a maximum yield of 0.39 μmol/J.In the latter systems, oxidation was partly by halogen atom complexes.The reactivity of complexes of DMSO (DMSO*Cl, DMSO*Br) and of halide ions (Br2.1-, I2.1-) was examined for several organic compounds.DMSO*Cl oxidizes chlorpromazine, triphenylamine, and zinc porphyrin with rate constants of the order of 1E7-1E8 M-1 s-1, and the rates increase upon addition of CH2Cl2 as well as upon addition of water and formamide.DMSO*Cl also reacts with olefins by addition of Cl to the double bond; the rate constants increase upon increasing the electron-donating properties of the substituents on the double bond.The rate constants for oxidation of chlorpromazine by Br2.1- and I2.1- increase by more than 2 orders of magnitude upon changing the solvent from DMSO gradually to water.The change was less with acetonitrile/water mixtures, and the difference is probably due to differences in ion solvation.
