- TARGETED ANTIMICROBIAL PHOTODYNAMIC THERAPY
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The present application relates generally to a method and a composition matter that provides a rapid and potent antimicrobial photodynamic inactivation (aPDI) of pathogenic bacteria that express high-affinity cell-surface hemin receptors (CSHRs) using Ga(III)-protoporphyrins IX (GaPpIX or Ga-PpIX). The invention provides an effective treatment option for infections of skin or body cavities that are accessible to visible-light irradiation, such as a handheld LED array emitting visible light (405 nm), especially for infections caused by Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), pathogenic staphylococci, Streptococcus mutans, S. pneumoniae, S. pyogenes, streptococci, corynebacteria, mycobacteria, and Bacillus anthracis.
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Paragraph 0180
(2019/10/29)
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- Facile iodination of the vinyl groups in protoporphyrin IX dimethyl ester and subsequent transformation of the iodinated moieties
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Iodination of protoporphyrin IX dimethyl ester using phenyliodine bis(trifluoroacetate) (PIFA) and I2 was studied. Iodine added to both the C3- and C8-vinyl groups equally to afford the iodohydrin or iodoether in the presence of water or alcohol, respectively. Any meso-hydrogen atom was not substituted by an iodine atom under these conditions, although both the vinyl group and one of the meso positions of methyl pyropheophorbide-a bearing a chlorin π-system, a chlorophyll-a derivative, was modified with PIFA and I2. The reaction intermediates derived from the porphyrin were more reactive than those from the chlorin and liable to form intermolecular linkages. The obtained 2-iodo-1-hydroxyethyl group was transformed into a formyl group by a mild treatment. The corresponding iodoether moiety was readily converted into the acetyl group under basic conditions. These transformations were also applicable to smaller olefins such as styrene.
- Miyata, Kota,Yasuda, Satoru,Masuya, Takuto,Ito, Satoshi,Kinoshita, Yusuke,Tamiaki, Hitoshi,Oba, Toru
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supporting information
p. 3707 - 3711
(2018/05/28)
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- Process For Preparing Porphyrin Derivatives, Such As Protoporphyrin (IX) And Synthesis Intermediates
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The present invention relates to a process for preparing a porphyrin of formula (I), optionally in the form of a salt with an alkali metal and/or in the form of a metal complex: in which: R and R′ are as defined in claim 1, comprising: a step of condensation, in an acidic medium, between a dipyrromethane of formula (II): in which R′b is as defined above for (I), and a dipyrromethane of formula (III): in which R″ is as defined in claim 1, and also the compounds of formula (III).
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Page/Page column 13; 20
(2008/12/07)
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- Electronic effects of peripheral substituents at porphyrin meso positions
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Porphyrins are stable molecules with a macrocyclic conjugated system and often peripheral substituents. This unique structure makes the electronic properties of the four meso-carbons (the methine bridges) nearly identical. Replacement of the weakly electron-polarizing 2,4-vinyl groups of protoporphyrin IX with strongly electron-polarizing acetyl groups not only leads to much lower meso-carbon reactivities toward electrophilic aromatic substitution but also results in a significant meso-selectivity (the β- and γ-meso- positions become much more nucleophilic (basic) than the α- and δ-meso-positions). To further investigate the relationship between the porphyrin meso-carbon reactivities and the peripheral substituents, two monoacetylporphyrin analogues also were synthesized. This investigation not only leads to empirical rules for predicting porphyrin meso-carbon selectivities but also provides important models for theoretical calculations of porphyrin aromaticity.
- Zhu, Yaoqiu,Silverman, Richard B.
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p. 233 - 239
(2007/10/03)
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- Synthesis of ether- and carbon-linked polycarboranyl porphyrin dimers for cancer therapies
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Porphyrin dimers bearing multiple carborane cages for potential use as sensitizers in boron neutron capture therapy (BNCT) and photodynamic therapy (PDT) were synthesized from protoporphyrin dimethyl ester and characterized. Diastereomeric ether-linked di
- Isaac, Meden F.,Kahl, Stephen B.
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p. 232 - 243
(2007/10/03)
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- Oxidative rearrangement of acetylporphyrins
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Oxidative rearrangement of 2-/4-monoacetyl- and 2,4-diacetlydeuteroporphyrin IX dimethyl esters by methanolic thallic nitrate trihydrate in presence of conc, nitric acid furnished the corresponding mono- and dimethoxycarbonylmethylporphyrins, respectively.
- Chakrabarty, Manas
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p. 761 - 764
(2007/10/03)
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- Synthesis of fluorine analogs of protoporphyrin potentially useful for diagnosis and therapy of cancer. IV. Synthesis of (trifluorovinyl)vinyland (1-chloro-2,2-difluorovinyl)vinyldeuteroporphyrins
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Trifluoro or chlorodifluoro analogs of protoporphyrin, the compounds in the title, were synthesized for use in the diagnosis and therapy of cancer. 3- Or 8-acetyldeuteroporphyrin dimethyl esters (2 and 3) were iodinated with iodine in the presence of potassium carbonate to the corresponding iodo compounds (5 and 6). The iodo compounds (5 and 6) were treated with bis(trifluorovinyl)zinc in the presence of tetrakis(triphenylphosphine)palladium to give trifluorovinyl derivatives (7 and 8) in good yields. Reduction of the acetyl group of 7 and 8 with sodium borohydride afforded the corresponding hydroxyethyl derivatives (9 and 10). Compounds (9 and 10) were dehydrated with methanesulfonyl chloride and triethylamine to give (trifluorovinyl)vinyldeuteroporphyrin dimethyl esters (11 and 12). Treatment of 5 and 6 with bis(1-chloro-2,2-difluorovinyl)zinc in the presence of tetrakis(triphenylphosphine)palladium, followed by similar reactions as above gave (1-chloro-2,2-difluorovinyl)vinyldeuteroporphyrin dimethyl esters (17 and 18).
- Shigeoka, Tsuyoshi,Kuwahara, Yasuhisa,Watanabe, Kiyoko,Sato, Kazuyuki,Omote, Masaaki,Ando, Akira,Kumadaki, Itsumaro
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p. 1326 - 1329
(2007/10/03)
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- Porphyrin Dimers as Photosensitizers in Photodynamic Threapy
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Porphyrin dimers 9 with ether linkages and possible isomers bis-1,3,5,8-tetramethyl-2-vinylporphin-4-yl>ethyl> ether (10) bis-1,3,5,8-tetramethyl-4-vinylporphin-2-yl>ethyl> ether (11), and 1--1,3,5,8-tetramethyl-2-vinylporphin-4-yl>ethyl 1--1,3,5,8-tetramethyl-4-vinylporphin-2-yl>ethyl ether (12) were synthesized from the corresponding (1-hydroxyethyl)vinyldeuteroporphyrin IX dimethyl esters (Hvd).The pure Hvd isomers 2-(1-hydroxyethyl)-4-vinyldeuteroporphyrin IX dimethyl ester (7) and 4-(1-hydroxyethyl)-2-vinyldeuteroporphyrin IX dimethyl ester (8) were obtained from 2-acetyl-4-(1-hydroxyethyl)deuteroporphyrin IX dimethyl ester (3) and 4-acetyl-2-(1-hydroxyethyl)deuteroporphyrin IX dimethyl ester (4).Porphyrins 3 and 4 were prepared either by partial reduction of 2,4-diacetyldeuteroporphyrin IX dimethyl ester (2) or by oxidation of hematoporphyrin IX dimethyl ester (1) by using tetra-n-propylammonium perruthenate (Prn4N)(RuO4) with N-methylmorpholine N-oxide as an oxidizing agent.The in vivo photosensitizing ability and therapeutic ratios of dimers 9-12 were compared with that of Photofrin II in the SMT-F tumor growing subcutaneously in DBA/2 Ha mice.These dimers were found to have better tumorcidal activity than Photofrin II with reduced skin phototoxicity.
- Pandey, Ravindra K.,Smith, Kevin M.,Dougherty, Thomas J.
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p. 2032 - 2038
(2007/10/02)
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- THE SYNTHESIS OF DIHEMATOPORPHYRIN ETHER AND RELATED PORPHYRIN DIMERS
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Dihematoporphyrin ether (DHE) has been synthesised by two separate procedures; these routes also allow the synthesis of ether linked porphyrin dimers containing one or two vinyl groups rather than hydroxyethyl side chains.The latter dimers, but not DHE, have anti-cancer activity.
- Morris, Ian K.,Ward, A. David
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p. 2501 - 2504
(2007/10/02)
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- PARTIAL SYNTHESES OF 1- AND 3-METHYL DEUTERIATED DERIVATIVES OF PROTOPORPHYRIN-IX FROM PROTOHEMIN
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Treatment of 2,4-diacetyldeuteroporphyrin-IX dimethyl ester (3) with sodium methoxide in methanol-d affords the 1,3-di-(trideuteriomethyl) derivative in which the acetyl methyls and propionate methylenes adjacent to the ester carbonyl have also been deuteriated.The acetyl methyls and propionates can be back-exchanged under acidic conditions, but the 1- and 3-methyls retain their isotope labeling.Reduction with sodium borohydride, followed by dehydration affords the corresponding 1,3-di-(trideuteriomethyl)-protoporphyrin-IX dimethyl ester (4) with approximately 95percent deuteriation in the methyls.Insertion of iron and hydrolysis affords the corresponding hemin (15), suitable for n.m.r. studies of reconstituted heme proteins.A similar sequence of reactions with 2- and 4- monoacetyldeuteroporphyrins (5) and (6) gives the 1- and 3-(trideuteriomethyl) derivatives and these are, in turn, further acetylated and transformed into the corresponding mono-trideuteriomethylprotoporphyrins (7) and (8), and hemins (22) and (23).
- Smith, Kevin M.,Leung, Hiu-Kwong,Parish, Daniel W.
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p. 2743 - 2761
(2007/10/02)
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- Manipulation of Vinyl Groups in Protoporphyrin IX: Introduction of Deuterium and Carbon-13 Labels for Spectroscopic Studies
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Using commercially available hemin (5) as the starting material, routes for preparation of monovinyl deuterated (27), monovinyl carbon-13 enriched (41,42), and divinyl carbon-13 enriched (43,44) derivatives of protoporphyrin IX dimethyl ester (1) are described.The monovinyl carbon-13 enriched porphyrins 41 and 42 were obtained by way of a previously reported Wittig reaction on Spirographis and iso-Spirographis porphyrin dimethyl esters 28 and 39, respectively.A new efficient partial synthesis of Spirographis porphyrin dimethyl ester (28) from deuteroporphyrin IX dimethyl ester (7) is reported, and in this the key formyl group at the 2 position is inserted by way of a Vilsmeier reaction employing a hindered amide.
- Smith, Kevin M.,Fujinari, Eugene M.,Langry, Kevin C.,Parish, Daniel W.,Tabba, Hani D.
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p. 6638 - 6646
(2007/10/02)
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- The Chemistry of Pyrrolic Compounds. XLV. Haematoporphyrin Derivative: Haematoporphyrin Diacetate as the Main Product of the Reaction of Haematoporphyrin with a Mixture of Acetic and Sulfuric Acids
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A mixture of acetic and sulfuric acids converts haematoporphyrin into a complex mixture of porphyrins of which the main product has been characterized as the diacetate (1g).Other compounds identified in the reaction mixture were the known vinylporphyrins (1b-d), (1h) and (1i) and the isomeric monoacetoxyethyl(monohydroxyethyl)porphyrins (1l) and (1m).Analysis of the reaction mixture was complicated by the presence of 1'-ethoxyethyl derivatives (1e) or (1f), (1j) and (1k) which presumably arose by solvolysis of the corresponding acetate with ethanol present in the chloroform used for the the chromatographic separation.
- Clezy, Peter S.,Hai, Ton That,Henderson, Robert W.,Thuc, Le van
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p. 585 - 597
(2007/10/02)
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