- Reactivity of isothiazolones and isothiazolone-1-oxides in the inhibition of the PCAF histone acetyltransferase
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Development of small molecule inhibitors of the histone acetyltransferase p300/CBP associated factor (PCAF) is relevant for oncology. The inhibition of the enzyme PCAF and proliferation of the cancer cell line HEP G2 by a series of 5-chloroisothiazolones was compared to a series of 5-chloroisothiazolone-1-oxides. The PCAF inhibitory potency of 5-chloroisothiazolones and 5-chloroisothiazolone-1-oxides is influenced by substitution in the 4-position. A study on the reactivity of the HAT inhibitors towards thiols and thiolates indicates that 5-chloroisothiazolones reacted quickly with propane-1-thiolate to provide many products, whereas 5-chloroisothiazolone-1-oxides provide only one defined product. Growth inhibition studies indicate that 5-chloroisothiazolones inhibit proliferation of HEP G2 cells at concentrations between 8.6 and 24 μM, whereas 5-chloroisothiazolone-1-oxides required higher concentrations or showed no inhibition.
- Ghizzoni, Massimo,Haisma, Hidde J.,Dekker, Frank J.
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Read Online
- Green method for synthesizing high value-added mercaptoacid by catalyzing addition reaction of H2S and olefine acid by using ionic liquid as catalyst
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The invention relates to a green method integrating catalysis, reaction and separation, which is used for producing beta-mercapto carboxylic acid through addition of alpha, beta-unsaturated carboxylic acid and H2S by taking amino-functionalized hydrophobic ionic liquid as a catalyst. H2S is activated through tertiary amine alkaline sites contained in the ionic liquid, so that H2S and double bonds of alpha, beta-unsaturated carboxylic acid are subjected to an addition reaction, and recycling of H2S is realized. The product obtained after the reaction can be subjected to water phase liquid-liquid extraction to realize separation of the catalyst and the product, and the ionic liquid can be recycled. In the system, the ionic liquid is both a catalytic medium and a reaction medium, no other organic solvent participates in the system, H2S is efficiently utilized, meanwhile, high-added-value products such as mercapto acid are obtained, and the method is more economical and environmentally friendly and conforms to the development concept of green chemical industry.
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Paragraph 0041; 0055-0056; 0058-0059
(2021/05/05)
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- Synthesis of macrocyclic and medium-sized ring thiolactonesviathe ring expansion of lactams
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A side chain insertion method for the ring expansion of lactams into macrocyclic thiolactones is reported, that can also be incorporated into Successive Ring Expansion (SuRE) sequences. The reactions are less thermodynamically favourable than the analogous lactam- and lactone-forming ring expansion processes (with this notion supported by DFT data), but nonetheless, three complementary protecting group strategies have been developed to enable this challenging transformation to be achieved.
- Palate, Kleopas Y.,Epton, Ryan G.,Whitwood, Adrian C.,Lynam, Jason M.,Unsworth, William P.
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supporting information
p. 1404 - 1411
(2021/02/27)
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- Preparation method of 3-acetylthio-2-methylpropionic acid
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The invention discloses a preparation method of 3-acetylthio-2-methyl propionic acid. The preparation method comprises the following steps: carrying out a reaction on a compound (methacrylic acid) represented by a formula I and hydrogen halide to obtain a compound represented by a formula II, carrying out a reaction on the compound represented by the formula II and sodium hydrosulfide or sodium sulfide to obtain a compound represented by a formula III, and performing an acetylation reaction to obtain a compound represented by a formula IV (3-acetylthio-2-methylpropionic acid). The process forsynthesizing the 3-acetylthio-2-methyl propionic acid has the advantages of being low in cost, easy and convenient to operate, good in yield, environmentally friendly and suitable for industrial production.
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Paragraph 0045-0054; 0064-0066; 0070-0075
(2020/05/02)
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- Method for preparing 2,4-dimethyltetrahydrothiophene-3-one
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The invention relates to a method for preparing 2,4-dimethyltetrahydrothiophene-3-one. The method comprises the following steps: preparing an intermediate 3-mercaptoisobutyric acid from an initial raw material methacrylic acid by adopting thiourea as a mercapto group donor; preparing an intermediate 2,5-dimethyl-3-thiaadipic acid from the intermediate 3-mercaptoisobutyric acid and 2-halogenopropionic acid under the action of an alkali; and preparing 2,4-dimethyltetrahydrothiophene-3-one from the intermediate 2,5-dimethyl-3-thiaadipic acid under the action of a diluent and a metal catalyst. The method for preparing the intermediate 2,5-dimethyl-3-thiaadipic acid from the initial raw material methacrylic acid with low price has the advantages of simple steps, high yield, high product purity, small amount of three wastes in the production process, and industrial production facilitation.
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Paragraph 0030; 0032; 0033
(2017/07/21)
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- Preparation method of sulfhydryl compound
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The invention belongs to the technical field of preparation of sulfur-containing compounds, and relates to a preparation method of a sulfhydryl compound. The sulfhydryl compound is prepared through taking an acrylic acid type compound as a raw material and taking a high-polarity compound as a solvent and introducing H2S gas to react under normal pressure in the presence of a catalyst and an auxiliary agent. The preparation method of the sulfhydryl compound has the advantages of moderate reaction conditions, rapid reaction speed, high conversion ratio and high selectivity, and industrial application is easy to realize.
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Paragraph 0033; 0034
(2017/08/27)
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- SN2-type nucleophilic opening of β-thiolactones (thietan-2-ones) as a source of thioacids for coupling reactions
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β-Thiolactones monosubstituted in the 3-position by alkyl and carbamoyl groups undergo nucleophilic ring opening by arenethiolates through a process involving an SN2-type attack at the 4-position leading to 3-arylthiopropionates substituted in the 2-position. These thiocarboxylates can be trapped in situ by Mukaiyama's reagent or Sanger's reagent through a nucleophilic aromatic substitution process leading to highly activated thioesters that are then allowed to react further with primary or secondary amines leading, overall, to one-pot, three-component syntheses of 3-arylthiopropionamides carrying various substituents in the 2-position. Alternatively, the trapping combination of an electron deficient aryl halide and an amine may be replaced by a 2,4-dinitrobenzenesulfonamide, resulting in the formation of the same products overall with the incorporation of the latent amine in the sulfonamide into the final amide product. In another embodiment, the thiocarboxylate intermediate is allowed to react with a sulfonyl azide, resulting overall in N-arenesulfonyl 3-arylthiopropionamide derivatives.
- Crich, David,Sana, Kasinath
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scheme or table
p. 3389 - 3393
(2009/10/02)
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- METHOD OF PRODUCING β-MERCAPTOCARBOXYLIC ACIDS
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The invention relates to a method for efficiently producing β-mercaptocarboxylic acids using a solid acid catalyst such as zeolite, which product corresponds to respective starting materials selected from α, β-unsaturated carboxylic acids (α, β-unsaturated carboxylic acid, a, β-unsaturated carboxylic acid ester, ex, β-unsaturated amide, a, β-unsaturated aldehide and α, β-unsaturated ketone) and hydrogen sulfides (hydrogen sulfide, sulfide salt and hydrosulfide salt), wherein a solvent compatible with water is used in the reaction. According to the invention, β-mercaptocarboxylic acids which are useful as additives in synthetic materials for pharmaceutical or agricultural agents and in polymer compounds can be industrially produced efficiently by using easily available a, β-unsaturated carboxylic acid (such as crotonic acid) at high yield.
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Page/Page column 31-32
(2009/04/25)
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- Downfield chemical shifts at α-protons and carbons of β-propiothiolactones
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Both the α-protons and carbons of β-propiothiolactones exhibit atypical downfield chemical shifts. The α-protons of β-propiothiolactones with no heteroatom at the α-position appear at 3.53-5.35ppm, whereas the α-carbons appear at 56.9-86.2 ppm. The major cause of the unexpected deshielding effect was rationalized by assuming a through-space interaction between the occupied orbital of the α-carbon and the vacant orbital of sulfur. Copyright
- Lee, Hee Bong,Park, Hyung-Yeon,Lee, Bon-Su,Kim, Young Gyu
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p. 468 - 471
(2007/10/03)
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- SATURATED HYDROXYALKYLQUINOLINE ACIDS AS LEUKOTRIENE ANTAGONISTS
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Compounds having the formula I: STR1 are leukotriene antagonists and inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection.
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- Thiopyrano[2,3,4-cd]indoles as 5-lipoxygenase inhibitors: Synthesis, biological profile, and resolution of 2-[2-[1-(4-chlorobenzyl)-4-methyl-6- [(5-phenylpyridin-2-yl)methoxy]-4,5-dihydro-1H-thiopyrano[2,3,4-cd]indol-2- yl]ethoxy]butanoic acid
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Leukotriene biosynthesis inhibitors have potential as new therapies for asthma and inflammatory diseases. The recently disclosed thiopyrano[2,3,4- cd]indole class of 5-lipoxygenase (5-LO) inhibitors has been investigated with particular emphasis on the side chain bearing the acidic functionality. The SAR studies have shown that the inclusion of a heteroatom (O or S) in conjunction with an α-ethyl substituted acid leads to inhibitors of improved potency. The most potent inhibitor prepared contains a 2-ethoxybutanoic acid side chain. This compound, 14d (2-[2-[1-(4-chlorobenzyl)-4-methyl-6-[(5- phenylpyridin-2-yl)methoxy]-4,5-dihydro-1H-thiopyrano[2,3,4-cd]indol-2- yl]ethoxy]butanoic acid, L-699,333), inhibits 5-HPETE production by human 5- LO and LTB4 biosynthesis by human PMN leukocytes and human whole blood (IC50s of 22 nM, 7 nM and 3.8 μM, respectively). The racemic acid 14d has been shown to be functionally active in a rat pleurisy model (inhibition of LTB4, ED50 = 0.65 mg/kg, 6 h pretreatment) and in the hyperreactive rat model of antigen-induced dyspnea (50% inhibition at 2 and 4 h pretreatment; 0.5 mg/kg po). In addition, 14d shows excellent functional activity against antigen-induced bronchoconstriction in the conscious squirrel monkey [89% inhibition of the increase in R(L) and 68% inhibition in the decrease in C(dyn) (0.1 mg/kg, n = 3)] and in the conscious sheep models of asthma (iv infusion at 2.5 μg/kg/min). Acid 14d is highly selective as an inhibitor of 5-LO activity when compared to the inhibition of human 15-LO, porcine 12-LO and ram seminal vesicle cyclooxygenase (IC50 > 5 μM) or competition in a FLAP binding assay (IC50 > 10 μM). Resolution of 14d affords 14g, the most potent diastereomer, which inhibits the 5-HPETE production of human 5-LO and LTB4 biosynthesis of human PMN leukocytes and human whole blood with IC50s of 8 nM, 4 nM, and 1 μM respectively. The in vitro and in vivo profile of 14d is comparable to that of MK-0591, which has showed biochemical efficacy in inhibiting ex vivo LTB4 biosynthesis and urinary LTE4 excretion in clinical trials.
- Hutchinson,Riendeau,Brideau,Chan,Falgueyret,Guay,Jones,Lepine,Macdonald,McFarlane,Piechuta,Scheigetz,Tagari,Therien,Girard
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p. 1153 - 1164
(2007/10/02)
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- Thiopyrano[2,3,4-c,d]indoles as inhibitors of leukotriene biosynthesis
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Compounds having the formula I: STR1 are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, psoriasis, uveitis and allograft rejection and in preventing the formation of atherosclerotic plaques.
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- Diarylstrylquinoline diacids and pharmaceutical compositions thereof
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Compounds having the formula: STR1 are leukotriene antagonists and inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents.
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- Organotin-containing composition for the stabilization of polymers of vinyl chloride
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An organotin-containing composition for the stabilization of polymers or copolymers of vinyl chloride in which there is incorporated a stabilizing amount of an organotin compound containing at least two tin atoms and which is a mercapto, hydroxy or alkoxy substituted ester of a mercapto acid substituted organotin mercapto acid diester.
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- Process for preparation of an optically active β-mercaptoalkanoic acid
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A process is disclosed wherein an optically active β-mercaptoalkanoic acid represented by formula (I): STR1 wherein R1 is lower alkyl having from 1 to 4 carbon atoms, is prepared by (1) reacting an optically active β-hydroxyalkanoic acid represented by formula (II): STR2 wherein R1 is the same as defined above, with a halogenating reagent to prepare an optically active β-haloalkanoyl halide represented by formula (III): STR3 wherein X is halogen and R1 is the same as defined above; (2) reacting the β-haloalkanoyl halide with water or an aqueous alkaline solution to prepare an optically active β-haloalkanoic acid represented by formula (IV): STR4 wherein X and R1 are each the same as defined above, or a salt thereof, respectively; and (3) reacting the β-haloalkanoic acid or the salt thereof with a reagent capable of converting the halogen into the thiol group, the configuration of the compound (II), (III), and (IV) being retained throughout the process to prepare the compound represented by formula (I). The product of the present invention is useful as an intermediate for preparation of an antihypertensive agent such as N-(3-mercapto-2-D-methylpropanoyl)-L-proline.
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- A Novel Method for the Preparation of Thioformates and Thiols by using Thioformimidates
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Several new S-alkylated thioformimidates were synthesized and their applications to the synthesis of thiolformates and thiols were investigated.Keywords - thioformimidates; thiols; thiolformates; thioformanilide; Michel-type addition
- Matsubara, Yoshio,Nakamura, Toshiyuki,Yoshihara, Masakuni,Maeshima, Toshihishi
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p. 3389 - 3391
(2007/10/02)
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