- The mode of toxic action of the pesticide Gliftor: The metabolism of 1,3-difluoroacetone to (-)-erythro-fluorocitrate
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The biochemical toxicology of 1,3-difluoroacetone, a known metabolite of the major ingredient of the pesticide Gliftor (1,3-difluoro-2-propanol), was investigated in vivo and in vitro. Rat kidney homogenates supplemented with coenzyme A, ATP, oxaloacetate, and Mg2+ converted 1,3-difluoroacetone to (-)-erythro-fluorocitrate in vitro. Administration of 1,3-difluoroacetone (100 mg kg-1 body weight) to rats in vivo resulted in (-)-erythro-fluorocitrate synthesis in the kidney, which was preceded by an elevation in fluoride levels and followed by citrate accumulation. Animals dosed with 1,3-difluoroacetone did not display the 2-3 hour lag phase in either (-)-erythro-fluorocitrate synthesis or in citrate and fluoride accumulation characteristic of animals dosed with 1,3-difluoro-2-propanol. We demonstrate that the conversion of 1,3-difluoro-2-propanol to 1,3-difluoroacetone by an NAD+-dependent oxidation is the rate-limiting step in the synthesis of the toxic product, (-)-erythro-fluorocitrate from 1,3-difluoro-2-propanol. Prior administration of 4-methylpyrazole (90 mg kg-1 body weight) was shown to prevent the conversion of 1,3-difluoro-2-propanol (100 mg kg-1 body weight) to (-)-erythro-fluorocitrate in vivo and to eliminate the fluoride and citrate elevations seen in 1,3-difluoro-2-propanol-intoxicated animals. However, administration of 4-methylpyrazole (90 mg kg-1 body weight) to rats 2 hours prior to 1,3-difluoroacetone (100 mg kg-1 body weight) was ineffective in preventing (-)-erythro-fluorocitrate synthesis and did not diminish fluoride or citrate accumulation in vivo. We conclude that the prophylactic and antidotal properties of 4-methylpyrazole seen in animals treated with 1,3-difluoro-2-propanol derive from its capacity to inhibit the NAD+-dependent oxidation responsible for converting 1,3-difluoro-2-propanol to 1,3-difluoroacetone in the committed step of the toxic pathway.
- Menon,Feldwick,Noakes,Mead
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- REACTIVE EXTRACTION OF WATER
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Described herein are methods and compounds for extracting water from an aqueous solution. For example, some embodiments include method for extracting water from an aqueous solution, comprising contacting the aqueous solution with a compound comprising one or more carbonyl moieties having an equilibrium constant for a hydration of the carbonyl moiety of at least about 0.5; separating a composition comprising the hydrated compound from the aqueous solution; and reacting the hydrated compound to obtain water.
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Paragraph 0077; 0078
(2020/04/09)
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- Small molecule inhibitors of caspases
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The present invention provides compounds having formula (I): and pharmaceutically acceptable derivatives thereof, wherein A, B, D, E, G, J, n, and R1 are as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof as caspase inhibitors and for the treatment of disorders caused by excessive apoptotic activity.
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- Water-soluble trioxanes as potent and safe antimalarial agents
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Biologically-active, water soluble, 3-substituted trioxanes of the formula STR1 wherein R represents a COOH-- substituted aryl group, a substituted or unsubstituted heteroaryl group or an alkyl group, and C12 -(p-carboxy)benzyloxy trioxanes of formula STR2 wherein R represents a substituted or unsubstituted alkyl, alkenyl, aryl or heteroaryl group and methods for their use as antiparasitic agents, particularly for the treatment of malaria.
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- C3 substituted trioxanes useful as antiparasitic drugs
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Novel biologically-active 3-substituted trioxanes of the formula STR1 wherein R represents a substituted alkyl or aryl group of 1-20, preferably 1-12, carbon atoms, and methods for the use of biologically-active 3-substituted trioxanes of this formula as antiparasitic agents, particularly for the treatment of malaria.
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- Stereocontrolled synthesis of fluorosqualenes and fluoroepoxysqualenes as inhibitors of squalene epoxidase and 2,3-oxidosqualene cyclase
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Z-Fluorosqualene derivatives having one or more fluorine atoms at the terminal methyls of the squalene skeleton have been synthesized.A highly stereoselective synthesis, based on a Wittig reaction, was developed together with a new method for obtaining bi
- Ceruti, Maurizio,Amisano, Simona,Milla, Paola,Viola, Franca,Rocco, Flavio,et al.
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p. 889 - 894
(2007/10/02)
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- Synthesis of methyl 2-(fluoromethyl)-3-fluoroalanine
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The title compound 1b, an important intracellular pH indicator, is conveniently prepared in 44% overall yield from 1,3-difluoro-2-propanol (2). Key steps in this synthesis include oxidation of 2 to 1,3-difluoroacetone (3) in near quantitative yield using KMnO4/CuSO4 and the addition of trimethylsilyl cyanide to a phenyl glycinol protected imine. The efficiency of this process was enhanced further by use of crude reaction mixtures of their solutions.
- Davis,Reddy,Bental,Deutsch
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p. 701 - 702
(2007/10/02)
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- Halogenated tetraenyl prostaglandin derivatives
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The present invention relates to a novel class of halogenated tetraenyl prostaglandin compounds represented by the following general formula STR1 or a pharmaceutically acceptable salt thereof, wherein Y is --CH=CH-- or --CH2 --CH2 --; R1 is H or a lower alkyl of 1 to 6 carbons; n is an integer from 0 to 3; m is an integer from 0 to 3 and n+m=3; X is Cl or F provided that when X is Cl, n is 2 and m is 1; R2 and R3 are independently H, lower alkyl from 1 to 6 carbons, Cl, --CH2 Cl, --CH2 F, --CHCl2, --CCl3, or taken together form a cycloalkyl of 3 to 6 carbons; R4 is H, lower alkyl from 1 to 6 carbons, Cl, F or taken together with R3 form a cycloalkenyl of 4 to 6 carbons; and provided that at least one of --CHn Xm, R2, R3 and R4 includes a chlorine or fluorine atom.
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- ANALYSE STRUCTURALE DES HALOGENOPROPANONES
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Methylene bending mode analysis (1400-1500 cm-1 region) and dipole moment determinations are carried out in the dissolved state (solvent CCl4) for fluoropropanone (I) and 1,3-difluoropropanone (II).The results are consistent with the existence of two conformations, "cis" and "trans", for (I) and one conformation "cis-trans" for (II).Theoretical evaluations of conformer stabilities by the PCILO method and Onsager formalism are in reasonable agreement with these experimental results.
- Maury, Catherine,Bonniol, Alain,Lere-Porte, Jean-Pierre,Petrissans, Jean
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p. 217 - 228
(2007/10/02)
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