- Bimane cyclic esters, possible stereologues of trypanothione as antitrypanosomal agents. Bimanes 29
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Tricyclic esters derived from bimanes have been synthesized with ring sizes near or equal to that of trypanothione disulfide (T(S)2), a bis-glutathionylspermidine that is involved in regulating the thiol status of Leishmania and other trypanosomatids. Modest activity for many of the compounds against Leishmania donovani with a maximum at the T(S)2 ring size suggests that the esters act as T(S)2 surrogates. However, no inhibition of T(S)2-reductase is observed for a number of the compounds. A series of tricyclic bimane amides with structures more closely analogous to T(S)2 are inactive in biological tests. New approaches were developed for the synthesis of the amides. The surprising effectiveness of the cyclic ester synthesis is explained. Acid chloride formation catalyzed by sulfides is briefly described.
- Kosower,Radkowsky,Fairlamb,Croft,Neal
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Read Online
- Bifunctional cytotoxic agents
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Cytotoxic dimers comprising CBI-based and/or CPI-based sub-units, antibody drug conjugates comprising such dimers, and to methods for using the same to treat cancer and other conditions.
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Page/Page column 71
(2018/11/02)
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- COPOLYCARBONATE AND METHOD FOR PREPARING THE SAME
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Provided are a copolycarbonate having superior weather resistance as well as excellent mechanical properties, and a preparation method thereof.
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Paragraph 0050-0051
(2017/11/06)
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- Synthesis and monoamine transporter binding properties of 2,3-cyclo analogues of 3β-(4′-aminophenyl)-2β-tropanemethanol
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A series of cyclo-3β-(4-aminophenyl)-2β-tropanemethanol analogues (5a-m) possessing varying linker groups between the 2- and 3-position on the tropane ring were synthesized and evaluated for their monoamine transporter binding properties. The results show that binding to the dopamine and serotonin transporters (DAT and 5-HTT) is highly dependent on the specific linker used. Cyclo-3β-(4-aminophenyl)-2β-tropanemethanol pimelic acid ester/amide (5b) had an IC50 of 3.8 nM at the DAT. Cyclo-3β-(4-aminophenyl)- 2β-tropanemethanol sebacic acid ester/amide (5e) had a Ki of 1.9 nM at the 5-HTT and was 68- and 737-fold selective for the 5-HTT relative to the DAT and NET. Small changes to the size as well as the electrostatic and hydrophobic properties of the 2,3-linker in 5b or 5e led to much less potent analogues at all three transporters. These results suggest that the high affinity for 5b and 5e at the DAT and 5-HTT may be due to their specific conformational properties.
- Carroll, F. Ivy,Blough, Bruce E.,Huang, Xiaodong,Nie, Zhe,Mascarella, S. Wayne,Deschamps, Jeffrey,Navarro, Hernán A.
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p. 4589 - 4594
(2007/10/03)
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- Structure-reactivity studies on .OH radical reaction with substituted dialkyl sulfides
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The results of the reaction of an .OH radical with a number of functionalized organic sulfides reported here demonstrate that the pH, the nature of the functional group and the chain length affect the nature of the .OH radical reaction with sulfides. The transient absorption spectrum (λmax = 295 nm), formed on reaction of .H atoms and .OH radicals with an aqueous solution of 2-(methylthio)ethanol and 2-(ethylthio)ethanol is assigned to the α-thio radical. It decayed by second order kinetics with 2k = 5.2 × 109 dm3 mol-1 s-1 and was quenched by oxygen. The transient absorption spectra (λmax = 480 and 500 nm respectively), obtained on reaction with .OH radicals (pH = 1 ), are assigned to a sulfur centered dimer radical cation. The variation of the transient absorbance with pH showed an inflection point at pH =2.1. The reaction of .OH radicals (pH = 6) with 2,2′-thiodiethanoyl chloride showed the formation of α-thio radicals (λmax = 300 nm) and an OH-adduct (λ = 350-380 nm), whereas in acidic solutions, the transient spectrum (λmax = 340 nm, τ = 0.8 μs) is assigned to an intra-molecular radical cation with a 4-membered ring configuration. The transient species (λmax = 370 nm, τ = 17 μs) formed on reaction of .OH radicals with a 3,3′-thiodipropionyl chloride is assigned to a 5-membered intra-molecular radical cation and remained independent of pH. The OH-adduct (λmax = 350 nm, pH = 11) of 3,3′-thiodipropionamide is observed to undergo transformation to an intra-molecular radical cation (λmax = 370 nm). The transformation is not observed in acidic solutions and only an intra-molecular radical cation (λmax = 370 nm) is observed immediately after the pulse. The contribution of α-thio radicals of 2,2′-thiodiethanamide decreased with pH, and in neutral solutions .OH radicals are observed to react mainly by OH-adduct formation whereas in acidic solutions (pH = 1), as intra-molecular radical cation (λmax = 335 nm) with a 4-membered ring configuration is inferred to be the transient species.
- Gawandi,Mohan,Mittal
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p. 1425 - 1432
(2007/10/03)
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