- Preparation method of sulfydryl alkenyl ester compound
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The invention relates to a preparation method of a sulfydryl alkenyl ester compound, belongs to the field of organic chemical synthesis, and aims to solve the problems of high risk of large-scale production and the like, and the synthesis route provided b
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Paragraph 0021; 0028-0030
(2021/07/21)
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- DIRECTED CONJUGATION TECHNOLOGIES
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Among other things, the present disclosure provides technologies for site-directed conjugation of various moieties of interest to target agents. In some embodiments, the present disclosure utilizes target binding moieties to provide high conjugation efficiency and selectivity. In some embodiments, provided technologies are useful for preparing antibody conjugates.
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Paragraph 0912; 0913
(2021/05/29)
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- Synthesis and rational design of anti-inflammatory compounds: N-phenyl-cyclohexenyl sulfonamide derivatives
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The synthesis of (±)-ethyl 6-[N-(2-chloro-4-fluorophenyl)sulfamoyl] cyclohex-1-ene-1-carboxylate (5n) has been reproduced from a method previously described and served as the background for the preparation of a nitro derivative, potentially useful as an a
- Lloret, Gustavo R.,Neto, Alvaro Cunha,Rittner, Roberto,Bitencourt, Michelle,Freitas, Matheus P.,Aquino, Nilton S.
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experimental part
p. 1188 - 1192
(2010/07/13)
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- SUBSTITUTED CYCLOHEXENES
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Disclosed herein are deuterated derivatives of TAK-242 of Formula (I) which are modulators of TLR4 signalling pathway, pharmaceutical compositions thereof and methods of use thereof. Formula (I)
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Page/Page column 65
(2009/03/07)
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- Discovery of novel and potent small-molecule inhibitors of NO and cytokine production as antisepsis agents: Synthesis and biological activity of alkyl 6-(N-substituted sulfamoyl)cyclohex-1-ene-1-carboxylate
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To develop a new therapeutic agent for sepsis, screening of the Takeda chemical library was carried out using mouse macrophages stimulated with lipopolysaccharide (LPS) to identify a new class of small-molecule inhibitors of inflammatory mediator production. The lead compound 5a was discovered, from which a series of novel cyclohexene derivatives I bearing a sulfamoyl and ester group were designed, synthesized and tested for their inhibitory activity against nitric oxide (NO) production. Derivatives I were synthesized by the coupling of sulfonyl chlorides and anilines with concomitant double bond migration in the presence of triethylamine, and phenyl ring substitution and modification of the ester and cyclohexene moieties were carried out. Among the compounds synthesized, ethyl (6R)-6-[N-(2-chloro-4-fluorophenyl)sulfamoyl]- cyclohex-1-ene-1-carboxylate [(R)-(+)-5n, TAK-242] was found to exhibit the most potent suppressive activity for the production of not only NO but also inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) induced by LPS-stimulated mouse macrophages with IC 50 values of 1.8, 1.9 and 1.3 nM, respectively. It shows marked beneficial effects in vivo also. Intravenous administration of (R)-(+)-5n at doses of 0.1 mg/kg or more suppressed the production of NO and various cytokines [TNF-α, IL-6 and IL-1β] in the mouse endotoxin shock model. Furthermore, it protected mice from death dose-dependently and all mice survived at a dose of 3 mg/kg. The minimum effective dose to protect mice from lethality in this model was 0.3 mg/kg, which was consistent with those for inhibitory effects on the production of NO and cytokines. Compound CR)-(+)-5n is currently undergoing clinical trials for the treatment of sepsis.
- Yamada, Masami,Ichikawa, Takashi,Ii, Masayuki,Sunamoto, Mie,Itoh, Katsumi,Tamura, Norikazu,Kitazaki, Tomoyuki
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p. 7457 - 7467
(2007/10/03)
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- Determination of Tautomeric Phenotypes of β-Thioxo Esters and Characterization of the Tautomeric Enethiolic Constituents by Means of 13C NMR Spectroscopy
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The 13C NMR spectra of 28 enethiolizable β-thioxo esters and 6 enethiolizable β-thioxo thioloesters have been recorded in order to establish the tautomeric phenotypes of these compounds.All compounds investigated are essentially enethiolic.The carbonyl-co
- Duus, F.,Hansen, P. E.
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