16172-96-6Relevant articles and documents
LPXH TARGETING COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF MAKING AND USING THE SAME
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Paragraph 0138; 0153-0154, (2021/04/17)
LpxH targeting compounds, compositions thereof, as well as methods for for making and using the same are disclosed herein. The LpxH target compounds typically have a structure pursuant to Formula (I) and/or a salt thereof, wherein Rb is selecte
Multitargeted Compounds Derived from (2,5-Dioxopyrrolidin-1-yl)(phenyl)-Acetamides as Candidates for Effective Anticonvulsant and Antinociceptive Agents
Abram, Micha?,Kamiński, Krzysztof,Kamiński, Rafa? M.,Latacz, Gniewomir,Lubelska, Annamaria,Mogilski, Szczepan,Rapacz, Anna
, p. 1996 - 2008 (2020/07/14)
We developed a focused set of original hybrid pyrrolidine-2,5-dione derivatives with potent anticonvulsant and antinociceptive properties. These hybrid compounds demonstrated broad-spectrum protective activity in a range of mouse models, such as the maximal electroshock (MES) test, the pentylenetetrazole-induced seizures (scPTZ), and the 6 Hz (32 mA) seizures. Compound 22 showed the most potent anticonvulsant activity (ED50 MES = 23.7 mg/kg, ED50 6 Hz (32 mA) = 22.4 mg/kg, ED50 scPTZ = 59.4 mg/kg). In addition, 22 revealed potent efficacy in the formalin-induced tonic pain. These in vivo activities of 22 are likely mediated by several targets and may result from the inhibition of central sodium/calcium currents and transient receptor potential vanilloid 1 (TRPV1) receptor antagonism. Finally, the lead compound 22 revealed drug-like absorption, distribution, metabolism, excretion, toxicity (ADME-Tox) properties in the in vitro assays, making it a potential candidate for further development in epilepsy and neuropathic pain indications.
ω-Phthalimidoalkyl Aryl Ureas as Potent and Selective Inhibitors of Cholesterol Esterase
Dato, Florian M.,Sheikh, Miriam,Uhl, Rocky Z.,Schüller, Alexandra W.,Steinkrüger, Michaela,Koch, Peter,Neud?rfl, J?rg-Martin,Gütschow, Michael,Goldfuss, Bernd,Pietsch, Markus
, p. 1833 - 1847 (2018/09/10)
Cholesterol esterase (CEase), a serine hydrolase thought to be involved in atherogenesis and thus coronary heart disease, is considered as a target for inhibitor development. We investigated recombinant human and murine CEases with a new fluorometric assay in a structure–activity relationship study of a small library of ω-phthalimidoalkyl aryl ureas. The urea motif with an attached 3,5-bis(trifluoromethyl)phenyl group and the aromatic character of the ω-phthalimide residue were most important for inhibitory activity. In addition, an alkyl chain composed of three or four methylene groups, connecting the urea and phthalimide moieties, was found to be an optimal spacer for inhibitors. The so-optimized compounds 2 [1-(3,5-bis(trifluoromethyl)phenyl)-3-(3-(1,3-dioxoisoindolin-2-yl)propyl)urea] and 21 [1-(3,5-bis(trifluoromethyl)phenyl)-3-(4-(1,3-dioxoisoindolin-2-yl)butyl)urea] exhibited dissociation constants (Ki) of 1–19 μm on the two CEases and showed either a competitive (2 on the human enzyme and 21 on the murine enzyme) or a noncompetitive mode of inhibition. Two related serine hydrolases—monoacylglycerol lipase and fatty acid amide hydrolase—were inhibited by ω-phthalimidoalkyl aryl ureas to a lesser extent.
