66924-20-7Relevant academic research and scientific papers
Discovery of N-hydroxy-3-alkoxybenzamides as direct acid sphingomyelinase inhibitors using a ligand-based pharmacophore model
Yang, Kan,Nong, Keyi,Gu, Qinlan,Dong, Jibin,Wang, Jinxin
, p. 389 - 400 (2018/04/12)
Acid sphingomyelinase (ASM) has been shown to be involved in many physiological processes, emerging to be a promising drug target. In this study, we constructed a ligand-based pharmacophore model of ASM inhibitors and applied this model to optimize the lead compound α-mangostin, a known inhibitor of ASM. 23 compounds were designed and evaluated in vitro for ASM inhibition, of these, 10 compounds were found to be more potent than α-mangostin. This high hit ratio confirmed that the presented model is very effective and practical. The most potent hit, 1c, was found to selectively and competitively inhibit the enzyme and inhibit the generation of ceramide in a dose-dependent manner. Furthermore, 1c showed favorable anti-apoptosis and anti-inflammatory activity. Interactions with key residues and the Zn2+ cofactor of 1c were found by docking simulation. These results provide promising leads and important guidance for further development of efficient ASM inhibitors and drug candidates.
HETEROAROMATIC DERIVATIVES AND PHARMACEUTICAL APPLICATIONS THEREOF
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Paragraph 00327, (2015/11/10)
Provided herein are novel heteroaromatic derivatives, or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a prodrug, a pharmaceutically acceptable salt or a prodrug thereof, and pharmaceutical compositions containing such compounds. Also provided herein are uses of such compounds or pharmaceutical compositions thereof in the manufacture of a medicament for treating respiratory diseases, especially chronic obstructive pulmonary disease (COPD).
Discovery and structural modification of 1-phenyl-3-(1-phenylethyl)urea derivatives as inhibitors of complement
Zhang, Mei,Yang, Xiao-Ying,Tang, Wei,Groeneveld, Tom W. L.,He, Pei-Lan,Zhu, Feng-Hua,Li, Jia,Lu, Wei,Blom, Anna M.,Zuo, Jian-Ping,Nan, Fa-Jun
supporting information; experimental part, p. 317 - 321 (2012/05/20)
A series of 1-phenyl-3-(1-phenylethyl)urea derivatives were identified as novel and potent complement inhibitors through structural modification of the original compound from high-throughput screening. Various analogues (7 and 13-15) were synthesized and identified as complement inhibitors, with the introduction of a five- or six-carbon chain (7c, 7d, 7k, 7l, and 7o) greatly improving their activity. Optimized compound 7l has an excellent inhibition activity with IC50 values as low as 13 nM. We demonstrated that the compound 7l inhibited C9 deposition through the classical, the lectin, and the alternative pathways but had no influence on C3 and C4 depositions.
Selective Type IV Phosphodiesterase Inhibitors as Antiasthmatic Agents. The Syntheses and Biological Activities of 3-(Cyclopentyloxy)-4-methoxybenzamides and Analogues
Ashton, Michael J.,Cook, David C.,Fenton, Garry,Karlsson, Jan-Anders,Palfreyman, Malcolm N.,et al.
, p. 1696 - 1703 (2007/10/02)
The syntheses and biological activities of a number of benzamide derivatives, designed from rolipram, which are selective inhibitors of cyclic AMP-specific phosphodiesterase (PDE IV), are described.The effects of changes to the alkoxy groups, amide linkag
Influence of lateral alkoxy substitution on mesomorphic properties of copper complexes
Berdague, Philippe,Perez, Felix,Courtieu, Jacques,Bayle, Jean-Pierre
, p. 335 - 343 (2007/10/02)
Coordination complexes between copper and some lateral alkoxy chain-substituted N-(4-(4'-alkoxybenzoyloxy)salicylidene)-4-n-butylaniline have been synthesized.The lateral chain was introduced on the outer ring bearing the ester function.In the case of a 3,4-disubstitution, the mesomorphic behavior is related to the number of carbons in the terminal chain.If this is too small, the mesomorphic properties of the complexes disappear.In contrast, copper complexes are liquid crystalline and show more ordered phases by comparison with the free ligand.In case of a 2,4-disubstitution, the phases are nematic and the clearing temperatures are near room temperature, but the observed phases are essentially monotropic for the ligands, as well as for the complexes.Keywords: nematic / copper complex / lateral substitution / Schiff base
Selective etherification of polyhydroxybenzenes using PEG 200 as solvent or cosolvent
Berdague, P.,Perez, F.,Courtieu, J.,Bayle, J. P.
, p. 475 - 480 (2007/10/02)
The monoalkylation of hydroquinone is performed using PEG 200 as a solvent or a cosolvent.The effect on the selectivity of the base strength, the temperature, and the percentage of cosolvent are discussed.The substituted phenols were found to behave differently upon etherification.When a carboxylic function is present in the ring, the hydroxybenzoic acids were selectively etherified using pure PEG and sodium hydroxyde as a base.Substituted diphenols were selectively etherified using a mixture of PEG and dioxan and potassium hydrogencarbonate as a base.Keywords - etherification / selectivity / polyhydroxybenzenes / polyethylene glycol
An improved method for the synthesis of 5-aryl-3-methyl-2-methylimino-1,3,4-oxadiazoles
Kane,Staeger
, p. 1 - 11 (2007/10/02)
5-Aryl-3-methyl-2-methylimino-1,3,4-oxadiazoles were prepared in 54-81% yields by the mercuric oxide-induced cyclizations of 1-aroyl-2,4,-dimethylthiosemicarbazides.
