5597-51-3Relevant academic research and scientific papers
Synthesis, biological evaluation, and structure activity relationship (SAR) study of pyrrolidine amide derivatives as: N -acylethanolamine acid amidase (NAAA) inhibitors
Zhou, Pan,Xiang, Lei,Zhao, Dongsheng,Ren, Jie,Qiu, Yan,Li, Yuhang
supporting information, p. 252 - 262 (2019/03/02)
N-Acylethanolamine acid amidase (NAAA) is one of the key enzymes involved in the degradation of fatty acid ethanolamides (FAEs), especially for palmitoylethanolamide (PEA). Pharmacological blockage of NAAA restores PEA levels, providing therapeutic benefits in the management of inflammation and pain. In the current work, we showed the structure-activity relationship (SAR) studies for pyrrolidine amide derivatives as NAAA inhibitors. A series of aromatic replacements or substituents for the terminal phenyl group of pyrrolidine amides were examined. SAR data showed that small lipophilic 3-phenyl substituents were preferable for optimal potency. The conformationally flexible linkers increased the inhibitory potency of pyrrolidine amide derivatives but reduced their selectivity toward fatty acid amide hydrolase (FAAH). The conformationally restricted linkers did not enhance the inhibitor potency toward NAAA but improved the selectivity over FAAH. Several low micromolar potent NAAA inhibitors were developed, including 4g bearing a rigid 4-phenylcinnamoyl group. Dialysis and kinetic analysis suggested that 4g inhibited NAAA via a competitive and reversible mechanism. Furthermore, 4g showed high anti-inflammatory activities in lipopolysaccharide (LPS) induced acute lung injury (ALI) model, and this effect was blocked by pre-treatment with the PPAR-α antagonist MK886. We anticipate that 4g (E93) will enable a new agent to treat inflammation and related diseases.
A butene liquid crystal compound and its preparation method
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, (2016/10/10)
The invention relates to a butylene type liquid crystal compound and a preparation method of the same. Such compounds are novel negative liquid crystal materials with low viscosity and high absolute value of dielectric constant, have better chemical stability and better stability in light environment and high-temperature environment, and have very high application valve. The butylene type liquid crystal compound is structured as a structural formula shown in the specification, wherein in the structural formula of the compound, R1 refers to hydrogen atom, linear alkyl with 1-8 carbon atoms or linear alkenyl with 2-8 carbon atoms, or alkoxy or alkenyloxy formed by substituting one or two nonadjacent CH2 in the linear alkyl or the linear alkenyl with oxygen atoms, and 0-4 hydrogen atoms in the R1 group are substituted by fluorine; R2 refers to hydrogen atoms or linear alkyl with 1-8 carbon atoms, and 0-4 hydrogen atoms in the R2 group are substituted by fluorine; n = 1 to 2.
The structure - Activity relationship of the antimalarial ozonide arterolane (OZ277)
Dong, Yuxiang,Wittlin, Sergio,Sriraghavan, Kamaraj,Chollet, Jacques,Charman, Susan A.,Charman, William N.,Scheurer, Christian,Urwyler, Heinrich,Tomas, Josefina Santo,Snyder, Christopher,Creek, Darren J.,Morizzi, Julia,Koltun, Maria,Matile, Hugues,Wang, Xiaofang,Padmanilayam, Maniyan,Tang, Yuanqing,Dorn, Arnulf,Brun, Reto,Vennerstrom, Jonathan L.
experimental part, p. 481 - 491 (2010/05/02)
The structure and stereochemistry of the cyclohexane substituents of analogues of arterolane (OZ277) had little effect on potency against Plasmodium falciparum in vitro.Weak base functional groups were not required for high antimalarial potency, but they were essential for high antimalarial efficacy in P. berghei-infected mice. Five new ozonides with antimalarial efficacy and ADME profiles superior or equal to that of arterolane were identified.
