7501-02-2Relevant articles and documents
Synthetic method of o-phenyl phenoxyethanol
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Paragraph 0035-0082, (2017/08/29)
The invention discloses a synthetic method of o-phenyl phenoxyethanol, and belongs to the field of organic synthesis. The synthetic method comprises the following steps: adding o-phenylphenol, ethylene carbonate and a carbonate catalyst into a reactor, carrying out catalytic reaction at the reaction temperature of 60 to 200 DEG C for 0.5 to 10 hours, after cooling, filtering and recycling the carbonate catalyst from the reaction system so as to obtain the o-phenyl phenoxyethanol, wherein the mass ratio of o-phenylphenol to ethylene carbonate is 1:(0.7 to 2), and the mass of the carbonate catalyst is 0.1% to 15% of the total mass of o-phenylphenol and ethylene carbonate. According to the method provided by the invention, the reaction is carried out by adopting a melting method, dangerous ethylene oxide does not need to be used, a solvent does not need to be used neither, and then the subsequent process of washing and alkali washing and solvent distillation is avoided, so that the method is short in synthetic route and simple in operation, zero emission of pollutants is realized, and the method is safer and more environmentally friendly. Moreover, the carbonate catalyst is filtered and recycled, so that the carbonate catalyst is cyclically utilized, and the energy consumption is effectively reduced.
Substrate activity screening: A fragment-based method for the rapid identification of nonpeptidic protease inhibitors
Wood, Warren J. L.,Patterson, Andrew W.,Tsuruoka, Hiroyuki,Jain, Rishi K.,Ellman, Jonathan A.
, p. 15521 - 15527 (2007/10/03)
A new fragment-based method for the rapid development of novel and distinct classes of nonpeptidic protease inhibitors, Substrate Activity Screening (SAS), is described. This method consists of three steps: (1) a library of N-acyl aminocoumarins with diverse, low molecular weight N-acyl groups is screened to identify protease substrates using a simple fluorescence-based assay, (2) the identified N-acyl aminocoumarin substrates are optimized by rapid analogue synthesis and evaluation, and (3) the optimized substrates are converted to inhibitors by direct replacement of the aminocoumarin with known mechanism-based pharmacophores. The SAS method was successfully applied to the cysteine protease cathepsin S, which is implicated in autoimmune diseases. Multiple distinct classes of nonpeptidic substrates were identified upon screening an N-acyl aminocoumarin library. Two of the nonpeptidic substrate classes were optimized to substrates with >8000-fold improvements in cleavage efficiency for each class. Select nonpeptidic substrates were then directly converted to low molecular weight, novel aldehyde inhibitors with nanomolar affinity to cathepsin S. This study demonstrates the unique characteristics and merits of this first substrate-based method for the rapid identification and optimization of weak fragments and provides the framework for the development of completely nonpeptidic inhibitors to many different proteases.
Imidazole Anticonvulsants: Structure-Activity Relationships of imidazoles
Robertson, David W.,Beedle, E. E.,Lawson, Ron,Leander, J. David
, p. 939 - 943 (2007/10/02)
The imidazoles were found to be potent anticonvulsants.The most potent compound of the series, 1--2-yloxy)ethyl>-1H-imidazole (4), had an ED50 of 15.5 mg/kg aggainst maximal-electroshock-induced seizures in mice after oral administration; the horizontal screen ED50 was 320 mg/kg, revealing that the compound has a protective index of 21.Homologues bearing three- and four-carbon tethers between the imidazole and biphenylyloxy moieties were also active, but their potency was attenuated relative to 4.Congeners with the imidazolyalkoxy moiety at the meta or para positions of biphenyl were also less active.All these compounds were potent potentiators of hexobarbital-induced sleeping time in mice, presumably via the well-known imidazole-mediated inhibition of cytochrome P-450.The structural features governing the anticonvulsant and sleeping-time activities appear to be distinct, but a complete dissociation of these two effects has not been achieved.Thus, the potential of these compounds as clinically useful antiepileptic drugs would appear to be limited.
