1006-59-3Relevant articles and documents
Cyclohexanol analogues are positive modulators of GABAA receptor currents and act as general anaesthetics in vivo
Hall, Adam C.,Griffith, Theanne N.,Tsikolia, Maia,Kotey, Francesca O.,Gill, Nikhila,Humbert, Danielle J.,Watt, Erin E.,Yermolina, Yuliya A.,Goel, Shikha,El-Ghendy, Bahaa,Hall, C. Dennis
, p. 175 - 181 (2011)
GABAA receptors meet all the pharmacological criteria required to be considered important general anaesthetic targets. In the following study, the modulatory effects of various commercially available and novel cyclohexanols were investigated on recombinant human γ-aminobutyric acid (GABA A, α1β2γ2s) receptors expressed in Xenopus oocytes, and compared to the modulatory effects on GABA currents observed with exposures to the intravenous anaesthetic agent, propofol. Submaximal EC20 GABA currents were typically enhanced by co-applications of 3-300 μM cyclohexanols. For instance, at 30 μM 2,6-diisopropylcyclohexanol (a novel compound) GABA responses were increased ～ 3-fold (although similar enhancements were achieved at 3 μM propofol). As regards rank order for modulation by the cyclohexanol analogues at 30 μM, the % enhancements for 2,6-dimethylcyclohexanol ～ 2,6-diethylcyclohexanol ～ 2,6-diisopropylcyclohexanol ～ 2,6-di-sec-butylcyclohexanol ?2,6-di-tert-butylcyclohexanol ～ 4-tert-butylcyclohexanol > cyclohexanol ～ cyclopentanol ～ 2-methylcyclohexanol. We further tested the potencies of the cyclohexanol analogues as general anaesthetics using a tadpole in vivo assay. Both 2,6-diisopropylcyclohexanol and 2,6- dimethylcyclohexanol were effective as anaesthetics with EC50s of 14.0 μM and 13.1 μM respectively, while other cyclohexanols with bulkier side chains were less potent. In conclusion, our data indicate that cyclohexanols are both positive modulators of GABAA receptors currents and anaesthetics. The positioning and size of the alkyl groups at the 2 and 6 positions on the cyclohexanol ring were critical determinants of activity.
Halide-free ethylation of phenol by multifunctional catalysis using phosphinite ligands
Carrion, M. Carmen,Cole-Hamilton, David J.
, p. 4527 - 4529 (2006)
The ortho-alkylation of phenols or aniline by catalytic C-H activation and multifunctional catalysis is described. The Royal Society of Chemistry 2006.
Reductive dealkylation of anisole and phenetole: Towards practical lignin conversion
Strassberger, Zea,Tanase, Stefania,Rothenberg, Gadi
, p. 5246 - 5249 (2011)
We present and develop alternative catalysts for biomass conversion and specifically lignin conversion into aromatics. Unlike the conventional CoMo and NiMo formulations, our catalysts can convert low-sulfur feedstocks. A set of five magnesia-alumina mixed oxides were screened in the hydrodealkylation of alkyl phenyl ethers as lignin model compounds. The typical selectivity to phenol is 30-75 %. Interestingly, we saw that the more basic the catalyst, the higher the selectivity for phenol. The results concur with the formation of phenoxide (PhO-) and RH3+ fragments on the catalyst surface. These can then react with H+ and H- species formed by the hydrogen dissociation on the MgO surface, giving phenol and hydrocarbons. We conclude that magnesia-alumina mixed oxides are attractive candidates for catalyzing lignin breakdown. These catalysts are highly stable, inexpensive, and readily available .
QSAR for the cytotoxicity of 2-alkyl or 2,6-dialkyl, 4-X-phenols: The nature of the radical reaction
Selassie, Cynthia D.,Verma, Rajeshwar P.,Kapur, Sanjay,Shusterman, Alan J.,Hansch, Corwin
, p. 1112 - 1117 (2002)
In a continuation of studies on the radical mediated toxicity of phenols to leukemia cells, a set of di- and tri-substituted phenols with mostly alkyl substituents in the ortho position were examined. These analogs are similar in structure to the commercial antioxidants BHA and BHT. A QSAR analysis of their growth inhibitory constants led to the formulation of this simple but unusual equation based on 18 congeners: log 1/C = -0.47Es-2 + 2.42RR + 2.43; r3 = 0.934 ES-2 is the Taft steric parameter for the larger of the two ortho substituents while ER is Otsu's radical parameter, which was originally defined to correlate radical reactions.
Preparation method of propofol and structural analogues of propofol
-
Paragraph 0091, (2017/08/28)
The invention relates to a preparation method of propofol and structural analogues of propofol. The preparation method comprises the steps as follows: preparing an intermediate from p-hydroxybenzoic acid and alkyl alcohol as raw materials under the action of a solid acid catalyst, and then preparing a target product by a decarboxylase reaction. The preparation method has the characteristics of being green in synthesis, realizing biotransformation, causing little pollution, producing few by-products and the like, and is suitable for industrial production; the purity of the prepared products such as propofol is 99.6% or higher, which meets various medicinal standards.
Selective catalytic conversion of guaiacol to phenols over a molybdenum carbide catalyst
Ma, Rui,Cui, Kai,Yang, Le,Ma, Xiaolei,Li, Yongdan
supporting information, p. 10299 - 10301 (2015/06/25)
An activated carbon supported α-molybdenum carbide catalyst (α-MoC1-x/AC) showed remarkable activity in the selective deoxygenation of guaiacol to substituted mono-phenols in low carbon number alcohol solvents. Combined selectivities of up to 85% for phenol and alkylphenols were obtained at 340°C for α-MoC1-x/AC at 87% conversion in supercritical ethanol. The reaction occurs via consecutive demethylation followed by a dehydroxylation route instead of a direct demethoxygenation pathway.
Peroxynitrite generation from a NO-releasing nitrobenzene derivative in response to photoirradiation
Ieda, Naoya,Nakagawa, Hidehiko,Horinouchi, Taeko,Peng, Tao,Yang, Dan,Tsumoto, Hiroki,Suzuki, Takayoshi,Fukuhara, Kiyoshi,Miyata, Naoki
supporting information; experimental part, p. 6449 - 6451 (2011/06/27)
Photocontrollable ONOO- generation from a nitrobenzene derivative was demonstrated. The designed compound released NO in response to photoirradiation, and the resulting semiquinone reduced molecular oxygen to generate O2-; reaction of the two generated ONOO -, as confirmed with an ONOO- fluorescent probe, HKGreen-3.
Derivatives of pyrimido[6,1-a]isoquinolin-4-one
-
, (2008/06/13)
The invention provides compounds or salts thereof of the general formula (I): wherein each of R1and R2 independently represents a C1-6 alkyl or C2-7 acyl group; X represents OCH2 or a group CR3R4; wherein each of R3 or R4 independently represents a hydrogen atom or a C1-3 alkyl group; R5 represents a hydrogen atom or a C1-3 alkyl, C2-3 alkenyl or C2-3 alkynyl group; R6 represents a hydrogen atom or a C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, amino, C1-6 alkylamino, di(C1-6) alkylamino or C2-7 acylamino group; each of R7 and R8 independently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkylthio, C1-6 alkoxy, C3-6 cycloalkyl; and R9 represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkylthio, C1-6 alkoxy or C3-6 cycloalkyl group. The compounds or salts thereof are useful for treatment of respiratory disorders such as asthma. Compounds of the invention have a longer duration of action than the known compound trequinsin (9,10-dimethoxy-3 methyl-2-mesitylimino-2,3,6,7-tetrahydro-4H-pyrimido[6,1-a]isoquinolin-4-one).
Antihydrophobic cosolvent effects for alkylation reactions in water solution, particularly oxygen versus carbon alkylations of phenoxide ions
Breslow, Ronald,Groves, Kevin,Mayer, M. Uljana
, p. 3622 - 3635 (2007/10/03)
Antihydrophobic cosolvents such as ethanol increase the solubility of hydrophobic molecules in water, and they also affect the rates of reactions involving hydrophobic surfaces. In simple reactions of hydrocarbons, such as the Diels-Alder dimerization of 1,3-cyclopentadiene, the rate and solubility data directly reflect the geometry of the transition state, in which some hydrophobic surface becomes hidden. In reactions involving polar groups, such as alkylations of phenoxide ions or SN1 ionizations of alkyl halides, cosolvents in water can have other effects as well. However, solvation of hydrophobic surfaces is still important. By the use of structure-reactivity relationships, and comparing the effects of ethanol and DMSO as solvents, it has been possible to sort out these effects. The conclusions are reinforced by an ab initio computer model for hydrophobic solvation. The result is a sensible transition state for phenoxide ion as a nucleophile, using its oxygen n electrons to avoid loss of conjugation. The geometry of alkylation of aniline is very different, involving packing (stacking) of the aniline ring onto the phenyl ring of a benzyl group in the benzylation reaction. The alkylation of phenoxide ions by benzylic chlorides can occur both at the phenoxide oxygen and on ortho and para positions of the ring. Carbon alkylation occurs in water, but not in nonpolar organic solvents, and it is observed only when the phenoxide has at least one methyl substituent ortho, meta, or para. The effects of phenol substituents and of antihydrophobic cosolvents on the rates of the competing alkylation processes indicate that in water the carbon alkylation involves a transition state with hydrophobic packing of the benzyl group onto the phenol ring. The results also support our conclusion that oxygen alkylation uses the n electrons of the phenoxide oxygen as the nucleophile and does not have hydrophobic overlap in the transition state. The mechanisms and explanations for competing oxygen and carbon alkylations differ from previous proposals by others.
Design, synthesis and biological testing of a novel series of anti-inflammatory drugs
Duffy,Dearden,Rostron
, p. 1505 - 1514 (2007/10/03)
Many of the non-steroidal anti-inflammatory drugs (NSAIDs) currently marketed produce severe gastro-toxic side effects. The benefits of producing NSAIDs without these side effects are obvious, particularly for patients requiring long-term therapy. The aim of this investigation was to produce novel NSAIDs, based on paracetamol, that exhibit little or no gastro-toxicity. The work covers design, synthesis and testing of 13 drug candidates. The analgesic and anti-inflammatory potencies of the drug candidates were measured using the mouse abdominal constriction assay and the carrageenan-induced rat paw oedema assay, respectively. The stomachs of the rats were examined post-mortem, to assess the gastro-toxicity of the drugs. Of the 13 compounds described herein, 11 were shown to possess analgesic activity at 2-10 times the potency of aspirin, while 8 demonstrated anti-inflammatory activity at 3-10 times the potency of aspirin. Significantly, all of the compounds showed very low gastro-toxicity when compared with aspirin. The results of this study indicate that it is possible to develop novel, potent NSAIDs based on the structure of paracetamol. These compounds have the advantage of demonstrating much lower gastro-toxicity than NSAIDs currently available. Drugs of this type may, in future, provide effective treatments for inflammatory disorders.
