- Synthesis and evaluation of 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides as COX-2 and serotonin reuptake inhibitors
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Based on the positive effects of COX-2 inhibitors on depressive symptoms and the desirable physicochemical and biological properties of the morpholine group, a series of novel 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides were designed, synthesized, and tested for their COX-2 inhibitory and serotonin reuptake inhibitory activities in vitro. The structure-activity relationships of the 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides as dual COX-2 and serotonin reuptake inhibitors were determined and discussed in detail. The biological assays indicated that five of the compounds possess good COX-2 selectivity (selectivity index COX-1/COX-2 42.8-158.1). The compound 2-[2-(4-benzyloxyphenyl)morpholino]ethyl 2-(4-iso-butylphenyl)-propanoate hydrochloride (1k) shows better COX-2 inhibitory activity (IC50 = 0.78 μM) than ibuprofen (IC 50 = 7.6 μM), and it simultaneously possesses favorable serotonin reuptake inhibitory activity. A series of novel 2-(2-arylmorpholino)ethyl esters of ibuprofen were tested for their COX-2 inhibitory and serotonin reuptake inhibitory activities in vitro. Most of the compounds possess good COX-2 selectivity. Compound 1k shows better COX-2 inhibitory activity than ibuprofen and possesses favorable serotonin reuptake inhibitory activity. According to the results of the biological assays, 2-arylmorpholine-substituted ibuprofen could be used as a core structure to design novel dual COX-2 and serotonin reuptake inhibitors.
- Dou, Jie,Shi, Lei,Hu, Aixi,Dong, Minyu,Xu, Jiangping,Liu, Ailin,Jiang, Yiping
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- Design, synthesis and biological evaluation of 2-(2-aryl-morpholino-4-yl) ethyl esters of indomethacin as potential cyclooxygenase-2 (COX-2) inhibitors
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A number of novel 2-(2-arylmorpholino-4-yl)ethyl 1-(4-chlorobenzoyl)-5- methoxy-2-methyl-1H-indol-3-acetate hydrochlorides were synthesized and tested for their cyclooxygenase (COX-1 and COX-2) inhibition properties in vitro. Many of these compounds exhibited moderate to good selective COX-2 inhibition, and subtle structural changes in the substituents on the side chain of the ester moiety altered the inhibitory properties significantly. 2-[2-(4-Butoxyphenyl) morpholino-4-yl]ethyl 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-acetate hydrochloride (1f), showed good selective COX-2 inhibitory activity (Selective index (SI) 182), which is comparative with celecoxib (SI 214), a COX-2 inhibitor of diarylpyrazoles. While 2-[2-(2,4-dichloro-5-fluorophenyl)morpholino-4-yl] ethyl 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-acetate hydrochloride (1g), showed greater selective COX-2 inhibitory activity (SI 358) than celecoxib. Both compounds were identified as compromising derivatives in this class to reduce the side effects generated by nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin.
- Shi, Lei,Hu, Aixi,Xu, Jiangping,Jiang, Yiping
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scheme or table
p. 1339 - 1344
(2012/08/29)
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- Convenient electrochemical method for the synthesis of-bromo alkyl aryl ketones
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An electrochemical procedure for the effective-bromination of alkyl aryl ketones in excellent yield has been reported. The simple experimental procedure, catalyst-free conversion, and excellent yield of monobrominated products are the advantages of this method. Copyright
- Kumar, R. Senthil,Kulangiappar,Kulandainathan, M. Anbu
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experimental part
p. 1736 - 1742
(2010/07/05)
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- Asymmetric synthesis, crystal structure, and antidepressant activity of 2-aryl-3-alkyl-5-methyl-2-morpholinol hydrochlorides
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2-Aryl-3-alkyl-5-methyl-2-morpholinols were synthesized from the reactions of chiral 2-aminopropan-1-ol with 2-bromo-1-phenylpropan-1-one, 2-bromo-1-(3-chlorophenyl)propan-1-one, 1-(4-(benzyloxy)phenyl)-2-bromopropan1- one, 2-bromo-1-(6-methoxy- naphthalen-2-yl)propan-1-one, and 1-(4-(benzyloxy)phenyl)pentan-1-one in N-methyl-2-pyrrolidone (NMP), respectively. The 2-aryl-3-alkyl-5-methyl-2-morpholinols were reacted with hydrogen chloride to give the hydrochloride salts with yields of 56%-77%. The structures of the products were proven by means of their 1H NMR, IR, and MS spectroscopic data. The stereochemical properties of representative products were established unambiguously by the X-ray single crystal analysis. The antidepressant activities of the title compounds were assayed by the mouse forced swimming test (FST). The FST results confirm the antidepressant properties of our products.
- Cao, Gao,Hu, Ai-Xi,Xiao, Xin-Rong
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- Resolution of Secondary α-Ketoalcohols Catalyzed by Lipase and Inversioon of Stereochemistry
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Several α-ketoalcohols of synthetic value were resolved using lipase as a catalyst.Lipoprotein lipase (LPL) provided the best rate of hydrolysis and kinetic differentiation.One of these optically pure α-ketoalcohol was converted to (S)-ibuprofen in good optical purity.The stereospecific inversion of (R)-alcohol to (S)-alcohol is described.Key Words Enzymatic resolution; α-Ketoalcohol; (S)-Ibuprofen
- Duh, Tsai-Hui,Wang, Yi-Fong,Wu, Ming-Jung
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p. 579 - 584
(2007/10/02)
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- Process for the preparation of (6-methoxy-2-naphthyl)-(1-bromoethyl)-ketone and its derivatives
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A process is described for the preparation of (6-methoxy-2-naphthyl)-(1-bromoethyl)-ketone or ketals thereof (I), by selective debromination of (5-bromo-6-methoxy-2-naphthyl)-(1-bromoethyl)-ketone or ketals thereof (III) by means of a bromine acceptor in the presence of an acid and of an inert organic solvent. The bromine acceptor is preferably a phenol, a phenol ether or an aromatic ketone. The acid is preferably an halogenidric acid.
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- Process for preparing α-hydroxy-acids and compounds obtained by this process
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The invention relates to a process for preparing α-hydroxy-acids of general formula: STR1 in which R represents hydrogen or a lower alkyl radical and Cy represents a phenyl, naphthyl or heterocyclic radical, these latter three radicals optionally comprising one or more substituents selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy radicals and halogen atoms, process which comprises the treatment of an α-monohalogenated ketone of general formula: STR2 in which R and Cy have the same meaning as above and X represents chlorine, bromine or iodine, in the presence of an aqueous solution of an alkali metal hydroxide, a non-polar organic solvent selected from an aromatic or alicyclic hydrocarbon and oxygen in excess optionally in the presence of an inert gas, the treatment being carried out at a temperature ranging from the boiling temperature of the reaction medium at atmospheric pressure and 240° C. under pressure and the alkali metal so formed is then acidified to obtain the desired acid.
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- A NEW METHOD FOR THE SYNTHESIS OF α-ARYLALKANOIC ACIDS BY THE USE OF 1,2-REARRANGEMENT OF THE ARYL GROUP
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A simple synthetic method of α-arylalkanoic acids was accomplished by the use of a novel 1,2-rearrangement of the aryl group and this method was applied to the syntheses of some biologically important subtances.
- Tsuchihashi, Gen-ichi,Kitajima, Koji,Mitamura, Shuichi
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p. 4305 - 4308
(2007/10/02)
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