ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Abstract 8-Methoxy-2-tetralone (6) can be easily prepared in approximately 50% overall yield star... more Abstract 8-Methoxy-2-tetralone (6) can be easily prepared in approximately 50% overall yield starting from 2-bromophenylacetic acid (1), utilizing a Friedel-Crafts acylation/cyclization, ketone protection, copper(I)-catalyzed methoxylation of the aromatic bromide in the presence of an ester as a co-catalyst, and ketone deprotection.
A method was found to synthesize 1- ( 2,5-dimethoxy-4-(t~uoromethyl)phenyl)-2-a~opropane, 5, and ... more A method was found to synthesize 1- ( 2,5-dimethoxy-4-(t~uoromethyl)phenyl)-2-a~opropane, 5, and its des-a-methyl congener 2-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)aminoethane, 6 the trifluoromethyl analogs of substituted hallucinogenic phenethylamine derivatives such as l-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (3, DOI) that are potent ~- H T ~ A / ~ c agonists. In our hands, 5 and 6 have proven to have affinity for [3H]ketanserin or [12511-3-labeled 5-HT,, sites in rat cortex comparable to or higher than the analogous bromo or iodo analogs. Similarly, 5 and 6 had potency comparable to or slightly greater than that of their bromo or iodo congeners in the two-lever drug discrimination assay in rats trained to discriminate saline from LSD tartrate. The agonist properties of 5 and 6 were evaluated by measuring the accumulation of [3H]inositol monophosphate in cultured cells selectively expressing either 5-HTu or 5-HT2c receptors. In comparison to serotonin (5-HT), compounds 3 (D...
Indan analogs of fen-fluramine and norfenfluramine have reduced neurotoxic potential. PHARMACOL B... more Indan analogs of fen-fluramine and norfenfluramine have reduced neurotoxic potential. PHARMACOL BIOCHEM BEHAV
A method was found to synthesize 1-( 2,5-dimethoxy-4-(t~uoromethyl)phenyl)-2-a~opropane, 5, and i... more A method was found to synthesize 1-( 2,5-dimethoxy-4-(t~uoromethyl)phenyl)-2-a~opropane, 5, and its des-a-methyl congener 2-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)aminoethane, 6, the trifluoromethyl analogs of substituted hallucinogenic phenethylamine derivatives such as l-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (3, DOI) that are potent ~-HT~A/~c agonists. In our hands, 5 and 6 have proven to have affinity for [3H]ketanserin or [12511-3-labeled 5-HT,, sites in rat cortex comparable to or higher than the analogous bromo or iodo analogs. Similarly, 5 and 6 had potency comparable to or slightly greater than that of their bromo or iodo congeners in the two-lever drug discrimination assay in rats trained to discriminate saline from LSD tartrate. The agonist properties of 5 and 6 were evaluated by measuring the accumulation of [3H]inositol monophosphate in cultured cells selectively expressing either 5-HTu or 5-HT2c receptors. In comparison to serotonin (5-HT), compounds 3 (DOI), 5,...
Abstract 8-Methoxy-2-tetralone (6) can be easily prepared in approximately 50% overall yield star... more Abstract 8-Methoxy-2-tetralone (6) can be easily prepared in approximately 50% overall yield starting from 2-bromophenylacetic acid (1), utilizing a Friedel-Crafts acylation/cyclization, ketone protection, copper(I)-catalyzed methoxylation of the aromatic bromide in the presence of an ester as a co-catalyst, and ketone deprotection.
The racemate and the enantiomers of 1-(3-methoxy-4-methyphenyl)-2- aminopropane (6) and racemic 5... more The racemate and the enantiomers of 1-(3-methoxy-4-methyphenyl)-2- aminopropane (6) and racemic 5-methoxy-6-methyl-2-aminoindan (11) were tested for stimulus generalization in the two-lever drug-discrimination paradigm. Both 6 and 11 were found to substitute with high potency in 3,4-(methylenedioxy)methamphetamine (1) and (S)-1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (2) trained rats. In the latter assay, both enantiomers of 6 had identical potencies, but their dose-response curves were not parallel. Racemic 6, but not 11, partially substituted for LSD. Racemic 6 and 11 did not substitute in (S)-amphetamine-trained rats. All of the test compounds were potent inhibitors of [3H]-5-HT uptake into synaptosomes in vitro, with the S enantiomer of 6 being most active. Rat brain monoamine levels were unaltered 1 week following a single high dose (10 or 20 mg/kg, sc) of 6 or 11, or two weeks following a subacute dosing regimen (20 mg/kg, sc, twice a day for 4 days). In addition, radioligand-binding parameters in rat brain homogenate with the 5-HT uptake inhibitor [3H]paroxetine were unchanged after subacute dosing with either racemic 6 or 11. The results indicate that compounds 6 and 11 have animal behavioral pharmacology similar to the methylenedioxy compounds 1 and 2, but that they do not induce the serotonin neurotoxicity that has been observed for the latter two drugs.
The racemate and the enantiomers of 1-(3-methoxy-4-methyphenyl)-2- aminopropane (6) and racemic 5... more The racemate and the enantiomers of 1-(3-methoxy-4-methyphenyl)-2- aminopropane (6) and racemic 5-methoxy-6-methyl-2-aminoindan (11) were tested for stimulus generalization in the two-lever drug-discrimination paradigm. Both 6 and 11 were found to substitute with high potency in 3,4-(methylenedioxy)methamphetamine (1) and (S)-1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (2) trained rats. In the latter assay, both enantiomers of 6 had identical potencies, but their dose-response curves were not parallel. Racemic 6, but not 11, partially substituted for LSD. Racemic 6 and 11 did not substitute in (S)-amphetamine-trained rats. All of the test compounds were potent inhibitors of [3H]-5-HT uptake into synaptosomes in vitro, with the S enantiomer of 6 being most active. Rat brain monoamine levels were unaltered 1 week following a single high dose (10 or 20 mg/kg, sc) of 6 or 11, or two weeks following a subacute dosing regimen (20 mg/kg, sc, twice a day for 4 days). In addition, radioligand-binding parameters in rat brain homogenate with the 5-HT uptake inhibitor [3H]paroxetine were unchanged after subacute dosing with either racemic 6 or 11. The results indicate that compounds 6 and 11 have animal behavioral pharmacology similar to the methylenedioxy compounds 1 and 2, but that they do not induce the serotonin neurotoxicity that has been observed for the latter two drugs.
A method was found to synthesize 1-(2,5-dimethoxy-4-(trifluoromethyl) phenyl)-2-aminopropane, 5, ... more A method was found to synthesize 1-(2,5-dimethoxy-4-(trifluoromethyl) phenyl)-2-aminopropane, 5, and its des-alpha-methyl congener 2-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)aminoethane, 6, the trifluoromethyl analogs of substituted hallucinogenic phenethylamine derivatives such as 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (3, DOI) that are potent 5-HT2A/2C agonists. In our hands, 5 and 6 have proven to have affinity for [3H]ketanserin or [125I]-3-labeled 5-HT2A/2C sites in rat cortex comparable to or higher than the analogous bromo or iodo analogs. Similarly, 5 and 6 had potency comparable to or slightly greater than that of their bromo or iodo congeners in the two-lever drug discrimination assay in rats trained to discriminate saline from LSD tartrate. The agonist properties of 5 and 6 were evaluated by measuring the accumulation of [3H]inositol monophosphate in cultured cells selectively expressing either 5-HT2A or 5-HT2C receptors. In comparison to serotonin (5-HT), compounds 3 (DOI), 5, and 6 were equally efficacious and full agonists at the 5-HT2C receptor. Similarly, 3 and 5 produced equivalent responses at the 5-HT2A receptor as compared to 5-HT. In contrast, 6, the alpha-desmethyl analog of 5, was only half as potent at stimulating inositol monophosphate accumulation at the 5-HT2A receptor. In conclusion, the title compound 5 and its alpha-desmethyl congener 6 appear to be the most potent of the so-called hallucinogenic amphetamine 5-HT agonists reported to date. Further, the reduced efficacy of 6 at the 5-HT2A receptor may offer at least a partial explanation for the observed higher in vivo potencies of alpha-methyl-substituted compounds in this series.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Abstract 8-Methoxy-2-tetralone (6) can be easily prepared in approximately 50% overall yield star... more Abstract 8-Methoxy-2-tetralone (6) can be easily prepared in approximately 50% overall yield starting from 2-bromophenylacetic acid (1), utilizing a Friedel-Crafts acylation/cyclization, ketone protection, copper(I)-catalyzed methoxylation of the aromatic bromide in the presence of an ester as a co-catalyst, and ketone deprotection.
A method was found to synthesize 1- ( 2,5-dimethoxy-4-(t~uoromethyl)phenyl)-2-a~opropane, 5, and ... more A method was found to synthesize 1- ( 2,5-dimethoxy-4-(t~uoromethyl)phenyl)-2-a~opropane, 5, and its des-a-methyl congener 2-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)aminoethane, 6 the trifluoromethyl analogs of substituted hallucinogenic phenethylamine derivatives such as l-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (3, DOI) that are potent ~- H T ~ A / ~ c agonists. In our hands, 5 and 6 have proven to have affinity for [3H]ketanserin or [12511-3-labeled 5-HT,, sites in rat cortex comparable to or higher than the analogous bromo or iodo analogs. Similarly, 5 and 6 had potency comparable to or slightly greater than that of their bromo or iodo congeners in the two-lever drug discrimination assay in rats trained to discriminate saline from LSD tartrate. The agonist properties of 5 and 6 were evaluated by measuring the accumulation of [3H]inositol monophosphate in cultured cells selectively expressing either 5-HTu or 5-HT2c receptors. In comparison to serotonin (5-HT), compounds 3 (D...
Indan analogs of fen-fluramine and norfenfluramine have reduced neurotoxic potential. PHARMACOL B... more Indan analogs of fen-fluramine and norfenfluramine have reduced neurotoxic potential. PHARMACOL BIOCHEM BEHAV
A method was found to synthesize 1-( 2,5-dimethoxy-4-(t~uoromethyl)phenyl)-2-a~opropane, 5, and i... more A method was found to synthesize 1-( 2,5-dimethoxy-4-(t~uoromethyl)phenyl)-2-a~opropane, 5, and its des-a-methyl congener 2-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)aminoethane, 6, the trifluoromethyl analogs of substituted hallucinogenic phenethylamine derivatives such as l-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (3, DOI) that are potent ~-HT~A/~c agonists. In our hands, 5 and 6 have proven to have affinity for [3H]ketanserin or [12511-3-labeled 5-HT,, sites in rat cortex comparable to or higher than the analogous bromo or iodo analogs. Similarly, 5 and 6 had potency comparable to or slightly greater than that of their bromo or iodo congeners in the two-lever drug discrimination assay in rats trained to discriminate saline from LSD tartrate. The agonist properties of 5 and 6 were evaluated by measuring the accumulation of [3H]inositol monophosphate in cultured cells selectively expressing either 5-HTu or 5-HT2c receptors. In comparison to serotonin (5-HT), compounds 3 (DOI), 5,...
Abstract 8-Methoxy-2-tetralone (6) can be easily prepared in approximately 50% overall yield star... more Abstract 8-Methoxy-2-tetralone (6) can be easily prepared in approximately 50% overall yield starting from 2-bromophenylacetic acid (1), utilizing a Friedel-Crafts acylation/cyclization, ketone protection, copper(I)-catalyzed methoxylation of the aromatic bromide in the presence of an ester as a co-catalyst, and ketone deprotection.
The racemate and the enantiomers of 1-(3-methoxy-4-methyphenyl)-2- aminopropane (6) and racemic 5... more The racemate and the enantiomers of 1-(3-methoxy-4-methyphenyl)-2- aminopropane (6) and racemic 5-methoxy-6-methyl-2-aminoindan (11) were tested for stimulus generalization in the two-lever drug-discrimination paradigm. Both 6 and 11 were found to substitute with high potency in 3,4-(methylenedioxy)methamphetamine (1) and (S)-1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (2) trained rats. In the latter assay, both enantiomers of 6 had identical potencies, but their dose-response curves were not parallel. Racemic 6, but not 11, partially substituted for LSD. Racemic 6 and 11 did not substitute in (S)-amphetamine-trained rats. All of the test compounds were potent inhibitors of [3H]-5-HT uptake into synaptosomes in vitro, with the S enantiomer of 6 being most active. Rat brain monoamine levels were unaltered 1 week following a single high dose (10 or 20 mg/kg, sc) of 6 or 11, or two weeks following a subacute dosing regimen (20 mg/kg, sc, twice a day for 4 days). In addition, radioligand-binding parameters in rat brain homogenate with the 5-HT uptake inhibitor [3H]paroxetine were unchanged after subacute dosing with either racemic 6 or 11. The results indicate that compounds 6 and 11 have animal behavioral pharmacology similar to the methylenedioxy compounds 1 and 2, but that they do not induce the serotonin neurotoxicity that has been observed for the latter two drugs.
The racemate and the enantiomers of 1-(3-methoxy-4-methyphenyl)-2- aminopropane (6) and racemic 5... more The racemate and the enantiomers of 1-(3-methoxy-4-methyphenyl)-2- aminopropane (6) and racemic 5-methoxy-6-methyl-2-aminoindan (11) were tested for stimulus generalization in the two-lever drug-discrimination paradigm. Both 6 and 11 were found to substitute with high potency in 3,4-(methylenedioxy)methamphetamine (1) and (S)-1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (2) trained rats. In the latter assay, both enantiomers of 6 had identical potencies, but their dose-response curves were not parallel. Racemic 6, but not 11, partially substituted for LSD. Racemic 6 and 11 did not substitute in (S)-amphetamine-trained rats. All of the test compounds were potent inhibitors of [3H]-5-HT uptake into synaptosomes in vitro, with the S enantiomer of 6 being most active. Rat brain monoamine levels were unaltered 1 week following a single high dose (10 or 20 mg/kg, sc) of 6 or 11, or two weeks following a subacute dosing regimen (20 mg/kg, sc, twice a day for 4 days). In addition, radioligand-binding parameters in rat brain homogenate with the 5-HT uptake inhibitor [3H]paroxetine were unchanged after subacute dosing with either racemic 6 or 11. The results indicate that compounds 6 and 11 have animal behavioral pharmacology similar to the methylenedioxy compounds 1 and 2, but that they do not induce the serotonin neurotoxicity that has been observed for the latter two drugs.
A method was found to synthesize 1-(2,5-dimethoxy-4-(trifluoromethyl) phenyl)-2-aminopropane, 5, ... more A method was found to synthesize 1-(2,5-dimethoxy-4-(trifluoromethyl) phenyl)-2-aminopropane, 5, and its des-alpha-methyl congener 2-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)aminoethane, 6, the trifluoromethyl analogs of substituted hallucinogenic phenethylamine derivatives such as 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (3, DOI) that are potent 5-HT2A/2C agonists. In our hands, 5 and 6 have proven to have affinity for [3H]ketanserin or [125I]-3-labeled 5-HT2A/2C sites in rat cortex comparable to or higher than the analogous bromo or iodo analogs. Similarly, 5 and 6 had potency comparable to or slightly greater than that of their bromo or iodo congeners in the two-lever drug discrimination assay in rats trained to discriminate saline from LSD tartrate. The agonist properties of 5 and 6 were evaluated by measuring the accumulation of [3H]inositol monophosphate in cultured cells selectively expressing either 5-HT2A or 5-HT2C receptors. In comparison to serotonin (5-HT), compounds 3 (DOI), 5, and 6 were equally efficacious and full agonists at the 5-HT2C receptor. Similarly, 3 and 5 produced equivalent responses at the 5-HT2A receptor as compared to 5-HT. In contrast, 6, the alpha-desmethyl analog of 5, was only half as potent at stimulating inositol monophosphate accumulation at the 5-HT2A receptor. In conclusion, the title compound 5 and its alpha-desmethyl congener 6 appear to be the most potent of the so-called hallucinogenic amphetamine 5-HT agonists reported to date. Further, the reduced efficacy of 6 at the 5-HT2A receptor may offer at least a partial explanation for the observed higher in vivo potencies of alpha-methyl-substituted compounds in this series.
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