A series of 2-amino-1-(4-substituted-2,5-dimethoxyphenyl)butanes (Table V) was prepared as analogues of (R)-2-amino-1-(2,5-dimethoxy-4-methylphenyl)butane (1a). 1-(2,5-Dimethoxyphenyl)-2-(N-phthalimido)butane (7) was utilized as a synthetic intermediate common to many of the target compounds. Animal data are presented indicating that most of these analogues have low hallucinogenic potential....
Bufotenine (5-hydroxy-N,N-dimethyltryptamine) has been reported to be behaviorally inactive or only very weakly active in man and animals; this may be a consequence of its low partition coefficient and resultant inability to penetrate the blood--brain barrier. The acetyl, propionyl, butyryl, isobutyryl, and pivalyl esters of bufotenine were prepared for future pharmacological evaluation....
The compounds 1-(2-methyl-1,3-benzodioxol-5-yl)-2-aminopropane and 1-(2,2-dimethyl-1,3-benzodioxol-5-yl)-2-aminopropane were synthesized and evaluated for pharmacologic effects in mice. These can be viewed as analogues of the known psychotomimetic agent 3,4-(methylenedioxy)amphetamine (MDA). Their hydrochloride salts were compared with MDA for their ability to increase spontaneous motor...
Autoxidation of the bis(O-demethyl)-p-hydroquinone metabolite of the psychotomimetic amine 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) at pH 7.4 leads exclusively to a bicyclic imino quinone. This imino quinone is a good alkylating agent, forming covalent adducts via 1,4 addition to thiols. The autoxidation appears to be dependent on trace metal catalysis and is dramatically inhibited...
An hallucinogen analogue, trans-2-(2,5-dimethoxy-4-methylphenyl)cyclopropylamine (DMCPA), was resolved into ints two enantiomers by fractional crystallization of salts with d- or l-O,O-dibenzoyltartaric acid. A comparison of the ORD and CD curves of the N-5-bromosalicylidene derivatives of trans-2-phenylcyclopropylamine of known absolute configuration and of the title compound established the...
Hallucinogenic phenylalkylamine and N,N-dimethyltryptamine analogues are known to affect serotonergic systems both in vivo and in vitro. Using a rat stomach fundus model, the 5-HT receptor binding affinities of several of these analogues were determined and compared. The most behaviorally potent analogues examined, DOB, DOM, and 5-methoxy-N,N-dimethyltryptamine, were found to possess rather...
A series of ring-substituted hallucinogenic amphetamines has been analyzed using molecular connectivity. A correlating equation has been found between potency and connectivity terms. The equation permits an interpretation of SAR. The equation is capable of predicting potency for amphetamines not in the list and mescalines and tryptamines.
Regiospecific syntheses of the three monomethylthio analogues of 1-(2,4,5-trimethoxyphenyl)-2-aminopropane are described. The three isomeric amines were evaluated for potential psychotomimetic potency using the rabbit hyperthermia assay. Enantiomeric compositions and time-concentration curves in rat brains were determined following intraperitoneal administration of each compound. The biological...
Replacement of the 4-methoxy of mescaline with higher alkyl homologues or with bromine led to increased activity at serotonin receptors in a sheep umbilical artery preparation. This activity appears correlated with lipophilicity, as measured by 1-octanol-water partition coefficients, but drops off when the 4-substituent is about five atoms in length. It is suggested that 3,4,5-trisubhe...
A homologous series of 4-alkyl-2,5-dimethoxyphenylisopropylamines (alkyl = H through n-C5H11 and t-C4H9) was synthesized and compared with mescaline as serotonin agonists in a sheep umbilical preparation. The three-carbon homolog 6d was found to be the most potent of the straight-chain series in accordance with its observed psychotomimetic effectiveness in man.
In an attempt to relate the hallucinogenic potencies in man of some biologically important amphetamines and phenethylamines, the 1-octanol-water partition coefficients for 11 amphetamines were determined. Using these values and published Hansch pi constants, the log P for 17 additional amines was estimated. It was found that lipophilicity, as measured by the log of the partition coefficient,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT.beta.-Chloroethylamines related to mescalinePaul D. CooperCite this: J. Med. Chem. 1973, 16, 9, 1057–1059Publication Date (Print):September 1, 1973Publication History Published online1 May 2002Published inissue 1 September 1973https://pubs.acs.org/doi/10.1021/jm00267a026https://doi.org/10.1021/jm00267a026research-articleACS PublicationsRequest reuse...
ADVERTISEMENT RETURN TO ISSUEPREVArticleHallucinogenic Drugs and their Psychotherapeutic Use.Harvey M. ZelnickCite this: J. Med. Chem. 1964, 7, 1, 122Publication Date (Print):January 1, 1964Publication History Published online1 May 2002Published inissue 1 January 1964https://pubs.acs.org/doi/10.1021/jm00331a036https://doi.org/10.1021/jm00331a036research-articleACS PublicationsRequest reuse...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of Phenethylamines Related to Mescaline as Possible Psychotomimetic Agents1Orrie M. Friedman, K. N. Parameswaran, and Sumner BursteinCite this: J. Med. Chem. 1963, 6, 3, 227–229Publication Date (Print):May 1, 1963Publication History Published online1 May 2002Published inissue 1 May...