Aminotetralins aminotetralin

Dezocine (30) represents a class of bridged aminotetralins possessing morphine-like analgesic properties. It appears to be roughly equivalent in potency and addiction potential to morphine. The molecule combines molecular features of precedent aminotetralins and benzomor-phans and its structure fits the classical Morphine Rule. The 1-enantiomer is the more active and the p-epimer (equatorial NHj) is the active diastereomer. 

Fuller, R.W. Wong, D.T. Snoddy, H.D. and Bymaster, F.P. Comparison of the effects of 6-chloro-2-aminotetralin and of Org 6582. a related chloramphetamine analog, on brain serotonin metabolism in rats. 

Ethonam (99), an imidazole derivative with a very different substitution pattern, is also reported to possess antifungal activity. To prepare it, alkylation of aminotetralin 94 with methylchloro-acetate gives the glycine derivative 95. Heating with formic acid then affords the amide 96 this compound is then reacted with ethyl formate to yield hydroxymethylene ester 97. Reaction with isothio-cyanic acid gives the imidazole-2-thiol 98. (The... 

Suzuki, T. et al., The D3-receptor agonist (+/-)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) attenuates morphine-induced hyperlocomolion in mice, Neurosci. Lett., 187, 45, 1995. 

Another series of rigid analogs that have been examined to some degree are the aminotetralins with the general formula of Structure 17. If, as might be... 

Violland et al. (241) examined several methoxy-substituted 2-aminotetralins as hallucinogen analogs. Characterized in mice and dogs, these produced ataxia, sedation, and analgesia. 

The lack of clear-cut hallucinogen-type activity for the 2-aminotetralins could be explained in several ways. The known deleterious effect of molecular bulk in the alpha-position would seem to direct attention to the steric effect of the reduced ring of the tetralins as detrimental to activity. In 18b, however, it has been noted (156) that the 5-methoxy group is forced out of plane by the adjacent 6-methyl and 4-methylene groups. The importance to activity of maintaining the methoxy groups coplanar with the aromatic ring has been emphasized earlier. Both substituent orientation and N-alkylation must also be important to activity, and it may not be realistic to make direct comparisons between the phenethyl-amines and the 2-aminotetralins. 

Violland, R., Violland-Duperret, N., Pacheco, H., Trouiller, G., and LeBlanc, A. (1971) Potential psychotropic compounds. VIII. Synthesis and pharmacological activity of 2-aminotetralins related to psychotomimetics. Bull. Chim. Ther., 6 196-202. 

HPLC, using a Crownpack CR column containing an 18-crown-6-type chiral crown ether, served to separate and resolve the enantiomers of 5,6-dihydroxy-2-aminotetraline (132a) and 6,7-dihydroxy-2-aminotetraline (132b) at pH 2.0 LOQ for enantiomeric impurities was <0.1%308. 

The dopamine D2 agonist SAR area has been reviewed by Hacksell and coworkers from the perspective of stereochemistry and pharmacological profiles of the enantiomers of the compounds synthesized by that research group during a period of 10 years. The structural classes surveyed were 3-phenylpiperidines, 2-aminotetralins and their ring-methylated analogues and octahydrobenzo[/]quinolines (OHB[f]Qs) [60]. 

Levesque D, Diaz J, Pilon C, Martres MP, Giros B, Souil E, Schott D, Morgat JL, Schwartz JC, Sokoloff P (1992) Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin, Proc Natl Acad Sci USA 89 8155-8159... 

Extremely active compounds are found among 2-aminotetralines. 6,7-Dihydroxy-2-aminotetraline (4.85, ADTN) and its A-(n-propyl) derivative are well-studied 2-aminotetraline derivatives. Nomifensine (4.83) is related to these aminotetralines and is used as an antidepressant drug. The catechol analog of nomifensine (with two hydroxyls on the 4-phenyl ring) is also a potent inhibitor of NE and DA uptake. 

The strucmre of nortriptyline (18-1) depicted above in an admittedly biased projection suggested 4-aryl-1-aminotetralins as possible topological analogues by the formal opening of the seven-membered ring and then cyclizing the side chain. The preparation of the first of these agents starts with 4,4-diphenylbutyric acid (19-1). 

Cyclization of the acid chloride by means of aluminum chloride gives tetralone (19-2). This is then converted to its A -methylimine (19-3) by means of methylamine and titanium tetrachloride. That intermediate is next reduced with sodium boro-hydride to give a mixture of cis and trans aminotetralins (19-4). The tmns isomer tametraline (19-5) is separated by fractional crystallization of the hydrochloride salt [20]. Detailed pharmacological investigations showed that this compound owes its antidepressant action to the inhibition of reuptake of dopamine and norepinephrine from the synaptic cleft. 

A method for synthesizing 1,3,4,5-tetrahydrobenzo[af)indoles 171 from 2-aminotetralins 168, which were first formylated by formic acid or N-formylimidazole, was described. The 2-formyltetralins thus formed were... 

Michael reactions. A synthesis of the 2-aminotetralin (4) uses 1 as the Michael... 

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