6-Aminotetralin

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. 

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. 

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. 

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... 

An interesting comparison can be made looking at the a- and (5-tetralin derivatives entries—15/16 and —17 in Table 1 which can be regarded as cyclic confor-mationally constrained analogues of phenylglycine and phenylalanine. In an interesting study, 6-hydroxy-2-aminotetralin-2-carboxylic acid 12 (Hat) has been incorporated as a conformationally constrained tyrosine analogue into S-opioid receptor selective tetrapeptides.114 15 Whereas entry 15, the (S)-a-tetralin deriva-... 

Dihydroxy-2- aminotetralin (ADTN) dimethyl ADTN acti ve inactive... 

Dihydroxy-2- aminotetralin primary amine acti ve i nacti ve... 

Some of the earliest and most complete efforts at structural dissection have been carried through by Cannon and his co-workers at the University of Iowa. These studies were initially directed toward elucidation of the pharmacophoric element within the structure of the emetic agent apomorphine, I. The suggestion by Pinder et al. (2) that the 5,6-dihydroxy-2-aminotetralin fragment was the active moiety was followed in short order by the report of Cannon et al. (3) that the N,N-dimethyl derivative ("M-7") II was a potent emetic in the dog. Additional pharmacology on M-7 provided by Long et al. (4) further illustrated the similarity between I and II. Both... 

Until very recently apomorphine (APO) was the only important chiral DA agonist whose enantiomers had been studied. The only congeneric groups of resolved agonists to be reported subsequently were 2-aminotetralins 1, 2 ). The present enantiomer study of the SK F 38393 series thus provides welcome new data for stereochemical definition of DA receptors. Moreover, the previous studies employed rather narrow choices of pharmacological models. The broader range of models presented here is therefore particularly helpful. 

Holmberg P, Sohn D, Leideborg R, et al. Novel 2-aminotetralin and 3-aminochro-man derivatives as selective serotonin 5-HT7 receptor agonists and antagonists. J Med Chem 2004 47 3927-3930. 

Mosberg and co-workers utilized a similar type of approach for constraining the flexibility of Tyr in JOM-13 [69]. In an effort to better determine the binding conformation of the Tyr1 residue, a series of conformationally constrained analogues of Tyr (FlO-Tic 7-hydroxy-1,2,3,4-tetrahydroisoquin-oline-3- carboxylic acid Flai 6-hydroxy-2-aminoindan-2-carboxylic acid Hat 6-hydroxy-2-aminotetralin-2-carboxylic acid, and c-Hpp and t-Hpp ... 

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 59 8155-8159. 

Herroelen L, Debacker JP, Wilczak N, Flamez A, Vauquelin G, De Keyser J (1994) Autoradiographic distribution of D3-type dopamine receptors in human brain using [3H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin. Brain Res 648 222-228. 

Wallace DR, Booze RM (1995) Identification of D3 and sigma receptors in the rat striatum and nucleus accumbens using (+/—)-7-hydroxy-N,N-Di-n-[3H]propyl-2-aminotetralin and carbetapentane. J Neurochem 64 700-710. 

The 2-aminotetralin skeleton has attracted several groups as a basis for potential analgesics. Martin ef a/.(44) succeeded in obtaining several derivatives... 

Cl1 HI202 ethyl trans-cinnamate 4192-77-2 544.65 48.190 1.2 21973 O11H13N02 2-aminotetralin-2-carboxylic acid 74444-77-2 576.15 51.247 2... 

Chart 1.3 Gauche conformation of dopamine (1) and the two retainers of the extended conformation of dopamine (1 a-conformer and 1 (3-conformer), and the corresponding 2-aminotetralins S-(-)-5-OH-DPAT (9) and R-(+)-7-OH-DPAT (10). 

The rigidification of the dopamine molecule led to a number of dopamine receptor agonists in which the dopamine molecule, with its phenylethylamine moiety, is readily recognisable. In these dopamine agonists the amine moiety is either a part of a cyclic system, e.g. benzo[/]quinolines, naphthoxazines, and benzopyranoxazines, or an exocyclic amine, e.g. 2-aminotetralins and 2-aminoindans (Chart 1.5). 

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