Centrally acting emetics. 6. Derivatives of .beta.-naphthylamine and 2-indanamine

Cannon, Joseph G.; Kim, J C; Aleem, Mohd

doi:10.1021/jm00274a003

Cited by 52 publications

(24 citation statements)

References 3 publications

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“…Previously, the addition of N-dialkyl groups to restricted analogs of dopamine has been shown to increase their potency on behavioral test for dopamine agonist activity (29)(30)(31)(32). Therefore, it was not surprising that the addition of N-dimethyl groups to the geometric isomers of 2-amino-1-(3,4-dihydroxyphenyl)cyclobutane increased their affinity for the [3H]dopamine binding site.…”

Section: Discussionmentioning

confidence: 99%

Conformation of dopamine at the dopamine receptor.

Komiskey¹,

Bossart²,

Miller³

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

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Tritiated dopamine was used to label the dopamine receptor in membranes isolated from the rat corpus striatum. Scatchard analysis of displacement of [3Hldopamine by nonradioactive dopamine indicated the presence of two binding sites. The similarities in affinity, capacity, and drug specificity of the high-affinity site in the striatal membranes from rat and the binding site in the membranes from the calf caudate nucleus suggest that [3Hjdopamine labels the same site in both species. In order to determine what conformation of dopamine is preferred at the dopamine receptor site, conformationally restricted analogs of dopamine-namely, the cis and trans 2-amino-1(3,4-dihydroxyphenyl)cyclobutane hydrochlorides-were tested for their affinity to the receptor. Compared to the cis conformation, the trans-restricted analogs had more affinity for the receptor site, indicating that dopamine probably interacts with the receptor in the trans conformation.There is considerable interest in the relationship between conformation of neurotransmitters at their receptors and biological activity (1, 2). The putative neurotransmitter dopamine is probably involved in parkinsonism (3), Huntington chorea (4), drug-induced dyskinesia (5, 6), schizophrenia (7), and manic depressive psychosis (8,9). The preferred conformation of dopamine in the solid state is the trans extended form, and in solution it exists primarily in the trans and gauche conformations with the trans form being slightly predominant (10, 11).However, it is realized that the preferred conformation of dopamine in the dopamine-receptor complex need not be the same as that in solution or in the solid state (11, 2). Nevertheless, investigations with dopamine-sensitive adenylate cyclase support the idea that the trans extended form of dopamine interacts with the dopamine receptor. Among the semirigid analogs of dopamine, the compounds with the greatest potency are those with the ethylamine side chain of dopamine in the fully extended form, as in apomorphine and 2-amino-6,7-dihydroxytetralin (12)(13)(14)(15)(16). On the other hand, there are significant differences indrugaffinity,subcellular localization, and ontogenetic developmental pattern between the dopamine receptor recognition site and adenylate cyclase (17)(18)(19)(20). Thus, the significance of the dopamine-sensitive adenylate cyclase data in relation to dopamine-mediated behaviors is not known.Apomorphine and 2-amino-6,7-dihydroxytetralin have an affinity for the dopamine receptor binding site as great or greater than that of dopamine (21). This affinity, however, may not be due to these compounds having the dopamine moiety in a fully extended form, because no binding study has been carried out comparing the affinity of isomeric compounds that possess a cis and trans relationship between the catechol and amino groups found in dopamine. Therefore, to determine the preferred conformation of dopamine at its receptor site, we Ci/mmol, New England Nuclear) which was added in 100 gl of 0.1% ascorbic acid, 1.8 ml of...

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Section: Discussionmentioning

confidence: 99%

Conformation of dopamine at the dopamine receptor.

Komiskey¹,

Bossart²,

Miller³

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

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“…1). Previous studies with certain derivatives of A-5,6-DTN indicated that they exert dopamine-like activity in the central nervous system, because they are potent emetic agents and produce gnawing behavior in mice (8,9). Some of these analogs have also been shown to produce typical (32-adrenergic actions (10).…”

Section: Dopamine Can Cause Vasodilation By Several Mechanisms (1)mentioning

confidence: 99%

Conformational requirements for dopamine-induced vasodilation.

Volkman¹,

Kohli²,

Goldberg³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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ABSIRACT The availability of a series of semi-rigid analogs of dopamine and epinine has made it possible to investigate the conformational requirements for action on dopamine and 2-adrenergic vascular receptors. The analogs were screened for dopamine-agonist action by intra-arterial injections into the renal vascular bed and for P2-adrenergic activity by similar injections into the femoral vascular bed in dogs pretreated with phenoxybenzamine. 2-Amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene and its N-methyl derivative (analogous to the trans P rotamer of dopamine) exhibited pronounced dopamine-agonist activity and minimal 02-adrenergic activity. In contrast, the semi-rigid analog of the trans a rotamer of dopamine (2-amino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene; A-5,6-DTN) and its N-methyl derivative exerted pronounced #2-adrenergic activity but were inactive as dopamine agonists.6,7-Dihydroxytetrahydroisoquinoline,a semirigid analog of the cis P rotamer of dopamine, did not produce renal vasodilation. These results indicate that a conformation of dopamine similar to that found in A-6,7-DTN is required for dopamine-vascular activity, while the conformation found in A-5,6-DTN is preferred for interaction with #2-adrenergic receptors. Dopamine can cause vasodilation by several mechanisms (1).Vasodilation can be induced directly by action on 32radrenergic or dopamine vascular receptors (2) and indirectly by action on receptors in autonomic ganglia (3, 4) and postganglionic sympathetic nerves (5, 6). Because the dopamine molecule is flexible and can assume a variety of conformations, it has not been possible to determine whether a specific conformation is required for each of these diverse actions. A possible approach to this problem has been provided recently by the demonstration that a semi-rigid analog of dopamine, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (A-6,7-DTN), met all the criteria of a dopamine agonist in the canine renal and mesenteric vascular beds (7). Because the side chain of the dopamine moiety contained within A-6,7-DTN is fixed in a fully extended position with the amino group trans to the phenyl ring, these results suggested that this conformation of dopamine (trans ,B rotamer) may be required for activation of dopamine receptors. However, dopamine can exist in yet another trans conformation (trans a rotamer) as in 2-amino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene , in which the phenyl ring has undergone a 1800 rotation about the phenyl-C-1 bond (see Fig. 1). Previous studies with certain derivatives of A-5,6-DTN indicated that they exert dopamine-like activity in the central nervous system, because they are potent emetic agents and produce gnawing behavior in mice (8, 9). Some of these analogs have also been shown to produce typical (32-adrenergic actions (10).Accordingly, we have compared the relative ,32-adrenergicThe costs of publication of this article were defrayed in part by the payment of page charges from funds made available to support the research which is the su...

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“…[1][2][3] It serves as the starting material for the preparation of several drugs such as the 2-aminotetralins, [4][5][6][7][8] which act as dopaminergic agonists in the treatment of Parkinson's disease. 9 It is also used as the key intermediate in the synthesis of many other naphthalene derivatives. 10, 11 2,6-Dihydroxynaphthalene (1) has been prepared by two general methods.…”

Section: 6-dihydroxynaphthalenementioning

confidence: 99%

A Convenient and Efficient Synthesis of 2,6-Dihydroxynaphthalene

Cui

2012

Journal of Chemical Research

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A convenient synthesis of 2,6-dihydroxynaphthalene from 6-bromo-2-naphthol has been achieved with high overall yield (52%) and good purity (95.7%) based on the conversion of 6-(methoxymethoxy)-2-naphthaldehyde to 6-(methoxymethoxy)-2-naphthol formate by a Baeyer-Villiger oxidation-rearrangement. Compared with the reported methods, the reaction conditions are milder and the work-up of each step is much simpler. Moreover, 6-bromo-2naphthol as the starting material for the synthesis is readily available. Scheme 1 (a) NaH, MOMCl, DMF; 93%. (b) n-BuLi, THF, -78 °C; DMF; 81%. (c) m-CPBA, CH 2 Cl 2 , 10 °C; 72%. (d) HCl, MeOH-H 2 O; 95%.

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Centrally acting emetics. 6. Derivatives of .beta.-naphthylamine and 2-indanamine

Cited by 52 publications

References 3 publications

Conformation of dopamine at the dopamine receptor.

Conformation of dopamine at the dopamine receptor.

Conformational requirements for dopamine-induced vasodilation.

A Convenient and Efficient Synthesis of 2,6-Dihydroxynaphthalene

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