2-Aminotetralins and DA D2, D3, and D4 Receptors
J ournal of Medicinal Chemistry, 1996, Vol. 39, No. 21 4237
(6) Cannon, J . G.; Lee, T.; Goldman, H. D.; Costall, B.; Naylor, R.
J . Cerebral Dopamine Agonist Properties of Some 2-Amino-
tetralin Derivatives after Peripheral and Intracerebral Admin-
istration J . Med. Chem. 1977, 20, 1111-1116.
(20) Cornforth, J . W.; Cornforth, R. H.; Robinson, R. The Preparation
of â-Tetralone From â-Naphtol and Some Analogous Transfor-
mations. J . Chem. Soc. 1942, 689-691.
(21) (a) Sibley, D. R.; Delean, A.; Creese, I. Anterior Pituitary
Dopamine Receptors: Demonstration of Interconvertible High
an Low Affinity States of the D2 Dopamine Receptor. J . Biol.
Chem. 1982, 257, 6351-6361. (b) Urwyler, S.; Markstein, R.
Identification of Dopamine “D3” and “D4” Binding Sites, Labelled
with 3H-2-Amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene,
as High Agonist Affinity States of the D1 and D2 Dopamine
Receptors, Respectively. J . Neurochem. 1986, 46, 1058-1067.
(c) Seeman, P.; Watanabe, M.; Grigoriadis, D.; Tedesco, J . L.;
George, S. R.; Svensson, U.; Nilsson, J . L. G.; Neumeyer, J . L.
Dopamine D-2 Receptor Binding Sites for Agonists: A Tetra-
hedral Model. Mol. Pharmacol. 1985, 28, 391-399. (d) Hamblin,
M. W.; Leff, S. E.; Creese, I. Interactions of Agonists with D2
Dopamine Receptors: Evidence for a Single Receptor Population
Existing in Multiple Agonist Affinity-States in Rat Striatal
Membranes. Biochem. Pharmacol. 1984, 33, 877-887.
(22) (a) Chio, C. L.; Lajiness, M. E.; Huff, R. M.; Activation of
Heterologously Expressed D3 Dopamine Receptors: Comparison
with D2 Dopamine Receptors. Mol. Pharmacol. 1994, 45, 51-
60. (b) Burris, K. D.; Filtz, T. M.; Chumpradit, S.; Kung, M.-P.;
Foulon, C.; Hensler, J . G.; Kung, H. K.; Molinoff, P. B. Charac-
terization of [125I](R)-Trans-7-hydroxy-2-[N-propyl-N-(3′-iodo-2′-
propenyl)amino]tetralin Binding to Dopamine D3 Receptors in
Rat Olfactory Tubercle. J . Pharmacol. Exp. Ther. 1994, 268,
935-942.
(23) Chen, C.; Okayama, H. High-efficiency Transformation of Mam-
malian Cells by Plasmid DNA. Mol. Cell Biol. 1987, 7, 2745-
2752.
(24) MacKenzie, R. G.; VanLeeuwen, D.; Pugsley, T. A.; Shih, Y.-H.;
DeMattos, S.; Tang, L.; Todd, R. D.; O’Malley, K. L. Character-
ization of the Human D3 Receptor Expressed in Transfected Cell
Lines. Eur. J . Pharmacol., Mol. Pharmacol. Sect. 1994, 266, 79-
85.
(25) (a) Shih, Y. H.; Pugsley, T. A.; Taylor, M.; Chung, F. Z. The
Expression and Functional Characterization of Human Dop-
amine D4.2 Receptor in CHO K1 Cells. Soc. Neurosci. 1995, 21,
620. (b) Shih, Y. H.; Chung, F. Z.; Pugsley, T. A. Cloning,
Expression and Characterization of a Human D4.2 Receptor
(CHO K1 Cells) and Various D4.2/D2L Chimeras (COS-7 Cells).
Methods Findings Exp. Clin. Pharmacol. (submitted for publica-
tion).
(26) Cheng, Y.-C.; Prusoff, W. H. Relationship Between the Inhibition
Constant (Ki) and the Concentration of Inhibitor Which Causes
50% Inhibition (IC50) of an Enzymatic Reaction. Biochem.
Pharmacol. 1973, 22, 3099-3108.
(27) J ansen, J . M.; Den Daas, I.; Rollema, H.; Swart, P. J .; Tepper,
P.; De Vries, J . B.; Horn, A. S. Pharmacological Profile of Non-
hydroxylated and Ether Derivatives of the Potent D2-Selective
Agonist N-0437. Naunyn-Schmiedeberg’s Arch. Pharmacol. 1991,
343, 134-142.
(28) Horn, A. S. U.S. Patent No. 4,564,628, J anuary 14, 1986.
(29) Ames, D. E.; Evans, D.; Grey, T. F.; Islip, P. J .; Richards, K. E.
The Synthesis of Alkoxy-1,2,3,4-tetrahydronaphthalene Deriva-
tives. Part I. 2-Amino-, Alkylamino-, and Dialkylamino-deriva-
tives. J . Chem. Soc. 1965, 2636-2641.
(30) Windaus, A. U¨ ber einige Derivate des ac.-Tetrahydro-â-naph-
tylamins. (About Some Derivatives of Acetyl-tetrahydro-â-
naphthylamine.) Ber. 1924, 57, 1731-1739.
(31) Beart, P. M.; Cook, C. J .; Cincotta, M.; De Vries, D. J .; Tepper,
P.; Dijkstra, D.; Horn, A. S. Radioreceptor Binding Reveals the
Potencies of N,N-disubstituted 2-aminotetralins as D2 Dopamine
Agonists. Naunyn-Schmiedeberg’s Arch. Pharmacol. 1987, 336,
487-493.
(7) Seiler, M. P.; Markstein, R. Further Characterization of Struc-
tural Requirements for Agonists at the Striatal Dopamine D-1
Receptor. Mol. Pharmacol. 1982, 22, 281-289.
(8) Hacksell, U.; Svensson, U.; Nilsson, J . L. G.; Hjorth, S.; Carlsson,
A.; Wikstro¨m, H.; Lindberg, P.; Sanchez, D. N-Alkylated
2-Aminotetralins: Central Dopamine-Receptor Stimulating Ac-
tivity. J . Med. Chem. 1979, 22, 1469-1475.
(9) Seiler, M. P.; Stoll A. P.; Closse, A.; Frick, W.; J aton, A.; Vigouret,
J .-M. Structure-Activity Relationships of Dopaminergic 5-Hy-
droxy-2-aminotetralin Derivatives with Functionalized N-Alkyl
Substituents. J . Med. Chem. 1986, 29, 912-917.
(10) Wikstro¨m, H.; Andersson, B.; Sanchez, D.; Lindberg, P.; Arvids-
son, L.-E.; J ohansson, A. M.; Nilsson, J . L. G.; Svensson, K.;
Hjorth, S.; Carlsson, A. Resolved Monophenolic 2-Aminotetralins
and 1,2,3,4,4a,5,6,10b-Octahydrobenzo[f]quinolines: Structural
and Stereochemical Considerations for Centrally Acting Pre- and
Postsynaptic Dopamine-Receptor Agonists. J . Med. Chem. 1985,
28, 215-225.
(11) Horn, A. S.; Tepper, P.; Van Der Weide, J .; Watanabe, M.;
Grigoriadis, D.; Seeman, P. Synthesis and Radioreceptor Binding
Activity of N-0437, a New, Extremely Potent and Selective D2
Dopamine Receptor Agonist. Pharm. Weekbl., Sci. Ed. 1985, 7,
208-211.
(12) Seiler, M. P.; Markstein, R. Further Characterization of Struc-
tural Requirements for Agonists at the Striatal Dopamine D2
Receptor and a Comparison with Those at the Striatal Dopamine
D1 Receptor. Mol. Pharmacol. 1984, 26, 452-457.
(13) (a) Le´vesque, D.; Diaz, J .; Pilon, C.; Martres, M.-P.; Giros, B.;
Souil, E.; Schott, D; Morgat, J .-L.; Schwartz, J .-C.; Sokoloff, P.
Identification, Characterization, and Localization of the Dop-
amine D3 Receptor in Rat Brain Using [3H]-7-hydroxy-N,N-di-
n-propyl-2-aminotetralin. Proc. Natl. Acad. Sci. U.S.A. 1992, 89,
8155-8159. (b) Damsma, G.; Bottema, T.; Westerink, B. H. C.;
Tepper, P. G.; Dijkstra, D.; Pugsley, T. A.; MacKenzie, R. G.;
Heffner, T. G.; Wikstro¨m, H. Pharmacological Aspects of R-(+)-
7-OH-DPAT, a Putative Dopamine D3 Receptor Ligand. Eur. J .
Pharmacol. 1993, 249, R9-R10.
(14) Sokoloff, P.; Giros, B.; Martres, M.-P.; Bouthenet, M.-L.; Schwartz,
J .-C. Molecular Cloning and Characterization of a Novel Dop-
amine Receptor (D3) as a Target for Neuroleptics. Nature 1990,
347, 146-151.
(15) Van Tol, H. H.; Bunzow, J . R.; Guan, H. C.; Sunahara, R. K.;
Seeman, P; Niznik, H. B.; Civelli, O. Cloning of the Gene for a
Human Dopamine D4 Receptor with High Affinity for the
Antipsychotic Clozapine. Nature 1991, 350, 610-614.
(16) (a) Seeman, P.; Guan, H.-C.; Van Tol, H. H. M. Dopamine D4
Receptors Elevated in Schizophrenia. Nature 1993, 365, 441-
445. (b) Seeman, P.; Guan, H.-C.; Van Tol, H. H. M. Schizophre-
nia: Elevation of Dopamine D4-Like Sites, Using [3H]-
Nemonapride and [125I]Epidepride. Eur. J . Pharmacol. 1995,
286, R3-R5.
(17) (a) Reynolds, G. P.; Mason, S. L. Are Striatal Dopamine D4
Receptors Increased in Schizophrenia? J . Neurochem. 1994, 63,
1576-1577. (b) Reynolds, G. P.; Mason, S. L. Absence of
Detectable Striatal Dopamine D4 Receptors in Drug-treated
Schizophrenia. Eur. J . Pharmacol. 1995, R5-R6.
(18) Akunne, H. C.; Towers, P; Ellis, G. J .; Dijkstra, D.; Wikstro¨m,
H.; Heffner, T. G.; Wise, L. D.; Pugsley, T. A. Characterization
of Binding of [3H]PD 128907, a Selective Dopamine D3 Receptor
Agonist Ligand, to CHO-K1 Cells. Life Sci. 1995, 57, 1401-1410.
(19) Pugsley, T. A.; Davis, M. D.; Akunne, H. C.; MacKenzie, R. G.;
Shih, Y. H.; Damsma, G.; Wikstro¨m, H.; Whetzel, S. Z.; Georgic,
L. M.; Cooke, L. W.; Demattos, S. B.; Corbin, A. E.; Glase, S. A.;
Wise, L. D.; Dijkstra, D.; Heffner, T. G. Neurochemical and
Functional Characterization of the Preferentially Selective
Dopamine D3 Agonist PD 128907. J . Pharmacol. Exp. Ther.
1995, 275, 1355-1366.
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