Volume 335, Issue 8 pp. 367-373

Full Paper

Dopamine/Serotonin Receptor Ligands, Part III [1]: Synthesis and Biological Activities of 7, 7′—Alkylene-bis-6, 7, 8, 9, 14, 15-hexahydro-5H-benz[d]indolo[2, 3-g]azecines — Application of the Bivalent Ligand Approach to a Novel Type of Dopamine Receptor Antagonist

Ashraf H. Abadi,

Ashraf H. Abadi

Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, University of Jena, Jena, Germany

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Stefan Lankow,

Stefan Lankow

Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, University of Jena, Jena, Germany

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Barbara Hoefgen,

Barbara Hoefgen

Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, University of Jena, Jena, Germany

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Michael Decker,

Michael Decker

Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, University of Jena, Jena, Germany

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Matthias U. Kassack,

Matthias U. Kassack

Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, University of Jena, Jena, Germany

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Jochen Lehmann,

Corresponding Author

Jochen Lehmann

[email protected]

Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, University of Jena, Jena, Germany

Institute of Pharmacy, University of Jena, Philosophenweg 14, D-07743 Jena, Germany. Phone. +49 3641 949803, Fax: +49 3641 949802Search for more papers by this author

Ashraf H. Abadi,

Ashraf H. Abadi

Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, University of Jena, Jena, Germany

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Stefan Lankow,

Stefan Lankow

Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, University of Jena, Jena, Germany

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Barbara Hoefgen,

Barbara Hoefgen

Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, University of Jena, Jena, Germany

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Michael Decker,

Michael Decker

Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, University of Jena, Jena, Germany

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Matthias U. Kassack,

Matthias U. Kassack

Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, University of Jena, Jena, Germany

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Jochen Lehmann,

Corresponding Author

Jochen Lehmann

[email protected]

Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, University of Jena, Jena, Germany

Institute of Pharmacy, University of Jena, Philosophenweg 14, D-07743 Jena, Germany. Phone. +49 3641 949803, Fax: +49 3641 949802Search for more papers by this author

First published: 21 October 2002

https://doi.org/10.1002/1521-4184(200211)335:8<367::AID-ARDP367>3.0.CO;2-C

Citations: 19

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Abstract

A series of 7, 7′—alkylene-bridged dimers(7a—e) of the benz [d]indolo[3, 2-f]azecine derivative LE300 was synthesized. Affinity and functional activity at dopamine D₁ and D₂ receptors were estimated by radioligand binding and a functional Ca²⁺ assay. All the new bivalent ligands showed significant binding affinities to both D₁ and D₂ receptorswith an optimal distance between the two monomeric recognition unitsof 6 methylene moieties. The D₁/D₂-selectivity pattern was dependent on the spacer length. No (7a, b) or only moderate (7c—e) functional activity wasdetected for all bivalent compounds by measuring the inhibition of agonist-induced increase in intracellular Ca²⁺.

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Volume335, Issue8

November 2002

Pages 367-373

Dopamine/Serotonin Receptor Ligands, Part III [1]: Synthesis and Biological Activities of 7, 7′—Alkylene-bis-6, 7, 8, 9, 14, 15-hexahydro-5H-benz[d]indolo[2, 3-g]azecines — Application of the Bivalent Ligand Approach to a Novel Type of Dopamine Receptor Antagonist

Abstract

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Dopamine/Serotonin Receptor Ligands, Part III [1]: Synthesis and Biological Activities of 7, 7′—Alkylene-bis-6, 7, 8, 9, 14, 15-hexahydro-5H-benz[d]indolo[2, 3-g]azecines — Application of the Bivalent Ligand Approach to a Novel Type of Dopamine Receptor Antagonist

Abstract

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