Development of Novel 1,2,3,4-Tetrahydroisoquinoline Derivatives and Closely Related Compounds as Potent and Selective Dopamine D3 Receptor Ligands
| Autor: | Pierre Sokoloff, Ulrich R. Mach, Sandrine Ferry, Jean-Charles Schwartz, Holger Stark, Sylvie Perachon, Camille G. Wermuth, Anneke E. Hackling |
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| Rok vydání: | 2004 |
| Předmět: |
Stereochemistry
CHO Cells Ligands Biochemistry Partial agonist Piperazines chemistry.chemical_compound Dopamine receptor D3 Dopamine Cricetinae Tetrahydroisoquinolines Dopamine receptor D2 medicine Radioligand Animals Humans Moiety Molecular Biology Molecular Structure Receptors Dopamine D2 Chemistry Tetrahydroisoquinoline Organic Chemistry Receptors Dopamine D3 BP-897 Molecular Medicine medicine.drug |
| Zdroj: | ChemBioChem. 5:508-518 |
| ISSN: | 1439-4227 |
| DOI: | 10.1002/cbic.200300784 |
| Popis: | Based on N-alkylated 1,2,3,4-tetrahydroisoquinoline derivatives, which are structurally related to the partial agonist BP 897, a series of novel, selective dopamine D3 receptor antagonists has been synthesised. Derivatisation included changes in the arylamide moiety and the tetrahydroisoquinoline substructure leading to compounds with markedly improved selectivities and affinities in the low nanomolar concentration range. From the 55 structures presented here, (E)-3-(4-iodophenyl)-N-(4-(1,2,3,4-tetrahydroisoquinolin-2-yl)butyl)acrylamide (51) has high affinity (Ki(hD3)=12 nM) and a 123-fold preference for the D3 receptor relative to the D2 receptor subtype. Its pharmacological profile offers the prospect of a novel radioligand as a tool for various dopamine D3-receptor-related in vitro and in vivo investigations. |
| Databáze: | OpenAIRE |
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