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Residues at the Indole‐ NH of LE300 Modulate Affinities and Selectivities for Dopamine Receptors
Author(s) -
Robaa Dina,
Kretschmer Robert,
Siol Oliver,
AbulAzm Shams ElDin,
ElKhawass ElSayeda,
Lehmann Jochen,
Enzensperger Christoph
Publication year - 2011
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201000121
Subject(s) - affinities , indole test , chemistry , receptor , dopamine receptor , dopamine , stereochemistry , binding affinities , combinatorial chemistry , biochemistry , neuroscience , biology
To further investigate SAR in the class of azecine‐type dopamine receptor antagonists, we synthesized a series of derivatives, substituted at the indole‐ NH of the lead compound LE300 by different alkyl chains in addition to phenylpropyl, allyl, propargyl, and acetyl residues. The affinities of the target compounds for all human dopamine receptors (D 1 –D 5 ) were investigated by radioligand binding assay and their functionality by a calcium assay. Both the affinities and selectivities for the dopamine receptors were found to be affected by the nature of the substituent. The N 14‐methylated derivative displayed the highest affinities for all D‐receptors. In general, the affinities decreased with increasing chain length of the N‐alkyl. Different substituents, partly led to altered affinity, and selectivity profile when compared with our lead LE300.