Diouf, O.
Depreux, P.
Chavatte, P
Poupaert, Jacques
[UCL]
The indole derivative GR 113808 is currently used as the reference Ligand for labelling the 5-HT4 serotoninergic receptors. Previous works in our laboratories established the bioisosteric equivalency of the indole heterocycle and naphthalene in a series of melatonin receptor ligands. Based on this knowledge we designed new analogues of GR 113808 by introducing two bioisosteric modifications: firstly, the indole ring was replaced by a naphthalene one and secondly, the ester linkage was replaced by an amide group. Compound 8 emerged within this novel series as it displayed high and selective affinity at 5-HT4 receptors (Ki 5-HT4 = 6 nM, Ki 5-HT3 = 100 nM, Ki values at other 5-HT receptors were higher than 1 000 nM). Compound 8 is currently undergoing further pharmacological evaluation. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
Bibliographic reference |
Diouf, O. ; Depreux, P. ; Chavatte, P ; Poupaert, Jacques. Synthesis and preliminary pharmacological results on new naphthalene derivatives as 5-HT4 receptor ligands. In: European Journal of Medicinal Chemistry, Vol. 35, no. 7-8, p. 699-706 (2000) |
Permanent URL |
http://hdl.handle.net/2078.1/43366 |