753022-84-3Relevant academic research and scientific papers
Structure-affinity studies for a novel series of homochiral naphtho and tetrahydronaphtho analogues of α1 antagonist WB-4101
Bolchi, Cristiano,Catalano, Paolo,Fumagalli, Laura,Gobbi, Marco,Pallavicini, Marco,Pedretti, Alessandro,Villa, Luigi,Vistoli, Giulio,Valoti, Ermanno
, p. 4937 - 4951 (2007/10/03)
A number of enantiomeric pairs of naphthodioxane, tetrahydronaphthodioxane and naphthoxy analogues of WB-4101 (1) were designed and synthesized in order to improve the selectivity profile of the parent compound, hopefully in favour of the α1a-AR with respect to the other two α1 subtypes and the 5-HT1A receptor. The new compounds 2-8 and, in addition, the two enantiomers of 1 were tested in binding assays on the α1a-AR, α1b-AR, α1d-AR, and the 5-HT1A receptor. Two of them, namely the naphtho- and tetrahydronaphthodioxane derivatives (S)-2 and (S)-3, showed lower, but significantly more specific α1a affinity than (S)-1, while the two enantiomers of the 2-methoxy-1-naphthoxy analogue 6 maintained most of the very high α1a affinity of (S)-1 and its α1a versus α1b selectivity slightly increasing the α1a/α1d and α1a/5HT 1A affinity ratios. The SAR data were evaluated in the light of known α1 subtype pharmacophores and of the α1a-AR binding mode of WB-4101 resultant from literature mutagenesis studies disclosing some interesting consonances with these models.
