| abstract |
A class of 1-[3-(1H-indol-3-yl)propyl]-4-(2-phenylethyl)piperazine derivatives, substituted at the 5-position of the indole nucleus by a five-membered heteroaromatic moiety, on one or other of the ethylene carbon atoms of the phenethyl moiety by halogen, trifluoromethyl, alkyl, hydroxyalkyl or alkoxyalkyl, and optionally on the phenyl ring of the phenethyl moiety by halogen, trifluoromethyl, alkoxy or an oxazolidinone group and optionally by one or two further substituents, are selective agonists of 5-HT 1 -like receptors, being potent agonists of the human 5-HT 1D α receptor subtype whilst possessing at least a 10-fold selective affinity for the 5-HT 1D α receptor subtype relative to the 5-HT 1D β subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT 1D receptors is indicated, whilst eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT 1D receptor agonists. |