1-Phenoxyalkyl-4-[(N,N-disubstitutedamino)alkyl]piperazine derivatives as non-imidazole histamine H3-antagonists

• DOI: 10.1007/s00044-012-0090-2
• Publication Date: 2012-06-11T01:05:06Z
• Authors: Marek Staszewski; Krzysztof Walczyński
• Keywords: 0303 health sciences; 03 medical and health sciences; 3. Good health

In this study, a series of 1-phenoxyalkyl-4-[(N,N-disubstitutedamino)alkyl]piperazine derivatives has been prepared and in vitro tested as H3-receptor antagonists (electrically evoked contraction of the guinea pig jejunum). All compounds investigated show moderate in vitro affinities. The most potent antagonists in this series are the compounds 9b, 1b, 1f, and 1l, which exhibit, independently of the substituent at the end of -N- moiety, almost the same level of affinity (pA 2 = 7.18, pA 2 = 7.27, pA 2 = 7.13, pA 2 = 7.12, respectively). The histaminergic H1 antagonism of the aforementioned four products was established on the isolated guinea pig ileum by conventional methods; the pA 2 values were compared with the potency of pyrilamine. None of them shows any H1-antagonistic activity (pA 2 < 4; for pyrilamine pA 2 = 9.35).