Premium
Synthesis and Preliminary Pharmacological Investigation of New N ‐Substituted‐ N ‐[ω‐(ω‐phenoxy‐alkylpiperazin‐1‐yl)alkyl]guanidines as Non‐Imidazole Histamine H 3 Antagonists
Author(s) -
Staszewski Marek,
Walczyński Krzysztof
Publication year - 2012
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.201100428
Subject(s) - histamine , imidazole , guanidine , chemistry , stereochemistry , in vitro , histamine receptor , histamine h2 receptor , biological activity , receptor , alkyl , chemical synthesis , medicinal chemistry , antagonist , pharmacology , biochemistry , organic chemistry , biology
Novel, potent non‐imidazole histamine H 3 receptor antagonists were prepared. Detailed structure–activity studies revealed that N ‐(4‐trifluoromethylbenzyl)‐ N ‐[4‐(7‐phenoxyheptylpiperazin‐1‐yl)butyl]guanidine (pA 2 = 8.49 ± 0.05), 1h , and N ‐(4‐nitrobenzyl)‐ N ‐[4‐(7‐phenoxyheptylpiperazin‐1‐yl)butyl]guanidine (pA 2 = 8.43 ± 0.05), 1l , exhibit high affinity for the H 3 histamine receptor. The most potent antagonists in this series, 1e , 1h , and 1l , were also in vitro tested as H 1 receptor antagonists, showing weak H 1 ‐antagonistic activity with pA 2 = 6.70 ± 0.09, pA 2 = 6.46 ± 0.09, and pA 2 = 6.65 ± 0.11, respectively.