title: 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.
abstract: 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.
authors.affiliation: Department of Synthesis and Technology of Drugs, Medical University, Łódź, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Staszewski
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Walczyński
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D054828:Histamine H3 Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D011969:Receptors, Histamine H1 / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D006146:Guanidines; D054828:Histamine H3 Antagonists; C576798:N-(4-nitrobenzyl)-N-(4-(7-phenoxyheptylpiperazin-1-yl)butyl)guanidine; C576797:N-(4-trifluoromethylbenzyl)-N-(4-(7-phenoxyheptylpiperazin-1-yl)butyl)guanidine; D010879:Piperazines; D011969:Receptors, Histamine H1; D018100:Receptors, Histamine H3