239482-65-6Relevant academic research and scientific papers
Design, synthesis, and structure-activity relationships of novel non- imidazole histamine H3 receptor antagonists
Linney, Ian D.,Buck, Ildiko M.,Harper, Elaine A.,Kalindjian, S. Barret,Pether, Michael J.,Shankley, Nigel P.,Watt, Gillian F.,Wright, Paul T.
, p. 2362 - 2370 (2000)
Novel, potent, and selective non-imidazole histamine H3 receptor antagonists have been prepared based on the low-affinity ligand dimaprit (pK(I) 7.32 ± 0.12, pK(B) 5.93 ± 0.17). Detailed structure-activity studies have revealed that N-(4-chlorobenzyl)-N-(6-pyrrolidin-1-ylhexyl)guanidine (pK(I) 8.38 ± 0.21, pK(B) 8.39 ± 0.13), 30, and N-(4-chlorobenzyl)-N-(7- pyrrolidin-1-ylheptyl)guanidine (pK(I) 8.78 ± 0.12, pK(B) 8.38 ± 0.10), 31, exhibit high affinity for the histamine H3 receptor. Antagonists 30 and 31 demonstrate significant selectivity over the other histamine, H1 and H2, receptor subtypes and a 100-fold selectivity in the σ1 binding assay. Compounds 30 and 31 are the most potent, selective non-imidazole histamine H3 receptor antagonists reported in the literature to date.
HISTAMINE H3 RECEPTOR LIGANDS
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Page 10, (2010/02/05)
Compounds of formula (I) (and pharmaceutically acceptable salts thereof) are histamine H3 receptor ligands. A in the formula represents (CH2)m, m being from 1 to 3; B is (CH2)n, n being from 1 to 3; x is from 0 to 2; Ris C1 to C10 hydrocarbyl, in which up to 2 carbon atoms may be replaced by O, S or N; and up to 2 hydrogen atoms may be replaced by halogen; Ris H or C1 to C15 hydrocarbyl, in which up to 3 carbon atoms may be replaced by O, S or N, and up to 3 hydrogen atoms may be replaced by halogen; Ris absent when -Y-Z-R2 is attached to W, or is H or C1 to C7 hydrocarbyl when -Y-Z-Ris not attached to W; W is nitrogen; X is -CH2-, -O- or -NR-, Rbeing H or C1 to C3 alkyl; Y replaces a hydrogen atom on any of A, B, W and X, and is C2 to C10 alkylene, in which one non-terminal carbon atom may be replaced by O; and Z is (II), (III), (IV), (V), (VI), or (VII) wherein R, Rand Rare independently H or C1 to C15 hydrocarbyl, in which up to 3 carbon atoms may be replaced by O or N, and up to 3 hydrogen atoms may be replaced by halogen, and Q is H or methyl, or Q is linked to Ror Rto form a five-membered ring or Q is linked to Rto form a six-membered ring
