2-(4-alkylpiperazin-1-yl)quinolines as a new class of imidazole-free histamine H3 receptor antagonists.
With the aim of identifying structurally novel, centrally acting histamine H(3) antagonists, a series of 2-(4-alkylpiperazin-1-yl)quinolines was prepared. Systematic variation of the substituents led to highly potent histamine H(3) antagonists with low polar surface area and appropriate log P for blood-brain barrier penetration.
Zaragoza
Florencio
F
Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark. flo@novonordisk.com
Stephensen
Henrik
H
Peschke
Bernd
B
Rimvall
Karin
K
D000818:Animals; D001671:Biochemistry / Q000379:methods; D001812:Blood-Brain Barrier / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006633:Histamine Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D018100:Receptors, Histamine H3 / Q000187:drug effects* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D006633:Histamine Antagonists; D007093:Imidazoles; D011804:Quinolines; D018100:Receptors, Histamine H3; D011985:Receptors, Serotonin