Identification of 4-(1H-imidazol-4(5)-ylmethyl)pyridine (immethridine) as a novel, potent, and highly selective histamine H(3) receptor agonist.
In this study, the piperidine ring of immepip and its analogues was replaced by a rigid heterocyclic pyridine ring. Many compounds in the series exhibit high affinity and agonist activity at the human histamine H(3) receptor. Particularly, the 4-pyridinyl analogue of immepip (1c, immethridine) is identified as a novel potent and highly selective histamine H(3) receptor agonist (pK(i) = 9.07, pEC(50) = 9.74) with a 300-fold selectivity over the closely related H(4) receptor.
Kitbunnadaj
Ruengwit
R
Leiden/Amsterdam Center of Drug Research (LACDR), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit Amsterdam, The Netherlands.
Zuiderveld
Obbe P
OP
Christophe
Bernard
B
Hulscher
Saskia
S
Menge
Wiro M P B
WM
Gelens
Edith
E
Snip
Erwin
E
Bakker
Remko A
RA
Celanire
Sylvain
S
Gillard
Michel
M
Talaga
Patrice
P
Timmerman
Henk
H
Leurs
Rob
R
D000818:Animals; D002460:Cell Line; D006168:Guinea Pigs; D017442:Histamine Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D018100:Receptors, Histamine H3 / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
D017442:Histamine Agonists; D007093:Imidazoles; D011725:Pyridines; D018100:Receptors, Histamine H3