Analogues and derivatives of ciproxifan, a novel prototype for generating potent histamine H3-receptor antagonists.
Novel derivatives of the highly potent and selective histamine H3-receptor antagonist ciproxifan (3) with different chain lengths as well as with structural variants of the cyclopropyl ketone moiety have been prepared and screened for their antagonist H3-receptor potencies in vitro and in vivo. Some derivatives (2, 6-8, 12) containing other functionalities were effective in vitro in the same (sub)nanomolar concentration range and in vivo in a remarkably low oral dose.
Stark
H
H
Institut für Pharmazie, Freie Universität Berlin, Germany. stark@schunet.pharmazie.fu-berlin.de
Ligneau
X
X
Sadek
B
B
Ganellin
C R
CR
Arrang
J M
JM
Schwartz
J C
JC
Schunack
W
W
D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology; D015195:Drug Design; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D051381:Rats; D018100:Receptors, Histamine H3 / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology
D006633:Histamine Antagonists; D007093:Imidazoles; D018100:Receptors, Histamine H3; C115705:ciproxifan