Analogues and derivatives of ciproxifan, a novel prototype for generating potent histamine H3-receptor antagonists

H Stark; X Ligneau; B Sadek; C R Ganellin; J M Arrang; J C Schwartz; W Schunack

doi:10.1016/s0960-894x(00)00473-x

Analogues and derivatives of ciproxifan, a novel prototype for generating potent histamine H3-receptor antagonists

Bioorg Med Chem Lett. 2000 Oct 16;10(20):2379-82. doi: 10.1016/s0960-894x(00)00473-x.

Authors

H Stark¹, X Ligneau, B Sadek, C R Ganellin, J M Arrang, J C Schwartz, W Schunack

Affiliation

¹ Institut für Pharmazie, Freie Universität Berlin, Germany. stark@schunet.pharmazie.fu-berlin.de

PMID: 11055360
DOI: 10.1016/s0960-894x(00)00473-x

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cerebral Cortex / physiology
Drug Design
Histamine Antagonists / chemical synthesis*
Histamine Antagonists / chemistry
Histamine Antagonists / pharmacology
Histamine Release / drug effects*
Imidazoles / chemical synthesis*
Imidazoles / chemistry*
Imidazoles / pharmacology
Molecular Structure
Rats
Receptors, Histamine H3 / drug effects*
Receptors, Histamine H3 / physiology
Structure-Activity Relationship
Synaptosomes / drug effects
Synaptosomes / physiology

Substances

Histamine Antagonists
Imidazoles
Receptors, Histamine H3
ciproxifan