Fluorinated non-imidazole histamine H3 receptor antagonists.
Fluorine substituents have become a widespread and important component in drug design and development. Here, the synthesis of fluorine containing compounds and some corresponding precursor molecules are presented for potential isotope labelling as well as their data obtained with in vitro and in vivo screenings. The compounds vary in the basic centres (piperidine or pyrrolidine) and are fluoro substituted in different positions of the basic alicyclic moiety. Pharmacological evaluation resulted in ligands with high affinities at hH(3) receptor in the nanomolar and subnanomolar concentration range and some with high antagonist in vivo potencies.
Isensee
K
K
Johann Wolfgang Goethe-Universität, Institut für Pharmazeutische Chemie, Biozentrum, ZAFES/LiFF/CMP, Frankfurt, Germany.
Amon
M
M
Garlapati
A
A
Galaparti
A
A
Ligneau
X
X
Camelin
J-C
JC
Capet
M
M
Schwartz
J-C
JC
Stark
H
H
D000818:Animals; D005461:Fluorine / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D054828:Histamine H3 Antagonists / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D018100:Receptors, Histamine H3 / Q000737:chemistry / Q000378:metabolism*
D054828:Histamine H3 Antagonists; D007093:Imidazoles; D018100:Receptors, Histamine H3; D005461:Fluorine