A new class of diamine-based human histamine H3 receptor antagonists: 4-(aminoalkoxy)benzylamines.
4-(Aminoalkoxy)benzylamines were prepared and screened for in vitro activity at the human histamine H(3) receptor. Some members of this series exhibited subnanomolar binding affinities. Analogues in which one nitrogen atom was replaced with a methine group showed greatly reduced binding affinities. Six members of this series were found to be antagonists in a cell-based model of human histamine H(3) receptor activation. One member of this series, 1-[4-(3-piperidin-1-ylpropoxy)benzyl]piperidine (7b), was found to be a selective and potent human H(3) receptor antagonist.
Apodaca
Richard
R
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, California 92121, USA.
Dvorak
Curt A
CA
Xiao
Wei
W
Barbier
Ann J
AJ
Boggs
Jamin D
JD
Wilson
Sandy J
SJ
Lovenberg
Timothy W
TW
Carruthers
Nicholas I
NI
D000818:Animals; D001596:Benzylamines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D018938:Caco-2 Cells; D002460:Cell Line; D002540:Cerebral Cortex / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010539:Permeability; D010880:Piperidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D018100:Receptors, Histamine H3 / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
C477200:1-(4-(3-piperidin-1-ylpropoxy)benzyl)piperidine; D001596:Benzylamines; D006633:Histamine Antagonists; D010880:Piperidines; D018100:Receptors, Histamine H3; D000242:Cyclic AMP