A new class of potent non-imidazole H(3) antagonists: 2-aminoethylbenzofurans.
2-aminoethylbenzofurans constitute a new class of H(3) antagonists that are more rotationally constrained than most previously reported H(3) antagonists. They retain high potency at human and rat receptors, with efficient CNS penetration observed in 35. The SAR of the basic amine moiety was compared in three different series of analogues. The greatest potency was found in analogues bearing a 2-methylpyrrolidine, a 2,5-dimethylpyrrolidine, or a 2,6-dimethylpiperidine.
Cowart
Marlon
M
Department of Neuroscience Research, Abbott Laboratories, Abbott Park, IL 60064-6123, USA. marlon.d.cowart@abbott.com
Pratt
John K
JK
Stewart
Andrew O
AO
Bennani
Youssef L
YL
Esbenshade
Timothy A
TA
Hancock
Arthur A
AA
D000588:Amines / Q000737:chemistry; D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D051381:Rats; D018100:Receptors, Histamine H3 / Q000737:chemistry / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000588:Amines; D001572:Benzofurans; D006633:Histamine Antagonists; D007093:Imidazoles; D010880:Piperidines; D011758:Pyrroles; D011759:Pyrrolidines; D018100:Receptors, Histamine H3; C054965:N-methylpyrrolidine; C029899:imidazole; C067286:2,5-dimethylpyrrole