Synthesis and SAR of aminoalkoxy-biaryl-4-carboxamides: novel and selective histamine H3 receptor antagonists.
Novel 4'-[(NR1R2-1-yl)]-propoxy-biaryl-4-carboxamides were designed and synthesized. All compounds were tested for affinity at histamine H(3)receptors. Most compounds were highly potent and selective for human and rat H(3) receptors and selected examples such as A-349821 showed functional antagonism of H(3) receptors in vitro and in a mouse dipsogenia model.
Faghih
Ramin
R
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park 60064-6123, USA. ramin.fagih@abbott.com
Dwight
Wesley
W
Pan
Jia Bao
JB
Fox
Gerard B
GB
Krueger
Kathy M
KM
Esbenshade
Timothy A
TA
McVey
Jill M
JM
Marsh
Kennan
K
Bennani
Youssef L
YL
Hancock
Arthur A
AA
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000588:Amines / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D000882:Haplorhini; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D011869:Radioligand Assay; D051381:Rats; D017982:Receptors, Biogenic Amine / Q000187:drug effects / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000577:Amides; D000588:Amines; D006633:Histamine Antagonists; D017982:Receptors, Biogenic Amine; D018100:Receptors, Histamine H3