Design and synthesis of 4-arylpiperidinyl amide and N-arylpiperdin-3-yl-cyclopropane carboxamide derivatives as novel melatonin receptor ligands.
Two series of 4-arylpiperidinyl amide and N-arylpiperdin-3-yl-cyclopropane carboxamide derivatives exhibiting diverse functionality at rat MT(1) and MT(2) receptors are reported. Compounds 11f and 18b (MT(1)/MT(2) agonist) have human microsomal intrinsic clearance comparable to ramelteon.
Department of Chemical & Pharmacokinetic Sciences, Lundbeck Research USA, 215 College Rd., Paramus, NJ 07652, USA. guli@lundbeck.com
Guiying
G
Li
Hao
H
Zhou
Yu
Y
Jiang
Holger
H
Keim
Sidney W
SW
Topiol
Suresh B
SB
Poda
Yong
Y
Ren
Gamini
G
Chandrasena
Darío
D
Doller
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008861:Microsomes / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D044122:Receptor, Melatonin, MT1 / Q000819:agonists* / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000577:Amides; D003521:Cyclopropanes; D008024:Ligands; D010880:Piperidines; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2