Design, synthesis and evaluation of a novel cyclohexanamine class of neuropeptide Y Y1 receptor antagonists.
A novel series of cyclohexanamine derivatives was designed and synthesized as potent and selective human neuropeptide Y Y1 receptor antagonists. Modification of high-throughput screening hit compound 1 resulted in the identification of compound 3i, which displays potent Y1 activity and good selectivity towards hERG K(+) channel and serotonin transporter.
Cho
Kaimei
K
Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Company, Ltd, 3 Okubo, Tsukuba 300-2611, Japan. kaimei_cho@yahoo.co.jp
Ando
Makoto
M
Kobayashi
Kensuke
K
Miyazoe
Hiroshi
H
Tsujino
Toshiaki
T
Ito
Sayaka
S
Suzuki
Tomoki
T
Tanaka
Takeshi
T
Tokita
Shigeru
S
Sato
Nagaaki
N
D002460:Cell Line; D003514:Cyclohexylamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D006801:Humans; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013329:Structure-Activity Relationship
D003514:Cyclohexylamines; D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D012701:Serotonin