Identification of novel benzimidazole series of potent and selective ORL1 antagonists.
Structure-activity studies on benzimidazole lead 1 obtained from library screening led to the discovery of potent and selective ORL1 antagonist 28, 5-chloro-2-[(1-ethyl-1-methylpropyl)thio]-6-[4-(2-hydroxyethyl)piperazin-1-yl]-1H-benzimidazole, which is structurally distinct from conventional non-peptide antagonists known to date.
Okamoto
Osamu
O
Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Okubo-3, Tsukuba, Ibaraki 300-2611, Japan. osamu_okamoto@merck.com
Kobayashi
Kensuke
K
Kawamoto
Hiroshi
H
Ito
Satoru
S
Satoh
Atsushi
A
Kato
Tetsuya
T
Yamamoto
Izumi
I
Mizutani
Sayaka
S
Hashimoto
Masaya
M
Shimizu
Atsushi
A
Sakoh
Hiroki
H
Nagatomi
Yasushi
Y
Iwasawa
Yoshikazu
Y
Takahashi
Hiroyuki
H
Ishii
Yasuyuki
Y
Ozaki
Satoshi
S
Ohta
Hisashi
H
D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D015394:Molecular Structure; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
C529700:5-chloro-2-((1-ethyl-1-methylpropyl)thio)-6-(4-(2-hydroxyethyl)piperazin-1-yl)-1H-benzimidazole; D001562:Benzimidazoles; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human