Design, synthesis, and biological evaluation of indole derivatives as novel nociceptin/orphanin FQ (N/OFQ) receptor antagonists.
A novel series of 2-(1,2,4-oxadiazol-5-yl)-1H-indole derivatives as nociceptin/orphanin FQ (N/OFQ) receptor antagonists was discovered. Systematic modification of our original lead by changing the pendant functional groups, linker, heterocyclic core, and basic side chain revealed the structure-activity requirements for this novel template and resulted in the identification of more potent analog with improved potency as compared to the parent compound.
Sugimoto
Yuichi
Y
Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd, Okubo-3, Tsukuba 300-2611, Ibaraki, Japan. yuichi_sugimoto@merck.com
Shimizu
Atsushi
A
Kato
Tetsuya
T
Satoh
Atsushi
A
Ozaki
Satoshi
S
Ohta
Hisashi
H
Okamoto
Osamu
O
D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects; D006224:Cricetinae; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
D007211:Indoles; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor