A novel series of piperidin-4-yl-1,3-dihydroindol-2-ones as agonist and antagonist ligands at the nociceptin receptor.
A series of N-(4-piperidinyl)-2-indolinones were discovered as a new structural class of nociceptin receptor (NOP) ligands. Unlike other previously reported classes of NOP receptor ligands, modifications of the piperidine N substituents afforded both potent agonists and antagonists, with modest selectivities over other opioid receptors. The SAR revealed in this new series will provide important insights for the development of pharmacophores for agonist and antagonist actions at the NOP receptor.
Zaveri
Nurulain T
NT
Biosciences Division, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA. nurulain.zaveri@sri.com
Jiang
Faming
F
Olsen
Cris M
CM
Deschamps
Jeffrey R
JR
Parrish
Damon
D
Polgar
Willma
W
Toll
Lawrence
L
D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D009292:Narcotic Antagonists; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000819:agonists*; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
D007211:Indoles; D008024:Ligands; D009292:Narcotic Antagonists; D010880:Piperidines; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor