The design and synthesis of a novel quinolizidine template for potent opioid and opioid receptor-like (ORL1, NOP) receptor ligands.
A new class of high affinity opioid and opioid receptor-like receptor (ORL1 receptor, NOP receptor) ligands has been designed by conformational restriction of piperidine-based NOP receptor ligands, resulting in a novel quinolizidine scaffold. Different modifications of the pendant functional groups on the scaffold provide differential activities at the opioid and NOP receptors. While the conformational rigidity will provide an improved understanding of the NOP and opioid receptor binding pockets, these compounds also provide a new template for the design of novel opiate and NOP ligands.
Jong
Ling
L
Biosciences Division, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA.
Zaveri
Nurulain
N
Toll
Lawrence
L
D000701:Analgesics, Opioid / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D008024:Ligands; D009292:Narcotic Antagonists / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011807:Quinolizines / Q000138:chemical synthesis* / Q000378:metabolism*; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism*; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
D000701:Analgesics, Opioid; D008024:Ligands; D009292:Narcotic Antagonists; D011807:Quinolizines; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor