Synthesis and pharmacological evaluation of 6,7-indolo/thiazolo-morphinans--further SAR of levorphanol.
To further extend the structure-activity relationships of levorphanol, two series of novel morphinans were prepared by incorporation of an indole or aminothiazole fragment to the hexyl ring (ring C) in levorphanol. Such morphinans differed from previously reported ligands in that such indole- or aminothiazole-containing morphinans displayed enhanced binding affinity to the delta opioid receptor, while the affinity to kappa and micro receptors was slightly reduced.
Zhang
Ao
A
Bioorganic and Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. aozhang@mail.shcnc.ac.cn
Li
Fuying
F
Ding
Chunyong
C
Yao
Qizhen
Q
Knapp
Brian I
BI
Bidlack
Jean M
JM
Neumeyer
John L
JL
D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D007981:Levorphanol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D011869:Radioligand Assay; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000701:Analgesics, Opioid; D007211:Indoles; D013844:Thiazoles; D007981:Levorphanol