期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 51, 期 7, 页码 2316-2320出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm701457j
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资金
- NIDA NIH HHS [DA 021049, K02 DA019634-01, K01 DA 19834, R21 DA019834, F31 DA021049, K02 DA019634] Funding Source: Medline
Continuing our studies investigating opioids with reduced P-glycoprotein (P-gp) substrate activity, a series of known 3- and 6-hydroxy, -methoxy, and -desoxymorphine analogs was synthesized and analyzed for Pgp substrate activity and opioid binding affinity. 6-Desoxymorphine (7) showed high affinity for opioid receptors and did not induce P-gp-mediated ATP hydrolysis. Additionally, 7 demonstrated morphine-like antinociceptive potency in mice, indicating this compound as an ideal lead to further evaluate the role of P-gp in opioid analgesic tolerance development.
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