کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1376204 | 981952 | 2008 | 4 صفحه PDF | دانلود رایگان |

Selective ring opening reaction of the N-cyclopropylmethyl group in naltrexone (1d) was effected in the presence of platinum (IV) oxide and hydrobromic acid under a hydrogen atmosphere at rt to selectively afford N-isobutyl derivative 10. The binding affinity of N-i-Bu derivative 10 for opioid receptors was 11–17 times less than that of the corresponding N-CPM compound, naltrexone (1d). However, compound 10 showed dose-dependent analgesic effects. Contrary to expectations based on previous structure–activity relationship studies for a series of N-substituted naltrexone derivatives that compound 10 would be an opioid antagonist, 10 showed dose-dependent analgesia in the mouse acetic acid writhing test (ED50: 5.05 mg/kg, sc), indicating it was an opioid agonist. This finding may have a great influence on the drug design of opioid agonists.
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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 18, 15 September 2008, Pages 4978–4981