A Short History of the Discovery and Development of Naltrexone and Other Morphine Derivatives

Au-Catalyzed Synthesis of Thiopyrano[2,3-b]indoles Featuring Tandem Rearrangement and Hydroarylation

“…The cyclic core of the newly synthesized ring systems 6 and 8 is analogous to that of biologically active indoles and natural products such as carbazoles, carbolines, salviadione, morphine, and morphine-like opioids (Figure ).…”

Strategies for DevelopingκOpioid Receptor Agonists for the Treatment of Pain with Fewer Side Effects

“…Cyclorphan has mixed weak partial MOPr agonist and antagonist activity, in combination with KOPr and DOPr agonism. Cyclorphan had antinociceptive effects in mice in the hotplate assay (Gringauz et al, 2001), with long-acting antinociceptive effects, however, adverse psychomimetic effects prevented its clinical development (Varghese and Hudlicky, 2014).…”

Asymmetric synthesis of (−)-naltrexone

“…However, despite the medical importance of naturally occurring and semi-synthetic opioid agonists, undesired side effects such as addictive properties and the potential for fatal overdoses are enormous societal problems. Therefore, semi-synthetic opioid antagonists were developed to address these growing problems 4. Naltrexone ( 6 ) was first patented in 1967 (ref.…”

“…Naltrexone ( 6 ) was first patented in 1967 (ref. 5) and is currently an important treatment option for opioid abuse and alcohol dependence 4. The C-14 hydroxyl and N -cyclopropylmethyl substituent are essential structural features that are important for (–)-naltrexone's potency and antagonistic properties 4…”