《4-Aryl-1-oxa-4,9-diazaspiro[5.5]undecane derivatives as dual μ-opioid receptor agonists and σ1 receptor antagonists for the treatment of pain》 was published in Journal of Medicinal Chemistry in 2020. These research results belong to Garcia, Monica; Virgili, Marina; Alonso, Monica; Alegret, Carles; Fernandez, Begona; Port, Adriana; Pascual, Rosalia; Monroy, Xavier; Vidal-Torres, Alba; Serafini, Maria-Teresa; Vela, Jose Miguel; Almansa, Carmen. Category: iodides-buliding-blocks The article mentions the following:
The synthesis and pharmacol. activity of a new series of 1-oxa-4,9-diazaspiro[5.5]undecane derivatives as potent dual ligands for the sigma-1 receptor (σ1R) and the μ-opioid receptor (MOR) are reported. The different positions of the central scaffold, designed using a merging strategy of both targets pharmacophores, were explored using a versatile synthetic approach. Phenethyl derivatives in position 9, substituted pyridyl moieties in position 4 and small alkyl groups in position 2 provided the best profiles. One of the best compounds, I, showed a balanced dual profile (i.e. MOR agonism and sigma antagonism) and potent analgesic activity, comparable to the MOR agonist oxycodone in the paw pressure test in mice. Contrary to oxycodone, as expected from the addition of σ1R antagonism, I showed local, peripheral activity in this test, which was reversed by the σ1R agonist PRE-084. At equianalgesic doses, I showed less constipation than oxycodone, providing evidence that dual MOR agonism and σ1R antagonism may be a useful strategy for obtaining potent and safer analgesics. The experimental part of the paper was very detailed, including the reaction process of Trimethylsulfoxonium iodide(cas: 1774-47-6Category: iodides-buliding-blocks)
Trimethylsulfoxonium iodide(cas: 1774-47-6) reacts with sodium hydride to prepare dimethyloxosulfonium methylide, which is used as a methylene-transfer reagent in synthetic chemistry. It is used to prepare ylide, which reacts with carbonyl compounds to get epoxides.Category: iodides-buliding-blocks
Referemce:
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com