19867-34-6Relevant articles and documents
Novel and efficient method to synthesize N-benzyl-4-formyl-piperidine
Sheng, Rong,Hu, Yongzhou
, p. 3529 - 3533 (2004)
A novel and efficient method was developed to synthesize N-benzyl-4-formyl-piperidine, a key intermediate of Donepezil (Aricept). N-Benzyl-4-piperidone was reacted with dimethyloxosulfonium methylide to get epoxide, followed by rearrangement in the presence of magnesium bromide etherate to give target compound in high yield.
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
García, Mónica,Virgili, Marina,Alonso, Mònica,Alegret, Carles,Fernández, Bego?a,Port, Adriana,Pascual, Rosalía,Monroy, Xavier,Vidal-Torres, Alba,Serafini, María-Teresa,Vela, José Miguel,Almansa, Carmen
, p. 2434 - 2454 (2019/12/25)
The synthesis and pharmacological 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 target 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, 15au, showed a balanced dual profile (i.e., MOR agonism and sigma antagonism) and a 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, 15au showed local, peripheral activity in this test, which was reversed by the σ1R agonist PRE-084. At equianalgesic doses, 15au 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.
Continuous Flow Synthesis of Terminal Epoxides from Ketones Using in Situ Generated Bromomethyl Lithium
Von Keutz, Timo,Cantillo, David,Kappe, C. Oliver
supporting information, p. 10094 - 10098 (2019/12/24)
A scalable procedure for the direct preparation of epoxides from ketones has been developed. The method is based on the carefully controlled generation of (bromomethyl)lithium (LiCH2Br) from inexpensive CH2Br2 and MeLi in a continuous flow reactor. The reaction has shown excellent selectivity for a variety of substrates, including α-chloroketones, which typically fail under classic Corey-Chaykovsky conditions. This advantage has been used to develop a novel route toward the drug fluconazole.