77853-46-4Relevant academic research and scientific papers
Divergent Nickel-Catalysed Ring-Opening-Functionalisation of Cyclobutanone Oximes with Organozincs
Angelini, Lucrezia,Leonori, Daniele,Malet Sanz, Laia
supporting information, p. 37 - 40 (2019/12/30)
The development of a nickel-catalysed strategy for the remote alkylation, arylation, vinylation and alkynylation of nitriles is presented. The methodology uses electron-poor O-Ar cyclic oximes and organozincs as coupling partners. This redox process proceeds through the generation of an iminyl radical and its following ring-opening reaction.
Low-Valent Titanium-Mediated Radical Conjugate Addition Using Benzyl Alcohols as Benzyl Radical Sources
Suga, Takuya,Shimazu, Shoma,Ukaji, Yutaka
, p. 5389 - 5392 (2018/09/12)
A concise method to directly generate benzyl radicals from benzyl alcohol derivatives has been developed. The simple and inexpensive combination of TiCl4(collidine) (collidine = 2,4,6-collidine) and manganese powder afforded a low-valent titanium reagent, which facilitated homolytic cleavage of benzylic C-OH bonds. The application to radical conjugate addition reactions demonstrated the broad scope of this method. The reaction of various benzyl alcohol derivatives with electron-deficient alkenes furnished the corresponding radical adducts.
Nucleophilic Amination of Methoxy Arenes Promoted by a Sodium Hydride/Iodide Composite
Kaga, Atsushi,Hayashi, Hirohito,Hakamata, Hiroyuki,Oi, Miku,Uchiyama, Masanobu,Takita, Ryo,Chiba, Shunsuke
, p. 11807 - 11811 (2017/09/20)
A method for the nucleophilic amination of methoxy arenes was established by using sodium hydride (NaH) in the presence of lithium iodide (LiI). This method offers an efficient route to benzannulated nitrogen heterocycles. Mechanistic studies showed that the reaction proceeds through an unusual concerted nucleophilic aromatic substitution.
New serotonin 5-HT1A receptor agonists endowed with antinociceptive activity in vivo
Valhondo, Margarita,Marco, Isabel,Martín-Fontecha, Mar,Vázquez-Villa, Henar,Ramos, José A.,Berkels, Reinhard,Lauterbach, Thomas,Benhamú, Bellinda,López-Rodríguez, María L.
, p. 7851 - 7861 (2013/11/06)
We report the synthesis of new compounds 4-35 based on two different openings (A and B) of the chromane ring present in the previously identified 5-HT1A receptor (5-HT1AR) ligand 3. The synthesized compounds were assessed for binding affinity, selectivity, and functional activity at the 5-HT1AR. Selected candidates resulting from B opening were also evaluated for their potential antinociceptive effect in vivo and pharmacokinetic properties in vitro. Analogue 19 [2-(4-{[2-(2-ethoxyphenoxy) ethyl]amino}butyl)tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione] has been characterized as a high-affinity and potent 5-HT1AR agonist (K i = 2.3 nM; EC50 = 19 nM). Pharmacokinetic studies indicated that compound 19 displays a good metabolic stability in human liver microsomes (t1/2 ～ 3 h and CLint = 3.5 mL/min/kg, at 5 μM), and a low level of protein binding (25%, at 5 μM). Interestingly, 19 (3 mg/kg, ip, and 30 mg/kg, po) caused significant attenuation of formalin-induced behavior in early and late phases of the mouse intradermal formalin test of pain, and this in vivo effect was reversed by the selective 5-HT1AR antagonist WAY-100635. Thus, the new 5-HT1AR agonist identified in this work, 19, exhibits oral analgesic activity, and the results herein represent a step toward identifying new therapeutics for the control of pain.
