40435-14-1Relevant articles and documents
Chiral guanidine catalyzed acylative kinetic resolution of racemic 2-bromo-1-arylethanols
Sawada, Erika,Nakata, Kenya
, p. 371 - 373 (2021/03/16)
In this study, chiral guanidine catalyzed acylative kinetic resolution of racemic 2-bromo-1-arylethanols was achieved with high selectivity. Irrespective of the electronic nature and the substitution patterns on the aromatic rings, a variety of substrates were suitable for this reaction. The branched acyl component was considered to be optimal for obtaining high s-values. The transition state of the reaction was proposed based on the absolute configuration of the obtained product.
Regioselective Sulfonylation/Acylation of Carbohydrates Catalyzed by FeCl3 Combined with Benzoyltrifluoroacetone and Its Mechanism Study
Dong, Hai,Liu, Yu,Lv, Jian,Zhu, Jia-Jia
, p. 3307 - 3319 (2020/03/25)
A catalytic amount of FeCl3 combined with benzoyl trifluoroacetone (Hbtfa) (FeCl3/Hbtfa = 1/2) was used to catalyze sulfonylation/acylation of diols and polyols using diisopropylethylamine (DIPEA) or potassium carbonate (K2CO3) as a base. The catalytic system exhibited high catalytic activity, leading to excellent isolated yields of sulfonylation/acylation products with high regioselectivities. Mechanism studies indicated that FeCl3 initially formed [Fe(btfa)3] (btfa = benzoyl trifluoroacetonate) with twice the amount of Hbtfa under basic conditions in the solvent acetonitrile at room temperature. Then, Fe(btfa)3 and two hydroxyl groups of the substrates formed a five- or six-membered ring intermediate in the presence of the base. The subsequent reaction between the cyclic intermediate and a sulfonylation reagent led to the selective sulfonylation of the substrate. All key intermediates were captured in the high-resolution mass spectrometry assay, therefore demonstrating this mechanism for the first time.
Development of novel LP1-based analogues with enhanced delta opioid receptor profile
Pasquinucci, Lorella,Turnaturi, Rita,Prezzavento, Orazio,Arena, Emanuela,Aricò, Giuseppina,Georgoussi, Zafiroula,Parenti, Rosalba,Cantarella, Giuseppina,Parenti, Carmela
, p. 4745 - 4752 (2017/10/05)
Pain relief achieved by co-administration of drugs acting at different targets is more effective than that obtained with conventional MOR selective agonists usually associated to relevant side effects. It has been demonstrated that simultaneously targeting different opioid receptors is a more effective therapeutic strategy. Giving the promising role for DOR in pain management, novel LP1-based analogues with different N-substituents were designed and synthesized with the aim to improve DOR profile. For this purpose, we maintained the phenyl ring in the N-substituent of 6,7-benzomorphan scaffold linked to an ethyl spacer bearing a hydroxyl/methyl or methoxyl group at carbon 2 or including it in a 1,4-benzodioxane ring. LP1 analogues were tested by competition binding assays. Compounds 6 (KiMOR = 2.47 nM, KiDOR = 9.6 nM), 7 (KiMOR = 0.5 nM and KiDOR = 0.8 nM) and 9 (KiMOR = 1.08 nM, KiDOR = 6.6 nM) retained MOR affinity but displayed an improved DOR binding capacity as compared to LP1 (KiMOR = 0.83 nM, KiDOR = 29.1 nM). Moreover, GPI and MVD functional assays indicated that compounds 6 (IC50 = 49.2 and IC50 = 10.8 nM), 7 (IC50 = 9.9 and IC50 = 11.8 nM) and 9 (IC50 = 21.5 and IC50 = 4.4 nM) showed a MOR/DOR agonist profile, unlike LP1 that was a MOR agonist/DOR antagonist (IC50 = 1.9 and IC50 = 1240 nM). Measurements of their antinociceptive effect was evaluated by mice radiant tail flick test displaying for compounds 6, 7 and 9 ED50 values of 1.3, 1.0 and 0.9 mg/kg, i.p., respectively. Moreover, the antinociceptive effect of compound 9 was longer lasting with respect to LP1. In conclusion the N-substituent nature of compounds 6, 7 and 9 shifts the DOR profile of LP1 from antagonism to agonism.