Design, synthesis and in vivo evaluation of sodium 2-benzyl-chloromalonates as new central nervous system depressants

Abstract

This work describes the design, synthesis and in vivo evaluation of new central nervous system depressing agents that show low levels of acute toxicity, high solubility in water, and exhibit anxiolytic and hypnotic effects. These new compounds are sodium 2-benzyl-2-chloromalonates, which were designed using molecular modelling techniques and synthesized in four steps, with an overall yield between 41% and 65%. In vivo tests with mice, including pentobarbitalinduced sleep, rotarod, open field and elevated plus maze tests, were executed, and the results indicated that some of these agents induce activities similar to those induced by diazepam but with lower hypnotic potency and with greater anxiolytic potency. These compounds were also orally administered to mice in doses of 2 g/kg, and their effects were evaluated for 14 days. The mice did not show signs of intoxication, confirming that sodium 2-benzyl-2-chloromalonates exhibit low levels of acute toxicity. These observations indicate that sodium 2benzyl-2-chloromalonates and their analogues are efficient and safer central nervous system depressing drugs relative to the existing standard of care.

A Concise Sar-Analysis of Antimicrobial Cationic Amphipathic Barbiturates for an Improved Activity-Toxicity Profile

“…We therefore decided to use a stepwise approach as shown in Scheme 1-II. Barbituric acid 2 and 3,5-dibromobenzaldehyde were condensed [40] to give compound 4 and subsequent reduction with NaBH 4 in EtOH [41] gave the C-5 mono-substituted derivative 5 in 80% yield. We found 5 being an approximate 2:1 mixture of the keto and enol form.…”

Microwave-assisted synthetic method of novel Bi2O3 nanostructure and its application as a high-performance nano-catalyst in preparing benzylidene barbituric acid derivatives

“…Although some researchers have reported this reaction with the use of no catalyst (Vieira et al, 2011;Figueroa-Villar and Vieira. 2013;Vieira et al, 2015), irradiation of visible light (Kumari et al, 2021), the following catalysts are used and introduced in this regard: [DABCO](SO 3 H) 2 Cl 2 (Shirini et al, 2015), [DABCO] (SO 3 H) 2 (HSO 4 ) 2 (Seyyedi et al, 2016), p-nanoporous MMT-HClO 4 (Mashhadinezhad et al, 2018), dodecylbenzenesulfonic acid (DBSA) (Hosseini et al, 2016), FeCl 3 .6H 2 O (Kefayati et al, 2014), ethylammonium nitrate (Hu et al, 2004), silico-tungstic acid (Li and Sun, 2009), amino-sulfonic acid (Li et al, 2006), NaOH/fly ash (Gadekar and Lande, 2012), sodium p-toluene sulfonate (NaPTSA) (Kamble et al, 2010), CoFe 2 O 4 -NPs (Rajput and Karur, 2013), non-catalyst/infrared irradiation (Alarreca et al, 2000), BF 3 / nano γ-Al 2 O 3 (Mirjalili et al, 2015), succinimidinium N-sulfonic acid hydrogen sulfate ([SuSA-H]HSO 4 ) (Abedini et al, 2016), basic alumina (KhalafInezhad and Hashemi, 2001), Verjuice (Safari et al, 2019), sulfonic acid functionalized nanoporous silica (SBA-Pr-SO 3 H) (Shirini et al, 2015), copper oxide nanoparticles (CuO-NPs) (Dighore et al, 2014), aminosulfonic acid (NH 2 SO 3 H) (Li et al, 2006), 2amino-3-(4-hydroxyphenyl) propanoic acid (L-tyrosine) (Thirupathi et al, 2013), CoFe 2 O 4 nanoparticles (Rajput and Kaur, 2013), sodium acetate (CH 3 COONa) (Uttam, 2016), 1-nbutyl-3-methylimmidazolium tetrafluoroborate ([bmim]BF 4 ) (Wang et al, 2005), polyvinyl pyrrolidone stabilized nickel nanoparticles (PVP-Ni-NPs) (Khurana and Vij, 2010), cetyltrimethyl ammonium bromide (CTMAB) (Ren et al, 2002), ethyl ammonium nitrate (EAN)…”

An Efficient Microwave-Assisted Synthesis Method of Novel Bi2O3 Nanostructure and Its Application As a High-Performance Nanocatalyst in Preparing Benzylidene Barbituric Acid Derivatives

“…Although some researchers have reported this reaction with the use of no catalyst [35,36], the following catalysts are used and introduced in this regard:…”