39193-07-2Relevant articles and documents
Synthesis of ring-opened derivatives of triazole-containing quinolinones and their antidepressant and anticonvulsant activities
Song, Ming-Xia,Huang, Yu-Shan,Zhou, Qiu-Gui,Deng, Xian-Qing,Yao, Xiao-Dong
, (2020/12/07)
Based on the potent antidepressant and anticonvulsant activities of the triazole-containing quinolinones reported in our previous work, a series of ring-opened derivatives of them were designed, synthesized in this work. Their antidepressant and anticonvulsant activities were screened using the forced swimming test (FST) and the maximal electroshock seizure test (MES), respectively. The results showed that compounds 4a, 5a, 6c-6e, 6g-6i, and 7 led to significant reductions in the accumulated immobility time in the FST at a dose of 50 mg/kg. Especially compound 7 exhibited higher levels of efficacy than the reference standard fluoxetine in the FST and the tail suspension test. The results of an open field test excluded the possibility of central nervous stimulation of 7, which further confirmed its antidepressant effect. Meanwhile, compounds 6a-6i and 7 showed different degrees of anticonvulsant activity in mice at the doses range from 300 to 30 mg/kg in the MES. Among them, compounds 6e and 7 displayed the ED50 of 38.5 and 32.7 mg/kg in the MES, and TD50 of 254.6 and 245.5 mg/kg, respectively. No one showed neurotoxicity at the dose of 100 mg/kg. The preliminary investigation forward to their mechanism indicated that regulation of GABAergic system might contribute to their anticonvulsive and anti-depressive action.
Synthesis of novel liquid crystalline and fire retardant molecules based on six-armed cyclotriphosphazene core containing Schiff base and amide linking units
Guan-Seng, Tay,Jamain, Zuhair,Khairuddean, Melati
, p. 28918 - 28934 (2020/08/25)
Nucleophilic substitution reaction between 4-hydroxybenzaldehyde and hexachlorocyclotriphosphazene, HCCP formed hexakis(4-formlyphenoxy)cyclotriphosphazene, 1. Intermediates 2a-e was formed from the alkylation reaction of methyl 4-hydroxybenzoate with alkyl bromide which further reduced to form benzoic acid intermediates. Further reaction of 2a-e and other substituted benzoic acid formed 3a-h, which then reduced to give subsequent amines, 4a-h. Other similar reaction was used to synthesis 4i. Condensation reaction between 1 and 4a-i yielded hexasubstituted cyclotriphosphazene compounds, 5a-i having Schiff base and amide linking units, and these compounds consist of different terminal substituents such as heptyl, nonyl, decyl, dodecyl, tetradecyl, hydroxy, carboxy, chloro, and nitro groups, respectively. Compound 5j with amino substituent at terminal end was formed from the reduction of 5i. All the intermediates and compounds were characterized using Fourier Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR) and CHN elemental analysis. Mesophase texture of these compounds were determined using Polarized Optical Microscope (POM) and their mesophase transition were further confirmed using Differential Scanning Calorimetry (DSC). Only compounds 5a-e with alkoxy chains exhibited smectic A phase while other intermediates (1, 2a-e, 3a-h, and 4a-i) and final compounds (5f-j) are found to be non-mesogenic with no liquid crystal behaviour. The confirmation of the identity of the SmA phase was determined using XRD analysis. The study on the structure-properties relationship was conducted in order to determine the effect of the terminal group, length of the chains and linking units to the mesophase behaviour of the compounds. Moreover, the fire retardant properties of these compounds were determined using Limiting Oxygen Index (LOI) testing. Polyester resin with LOI value of 22.53% was used as matrix for moulding in the study. The LOI value increased to 24.71% when this polyester resin incorporated with 1 wt% of HCCP. Generally, all the final compounds showed a positive results with LOI value above 27% and the highest LOI value was belonged to compound 5i with 28.53%. The high thermal stability of the Schiff base molecules and the electron withdrawing group of the amide bonds and nitro group enhanced the fire retardant properties of this compound.
Light-Switchable Antagonists for the Histamine H1 Receptor at the Isolated Guinea Pig Ileum
Rustler, Karin,Pockes, Steffen,K?nig, Burkhard
, p. 636 - 644 (2019/02/14)
The histamine H1 G protein-coupled receptor (GPCR) plays an important role in allergy and inflammation. Existing drugs that address the H1 receptor differ in their chemical structure, pharmacology, and side effects. Light-controllable spatial and temporal activity regulation of photochromic H1 ligands may contribute to a better mechanistic understanding and the development of improved correlations between ligand structure and pharmacologic effects. We report photochromic H1 receptor ligands, which were investigated in an organ-pharmacological assay. Initially, five photochromic azobenzene derivatives of reported dual H1–H4 receptor antagonists were designed, synthesized, photochemically characterized, and organ-pharmacologically tested on the isolated guinea pig ileum. Among them, one compound [trans-19: (Z)-1-(4-chlorophenyl)-1-(4-methylpiperazin-1-yl)-N-(4-((E)-phenyldiazenyl)phenyl)methanimine] retained the antagonistic activity of its non-photochromic lead, and trans–cis isomerization by irradiation induced a fourfold difference in the pharmacological response. Further structural optimization resulted in two bathochromically shifted derivatives of 19 [NO2-substituted 35 {(Z)-1-(4-chlorophenyl)-1-(4-methylpiperazin-1-yl)-N-(4-((E)-(4-nitrophenyl)diazenyl)phenyl)methanimine} and SO3?-substituted 41 {4-((E)-(4-(((Z)-(4-chlorophenyl)(4-methylpiperazin-1-yl)methylene)amino)phenyl)diazenyl)benzenesulfonate}], which do not require the use of UV light for photoisomerization and which also have improved solubility and show reduced tissue impairment. The trans isomers of both compounds showed a remarkable increase in antagonistic activity relative to their lead trans-19; furthermore, a 46-fold difference in activity on the isolated guinea pig ileum was observed between trans- and cis-35.
