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• 39193-07-2 N-(4-nitrophenyl)-4-chlorophenyl carboxamide 
• 74-11-3 para-chlorobenzoic acid 
• 106-50-3 1,4-phenylenediamine 
• 71026-66-9 N-(tert-butoxycarbonyl)-1,4-phenylenediamine 
• 122-01-0 4-chloro-benzoyl chloride 
• 100-01-6 4-nitro-aniline 

Relevant academic research and scientific papers

Discovery of novel VEGFR-2 inhibitors embedding 6,7-dimethoxyquinazoline and diarylamide fragments

VEGF/VEGFR-2 signaling plays a critical part in tumor angiogenesis. Inhibition of this pathway has been considered as a promising approach for cancer treatment. In this work, a series of 6,7-dimethoxy-4-anilinoquinazoline derivatives bearing diarylamide moiety were designed, synthesized and evaluated as potent inhibitors of VEGFR-2 kinase. Their in vitro antiproliferation activities against two human cancer cell lines Hep-G2 and MCF-7 have also been determined. Among them, compound 14b exhibited the most potent inhibitory activity against VEGFR-2 with IC50 value of 0.016 ± 0.002 μM and it showed the most potent antiproliferative effect against Hep-G2 and MCF-7 with IC50 values at low-micromolar range. Molecular docking studies revealed that these compounds represented by the most potent compound 14b could bind well to the ATP-binding site of VEGFR-2, which suggested that compound 14b could be a potential anticancer agent targeting VEGFR-2.

Synthesis of ring-opened derivatives of triazole-containing quinolinones and their antidepressant and anticonvulsant activities

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

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.

Discovery of arylamide-5-anilinoquinazoline-8-nitro derivatives as VEGFR-2 kinase inhibitors: Synthesis, in vitro biological evaluation and molecular docking

Herein, we embarked on a structural optimization campaign aiming at the discovery of novel anticancer agents with our previously reported XL-6f as a lead compound. A library of 23 compounds has been synthesized based on the highly conserved active site of VEGFR-2. Several title compounds exhibited selective inhibitory activities against VEGFR-2, which also displayed selective anti-proliferation potency against HepG2 cell. All synthesized compounds were evaluated for anti-angiogenesis capability. Compound 7o showed the most potent anti-angiogenesis ability, the efficient cytotoxic activities (in vitro against HUVEC and HepG2 cell lines with IC50 values of 0.58 and 0.23 μM, respectively). The molecular docking analysis revealed 7o is a Type-II inhibitor of VEGFR-2 kinase. In general, these results indicated these arylamide-5-anilinoquinazoline-8-nitro derivatives are promising inhibitors of VEGFR-2 for the potential treatment of anti-angiogenesis.

Design, synthesis and molecular modeling study of certain VEGFR-2 inhibitors based on thienopyrimidne scaffold as cancer targeting agents

Different series of novel thieno [2,3-d]pyrimidine derivative (9a-d,10a-f,l,m and 15a-m) were designed, synthesized and evaluated for their ability to in vitro inhibit VEGFR-2 enzyme. Also, the cytotoxicity of the final compounds was tested against a panel of 60 different human cancer cell lines by NCI. The VEGFR-2 enzyme inhibitory results revealed that compounds 10d, 15d and 15 g are among the most active inhibitors with IC50 values of 2.5, 5.48 and 2.27 μM respectively, while compound 10a remarkably showed the highest cell growth inhibition with mean growth inhibition (GI) percent of 31.57%. It exhibited broad spectrum anti-proliferative activity against several NCI cell lines specifically on human breast cancer (T7-47D) and renal cancer (A498) cell lines of 85.5% and 77.65% inhibition respectively. To investigate the mechanistic aspects underlying the activity, further biological studies like flow cytometry cell cycle together with caspase-3 colorimetric assays were carried on compound 10a. Flow cytometric analysis on both MCV-7 and PC-3 cancer cells revealed that it induced cell-cycle arrest in the G0-G1phase and reinforced apoptosis via activation of caspase-3. Furthermore, molecular modeling studies have been carried out to gain further understanding of the binding mode in the active site of VEGFR-2 enzyme and predict pharmacokinetic properties of all the synthesized inhibitors.

Diarylurea histone deacetylation enzyme inhibitor

The invention belongs to the field of medical chemistry and particularly relates to a diarylurea histone deacetylation enzyme inhibitor, a medicine composition containing the histone deacetylation enzyme inhibitor, application of the inhibitor to preparat

Synthesis and biological evaluation of 1-(2-aminophenyl)-3-arylurea derivatives as potential EphA2 and HDAC dual inhibitors

A series of 1-(2-aminophenyl)-3-arylurea novel derivatives were synthesized and evaluated against Ephrin type-A receptor 2 (EphA2) and histone deacetylases (HDACs) kinase. Most of the compounds exhibited inhibitory activity against EphA2 and HDAC. The antiproliferative activities were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (thiazolyl blue, tetrazolium blue) against the human cancer cell lines HCT116, K562 and MCF7. Compounds 5a and b showed the most potent inhibitory activity against EphA2 and HDAC. However, compound 5b exhibited higher potency against HCT116 (IC50=5.29 μM) and MCF7 (IC50=7.42 μM). 1-(2-Aminophenyl)-3-arylurea analogues may serve as new EphA2-HDAC dual inhibitors.

Diarylureas and Diarylamides with Oxazolo[5,4-d]pyrimidine Scaffold as Angiogenesis Inhibitors

A series of oxazolopyrimidine-based ureas and amides were designed, synthesized, and biologically evaluated for their antiproliferative and antiangiogenic activities. These compounds were identified to exhibit inhibitory activities against human umbilical vein endothelial cells (HUVEC) in vitro. Among these compounds, compound 22 effectively inhibited the migration and capillary-like tube formation of human umbilical vein endothelial cells. It also exhibited a concentration-dependent inhibition on capillary sprouting from the rat aorta rings. Preliminary mechanistic studies revealed that compound 22 suppressed protein kinases activation, by decreasing PI3K and ERK 1/2 phosphorylation. These results support the further investigation of this class of compounds as potential anticancer agents.

4-substituted anilinoquinazoline derivatives, and preparation method and application thereof

The invention discloses novel 4-substituted anilinoquinazoline derivatives or pharmaceutically acceptable salts thereof, or polymorphic substances, solvates or stereomers of the 4-substituted anilinoquinazoline derivatives, and a preparation method and application thereof. The 4-substituted anilinoquinazoline compounds have favorable inhibition activities for EGFR and VEGFR-2 in a biological test and have obvious effects in an in-vitro anti-human tumor cell proliferation activity test.

NAPHTHYRIDININONES AS AURORA KINASE INHIBITORS

Naphthyridinone derivative compounds that inhibit Aurora kinase enzymes are disclosed along with pharmaceutical compositions comprising these compounds and methods for synthesizing the same. Such compounds have utility in the treatment of proliferative di