2298-29-5

Upstream product

• 123-30-8 4-amino-phenol 
• 103-71-9 phenyl isocyanate 
• 201230-82-2 carbon monoxide 
• 62-53-3 aniline 
• 1566-41-2 1-(4-hydroxyphenyl)urea 
• 5416-93-3 4-Methoxyphenyl isocyanate 
• 3746-53-0 N-(4-metoxyphenyl)-N'-phenylurea 
• 71-43-2 benzene 
• 27574-53-4 4-hydroxybenzoyl azide 

Downstream Products

• 94042-53-2 N-(3',5'-bis(1-pyrrolidinylmethyl)-4'-hydroxyphenyl)-N'-phenylurea 
• 1343498-49-6 ethyl 5-{4-[(anilinocarbonyl)amino]phenoxy}pentanoate 
• 38924-11-7 1-[4-(1-Amino-4-hydroxy-9,10-dioxo-9,10-dihydro-anthracen-2-yloxy)-phenyl]-3-phenyl-urea 
• 1256394-33-8 1-(4-((6,7-dimethoxyquinazolin-4-yl)oxy)phenyl)-3-phenylurea 

Relevant academic research and scientific papers

Synthesis, biological evaluation, and molecular docking of new series of antitumor and apoptosis inducers designed as VEGFR-2 inhibitors

Based on quinazoline, quinoxaline, and nitrobenzene scaffolds and on pharmacophoric features of VEGFR-2 inhibitors, 17 novel compounds were designed and synthesised. VEGFR-2 IC50 values ranged from 60.00 to 123.85 nM for the new derivatives compared to 54.00 nM for sorafenib. Compounds 15a, 15b, and 15d showed IC50 from 17.39 to 47.10 μM against human cancer cell lines; hepatocellular carcinoma (HepG2), prostate cancer (PC3), and breast cancer (MCF-7). Meanwhile, the first in terms of VEGFR-2 inhibition was compound 15d which came second with regard to antitumor assay with IC50 = 24.10, 40.90, and 33.40 μM against aforementioned cell lines, respectively. Furthermore, Compound 15d increased apoptosis rate of HepG2 from 1.20 to 12.46% as it significantly increased levels of Caspase-3, BAX, and P53 from 49.6274, 40.62, and 42.84 to 561.427, 395.04, and 415.027 pg/mL, respectively. Moreover, 15d showed IC50 of 253 and 381 nM against HER2 and FGFR, respectively.

Palladium-Catalyzed Aerobic Oxidative Carbonylation of Amines Enables the Synthesis of Unsymmetrical N,N′-Disubstituted Ureas

A ligand-free palladium-catalyzed aerobic oxidative carbonylation of amines for the synthesis of ureas, particular unsymmetrically N,N′-disubstituted ureas, which cannot be accessed by any other palladium-catalyzed oxidative carbonylation of amines to date, is presented. An array of symmetrical and unsymmetrical ureas were straightforwardly synthesized by using inexpensive, readily available, stable, and safe amines with good to excellent yields under a pressure of 1 atm. This novel method employs oxygen as the sole oxidant and offers an attractive alternative to transition-metal-based oxidant systems.

Discovery of BPR1R024, an Orally Active and Selective CSF1R Inhibitor that Exhibits Antitumor and Immunomodulatory Activity in a Murine Colon Tumor Model

Colony-stimulating factor-1 receptor (CSF1R) is implicated in tumor-associated macrophage (TAM) repolarization and has emerged as a promising target for cancer immunotherapy. Herein, we describe the discovery of orally active and selective CSF1R inhibitors by property-driven optimization of BPR1K871 (9), our clinical multitargeting kinase inhibitor. Molecular docking revealed an additional nonclassical hydrogen-bonding (NCHB) interaction between the unique 7-aminoquinazoline scaffold and the CSF1R hinge region, contributing to CSF1R potency enhancement. Structural studies of CSF1R and Aurora kinase B (AURB) demonstrated the differences in their back pockets, which inspired the use of a chain extension strategy to diminish the AURA/B activities. A lead compound BPR1R024 (12) exhibited potent CSF1R activity (IC50 = 0.53 nM) and specifically inhibited protumor M2-like macrophage survival with a minimal effect on antitumor M1-like macrophage growth. In vivo, oral administration of 12 mesylate delayed the MC38 murine colon tumor growth and reversed the immunosuppressive tumor microenvironment with the increased M1/M2 ratio.

Design, synthesis, and biological evaluation of novel benzo[b]thiophene-diaryl urea derivatives as potential anticancer agents

A hybrid pharmacophore approach was applied to design and synthesize a series of benzo[b]thiophene-diaryl urea derivatives 17a–g with potential anticancer effect. In vitro antiproliferative activities of all target compounds were evaluated against HT-29 a

Synthesis and biological evaluation of diaryl urea derivatives designed as potential anticarcinoma agents using de novo structure-based lead optimization approach

To develop inhibitors blocking VEGFR2 and the Raf/MEK/ERK mitogen-activated protein kinase signaling pathway new compounds based on sorafenib were designed, synthesized and biologically evaluated. Using de novo design method, a library of new ligands was

Sulfonimide and amide derivatives as novel PPARα antagonists: Synthesis, antiproliferative activity, and docking studies

An agonist?antagonist switching strategy was performed to discover novel PPARα antagonists. Phenyldiazenyl derivatives of fibrates were developed, bearing sulfonimide or amide functional groups. A second series of compounds was synthesized, replacing the

Direct conversion of carboxylic acids to various nitrogen-containing compounds in the one-pot exploiting curtius rearrangement

Herein we report, a single-pot multistep conversion of inactivated carboxylic acids to various N-containing compounds using a common synthetic methodology. The developed methodology rendered the use of carboxylic acids as a direct surrogate of primary amines, for the synthesis of primary ureas, secondary/tertiary ureas, O/S-carbamates, benzoyl ureas, amides, and N-formyls, exploiting the Curtius reaction. This approach has a potential to provide a diversified library of N-containing compounds, starting from a single carboxylic acid, based on the selection of the nucleophile.

Design and synthesis of phthalazine-based compounds as potent anticancer agents with potential antiangiogenic activity via VEGFR-2 inhibition

In the designed compounds, either a biarylamide or biarylurea moiety or an N-substituted piperazine motif was linked to position 1 of the phthalazine core. The anti-proliferative activity of the synthesised compounds revealed that eight compounds (6b, 6e, 7b, 13a, 13c, 16a, 16d and 17a) exhibited excellent broad spectrum cytotoxic activity in NCI 5-log dose assays against the full 60 cell panel with GI50 values ranging from 0.15 to 8.41 μM. Moreover, the enzymatic assessment of the synthesised compounds against VEGFR-2 tyrosine kinase showed the significant inhibitory activities of the biarylureas (12b, 12c and 13c) with IC50s of 4.4, 2.7 and 2.5 μM, respectively, and with 79.83, 72.58 and 71.6% inhibition of HUVEC at 10 μM, respectively. Additionally, compounds (7b, 13c and 16a) were found to induce cell cycle arrest at S phase boundary. Compound 7b triggered a concurrent increase in cleaved caspase-3 expression level, indicating the apoptotic-induced cell death.

Attenuation of Mycobacterium species through direct and macrophage mediated pathway by unsymmetrical diaryl urea

Tuberculosis is a major threat for mankind and the emergence of resistance strain of Mycobacterium tuberculosis (Mtb) against first line antibiotics makes it lethal for human civilization. In this study, we have synthesized different diaryl urea derivativ

Synthesis and SAR studies of potent H+/K+-ATPase and anti-inflammatory activities of symmetrical and unsymmetrical urea analogues

A sequence of symmetrical and unsymmetrical urea derivatives 1–24 were synthesized and characterized by standard spectroscopic techniques. The synthesized analogues were tested for their in vitro H+/K+-ATPase and anti-inflammatory activities. The majority of the compounds showed outstanding activity, compared to that of omeprazole and indomethacin, usual standard drugs of antiulcer and anti-inflammatory, respectively. In particular, hydroxy, methyl, and methoxy derivatives 13–24 were the most active compounds possessing a significant amplify for diverse substituents on the benzene ring thus, contributing positively to gastric ulcer inhibition. Compounds 1–3 and 22–24 showed excellent anti-inflammatory activity due to the presence of electron-withdrawing groups (Cl and F) on the molecule.