875923-91-4

Upstream product

• 82547-19-1 N-(4'-nitrophenyl)-4-chlorobutanamide 
• 875924-09-7 N-(4'-nitrophenyl)-4-(pyrrolidin-1-yl)butanamide 
• 100-01-6 4-nitro-aniline 

Downstream Products

• 1070978-80-1 N-(4-azidophenyl)-4-(pyrrolidin-1-yl)butanamide 
• 1070977-87-5 1,3-bis(4-(4-(4-(pyrrolidin-1-yl)butanamido)phenylcarbamoyl)phenyl)urea 
• 1070978-00-5 N-(4-(4-(pyrrolidin-1-yl)butanamido)phenyl)-2-(1,2-dihydro-2,4-dioxoquinazolin-3(4H)-yl)benzamide 
• 1070977-74-0 1,3-bis(3-(4-(4-(pyrrolidin-1-yl)butanamido)phenylcarbamoyl)phenyl)urea 
• 1191091-23-2 N₄,N₅-bis(4-(4-(pyrrolidin-1-yl)butanamido)phenyl)-9,10-dihydro-9-oxoacridine-4,5-dicarboxamide 
• 1070978-48-1 1,3-bis(4-(1-(4-(4-(pyrrolidin-1-yl)butanamido)phenyl)-1H-1,2,3-triazol-4-yl)phenyl)urea 
• 1070978-38-9 1,3-bis(3-(1-(4-(4-(pyrrolidin-1-yl)butanamido)phenyl)-1H-1,2,3-triazol-4-yl)phenyl)urea 
• 1070978-51-6 1,3-bis-(2-(1-(4-(4-(pyrrolidin-1-yl)butanamido)phenyl)-1H-1,2,3-triazol-4-yl)phenyl)urea 

Relevant academic research and scientific papers

Design, synthesis and evaluation of 4,5-di-substituted acridone ligands with high G-quadruplex affinity and selectivity, together with low toxicity to normal cells

A series of 4,5-di-substituted acridones have been designed and synthesized. Several compounds show high affinity for telomeric G-quadruplex DNA in classical and competition FRET assays, together with low duplex DNA affinity, although they do not show activity in a telomerase assay or evidence of telomere shortening. They have low toxicity against a panel of cancer cell lines and a normal human fibroblast line, and produce potent senescence-based long-term growth arrest in the MCF7 and A549 cancer cell lines.

UREYLENE DERIVATIVES

The invention concerns compounds of Formula (I) or a salt, solvate or pro-drug thereof. The compounds may be used in therapy, particularly anti-cancer therapy.

Rational design of substituted diarylureas: A scaffold for binding to G-quadruplex motifs

The design and synthesis of a series of urea-based nonpolycyclic aromatic ligands with alkylaminoanilino side chains as telomeric and genomic G-quadruplex DNA interacting agents are described. Their interactions with quadruplexes have been examined by means of fluorescent resonance energy transfer melting, circular dichroism, and surface plasmon resonance-based assays. These validate the design concept for such urea-based ligands and also show that they have significant selectivity over duplex DNA, as well as for particular G-quadruplexes. The ligand-quadruplex complexes were investigated by computational molecular modeling, providing further information on structure-activity relationships. Preliminary biological studies using short-term cell growth inhibition assays show that some of the ligands have cancer cell selectivity, although they appear to have low potency for intracellular telomeric G-quadruplex structures, suggesting that their cellular targets may be other, possibly oncogene-related quadruplexes.

Click chemistry assembly of G-quadruplex ligands incorporating a diarylurea scaffold and triazole linkers

A series of diarylurea ligands were designed to interact selectively with G-quadruplexes and were synthesised using copper(I) catalysed 'click' chemistry to incorporate the 1,4-substituted 1,2,3-triazole ring into the core of the ligands; the optimal ligands demonstrate a high degree of selective telomeric G-quadruplex stabilisation and are not cytotoxic in several cancer cell lines. The Royal Society of Chemistry.

Trisubstituted acridines as G-quadruplex telomere targeting agents. Effects of extensions of the 3,6- and 9-side chains on quadruplex binding, telomerase activity, and cell proliferation

The synthesis is reported of a group of 3,6,9-trisubstituted acridine compounds as telomeric quadruplex-stabilizing ligands with systematic variations at the 3-, 6-, and 9-positions. A new microwave-assisted methodology has been developed for trisubstituted acridine synthesis. Structure-activity relationships are reported using surface plasmon resonance and a fluorescence melting assay to examine quadruplex binding, together with a telomerase inhibition assay. These reveal relationships between G-quadruplex stabilization and telomerase inhibition and optimal 3,6- and 9-substituent side-chain lengths for maximal activity. Qualitative molecular modeling using molecular dynamics simulations has been undertaken on four quadruplex-DNA complexes. Long-term exposure of MCF7 cancer cells to a subset of the most active compounds, at doses lower than the IC50 values, showed that one compound produced a marked decrease in population growth, accompanied by senescence, which is consistent with telomere targeting by this agent.