203448-32-2

Upstream product

• 874812-62-1 2-methoxy-5-(3,4,5-trimethoxybenzoyl)phenyl 2-chloroacetate 
• 154083-41-7 3-((tert-butyldimethylsilyl)oxy)-4-methoxybenzoic acid 
• 203448-31-1 N-[(3-tertbutyldimethylsilyl)oxy-4-methoxybenzoyl]morpholine 
• 2675-79-8 1-bromo-3,4,5-trimethoxybenzene 
• 185698-55-9 2-(3-hydroxy-4-methoxyphenyl)-1-(3',4',5'-trimethoxyphenyl)ethyne 
• 53560-33-1 3,4,5-trimethoxyphenylacetylene 
• 1415342-82-3 (3-((tert-butyldimethylsilyl)oxy)-4-methoxyphenyl)(3,4,5-trimethoxyphenyl)methanol 
• 621-59-0 isovanillin 
• 30287-15-1 2-methoxyphenyl 2-chloroacetate 
• 118-41-2 Eudesmic acid 
• 90-05-1 2-methoxy-phenol 
• 177329-71-4 5-Bromo-1-(tert-butyldimethylsilyloxy)-2-methoxybenzene 
• 118779-14-9 N-methoxy-N-methyl-3,4,5-trimethoxybenzamide 
• 121042-95-3 (Z)-5-(3-tert-butyldimethylsilyloxy-4-methoxystyryl)-1,2,3-trimethoxybenzene 

Downstream Products

• 203448-33-3 3-O-dibenzylphosphoryl-phenstatin 
• 229027-06-9 Phosphoric acid mono-[2-methoxy-5-(3,4,5-trimethoxy-benzoyl)-phenyl] ester 
• 22699-97-4 (3,4-dimethoxyphenyl)(3,4,5-trimethoxyphenyl)methanone 
• 944645-51-6 (3,4-dimethoxyphenyl)(3,4,5-trimethoxyphenyl)methanol 
• 138958-69-7 5-[hydroxy(3,4,5-trimethoxyphenyl)methyl]-2-methoxyphenol 
• 1452531-55-3 C₃₅H₅₂O₇ 
• 1452531-58-6 C₃₅H₅₀O₇ 
• 1452531-61-1 C₃₅H₄₈O₇ 

Relevant academic research and scientific papers

Synthesis and biological evaluation of novel hybrids of phenylsulfonyl furoxan and phenstatin derivatives as potent anti-tumor agents

Hybridization of nitric oxide (NO) donors with known anti-cancer agents have been emerged as a strategy to achieve improved therapeutic effect and to overcome chemo-resistance in cancer therapy. In this study, furoxan moiety as an efficient NO donor was i

Synthesis and biological evaluation of 1‐(Diarylmethyl)‐1h‐1,2,4‐triazoles and 1‐(diarylmethyl)‐1h‐imidazoles as a novel class of anti‐mitotic agent for activity in breast cancer

We report the synthesis and biochemical evaluation of compounds that are designed as hybrids of the microtubule targeting benzophenone phenstatin and the aromatase inhibitor letrozole. A preliminary screening in estrogen receptor (ER)‐positive MCF‐7 breast cancer cells identified 5‐((2H‐1,2,3‐triazol‐1‐yl)(3,4,5‐trimethoxyphenyl)methyl)‐2‐methoxyphenol 24 as a potent antiproliferative compound with an IC50 value of 52 nM in MCF‐7 breast cancer cells (ER+/PR+) and 74 nM in triple‐negative MDA‐MB‐231 breast cancer cells. The compounds demonstrated significant G2/M phase cell cycle arrest and induction of apoptosis in the MCF‐7 cell line, inhibited tubulin polymerisation, and were selective for cancer cells when evaluated in non-tumorigenic MCF‐10A breast cells. The immunofluorescence staining of MCF‐7 cells confirmed that the compounds targeted tubulin and induced multinucleation, which is a recognised sign of mitotic catastrophe. Computational docking studies of compounds 19e, 21l, and 24 in the colchicine binding site of tubulin indicated potential binding conformations for the compounds. Compounds 19e and 21l were also shown to selectively inhibit aromatase. These compounds are promising candidates for development as antiproliferative, aromatase inhibitory, and microtubule‐disrupting agents for breast cancer.

Enhanced antitumor potential induced by chloroacetate-loaded benzophenones acting as fused tubulin-pyruvate dehydrogenase kinase 1 (PDHK1) ligands

The majority of cancers detected every year are treated with anti-cancer compounds. Unfortunately, many tumors become resistant to antineoplastic drugs. One option is to use cocktails of compounds acting on different targets to try to overcome the resista

Acid-Promoted Intramolecular Decarbonylative Coupling Reactions of Unstrained Ketones: A Modular Approach to Synthesis of Acridines and Diaryl Ketones

Herein, we reported Lewis acid-or Br?nsted acid-promoted intramolecular C(sp2)-C(sp2) bond cleavage and a novel C(sp2)-C(sp2) bond-forming cascade reaction to synthesize the acridine motif. The metal-free oxidation of the alkyne motif generated the in situ ketone group extracted via a decarbonylation reaction. The mechanistic studies revealed that the electrophilic N-iodo species triggered key decarbonylation reactions via consecutive dearomatization/aromatization reactions. In addition, we exploited this acid-promoted C-C bond activation system with internal alkynes to synthesize bis(heteroaryl) ketones.

Platinum(IV) complexes conjugated with phenstatin analogue as inhibitors of microtubule polymerization and reverser of multidrug resistance

Pt(IV) complexes comprising a phenstatin analogue, as dual-targeting Pt(IV) prodrug, were designed and synthesized. They were found not only to carry the DNA binding platinum warhead into the tumor cells, but also to have a small molecular unit to inhibit tubulin polymerization. In vitro evaluation results revealed that Pt(IV) complexes showed better and more potent activity against the test human cancer cells including cisplatin resistant cell lines than their corresponding Pt(II) counterparts. In addition, the Pt(IV) derivative of cisplatin, complex 10, exhibited highly selective inhibition in human cancer cells and displayed no obvious toxicity to two human normal cell lines, respectively. Mechanism study suggested that complex 10 induced cell-cycle arrest at the G2/M phase and caused apoptotic cell death of human lung cancer NCI-H460 cells through the mitochondrial mediated pathway. Moreover, complex 10 effectively inhibited the tumor growth in the NCI-H460 xenograft model.

Bioreductively activatable prodrug conjugates of phenstatin designed to target tumor hypoxia

A variety of solid tumor cancers contain significant regions of hypoxia, which provide unique challenges for targeting by potent anticancer agents. Bioreductively activatable prodrug conjugates (BAPCs) represent a promising strategy for therapeutic intervention. BAPCs are designed to be biologically inert until they come into contact with low oxygen tension, at which point reductase enzyme mediated cleavage releases the parent anticancer agent in a tumor-specific manner. Phenstatin is a potent inhibitor of tubulin polymerization, mimicking the chemical structure and biological activity of the natural product combretastatin A-4. Synthetic approaches have been established for nitrobenzyl, nitroimidazole, nitrofuranyl, and nitrothienyl prodrugs of phenstatin incorporating nor-methyl, mono-methyl, and gem-dimethyl variants of the attached nitro compounds. A series of BAPCs based on phenstatin have been prepared by chemical synthesis and evaluated against the tubulin-microtubule protein system. In a preliminary study using anaerobic conditions, the gem-dimethyl nitrothiophene and gem-dimethyl nitrofuran analogues were shown to undergo efficient enzymatic cleavage in the presence of NADPH cytochrome P450 oxidoreductase. Each of the eleven BAPCs evaluated in this study demonstrated significantly reduced inhibitory activity against tubulin in comparison to the parent anti-cancer agent phenstatin (IC50?=?1.0?μM). In fact, the majority of the BAPCs (seven of the eleven analogues) were not inhibitors of tubulin polymerization (IC50?>?20?μM), which represents an anticipated (and desirable) attribute for these prodrugs, since they are intended to be biologically inactive prior to enzyme-mediated cleavage to release phenstatin.

Supercritical fluid chromatography approach for a sustainable manufacture of new stereoisomeric anticancer agent

Two routes aimed at the manufacture of unprecedented stereoisomeric combretastatin A-4 analogue were described: flash chromatography vs supercritical fluid chromatography. The latter has many advantages over liquid chromatography and was therefore chosen for the small scale separation of methyl 1-[(3-hydroxy-4-methoxyphenyl) (3,4,5-trimethoxyphenyl)methyl]-5-oxo-L-prolinate 5, with potential antitumoral activity. After a screening of six different polysaccharide based chiral stationary phases and four co-solvents, the percentage of co-solvent, the flow-rate and the outlet pressure were optimized through a design of experiments (DoE). The preparation of 50 mg of each stereoisomer was achieved successfully on a Chiralpak AD-H with isopropanol as a co-solvent. Productivity (kkd), solvent usage and environmental factor (E Factor) were calculated. Flash chromatography and supercritical fluid chromatography approaches were compared in terms of yield and purity of each stereoisomer manufactured.

Eaton's reagent-mediated domino π-cationic arylations of aromatic carboxylic acids to iasi-red polymethoxylated polycyclic aromatic hydrocarbons: Products with unprecedented biological activities as tubulin polymerization inhibitors

A rapid domino π-cationic arylation of aromatic carboxylic acids, mediated by Eaton's reagent, has been developed for the synthesis of Iasi-red polymethoxylated polycyclic aromatic hydrocarbons (PAHs). This route is currently the easiest method to obtain

New phenstatin-fatty acid conjugates: Synthesis and evaluation

New phenstatin-fatty acid conjugates have been synthesized and tested against the KB-3-1, H460, MCF-7 and HEK293 cell lines, with an increase in anti-proliferative activity being observed at the micro-molar level paralleling an increase in un-saturation in the fatty acid component.

On the synthesis and biological properties of isocombretastatins: A case of ketone homologation during Wittig reaction attempts

New isocombretastatins were synthesized by reacting the corresponding phenstatin analogs with CH3PPh3Br in presence of tBuOK. These new derivatives showed significant activities against cellular proliferation and tubulin polymerization. In particular, monomethoxylated derivatives of phenstatin and isoCA-4 exhibit similar activities to those of parent phenstatin. Attempts of the Wittig reaction on 2- (or 4-) methoxy-4′-nitrobenzophenones in the same conditions do not lead to the expected isocombretastatins but to methyleneketones with the exclusion of triphenylphosphine. A mechanism for this new ketone homologation was proposed.