134697-10-2

Upstream product

• 100-02-7 4-nitro-phenol 
• 17564-64-6 N-(chloromethyl)phthalimide 
• 118-29-6 2-(hydroxymethyl)-1H-isoindole-1,3(2H)-dione 
• 5332-26-3 N-(bromomethyl)phtalimide 
• 136918-14-4 phthalimide 

Downstream Products

• 136918-14-4 phthalimide 
• 50-00-0 formaldehyd 
• 100-02-7 4-nitro-phenol 

Relevant academic research and scientific papers

Targeting Her2-insYVMA with Covalent Inhibitors - A Focused Compound Screening and Structure-Based Design Approach

Mutated or amplified Her2 serves as a driver of non-small cell lung cancer or mediates resistance toward the inhibition of its family member epidermal growth factor receptor with small-molecule inhibitors. To date, small-molecule inhibitors targeting Her2 which can be used in clinical routine are lacking, and therefore, the development of novel inhibitors was undertaken. In this study, the well-established pyrrolopyrimidine scaffold was modified with structural motifs identified from a screening campaign with more than 1600 compounds, which were applied against wild-type Her2 and its mutant variant Her2-A775_G776insYVMA. The resulting inhibitors were designed to covalently target a reactive cysteine in the binding site of Her2 and were further optimized by means of structure-based drug design utilizing a set of obtained complex crystal structures. In addition, the analysis of binding kinetics and absorption, distribution, metabolism, and excretion parameters as well as mass spectrometry experiments and western blot analysis substantiated our approach.

Synthesis and evaluation of a large library of nitroxoline derivatives as pancreatic cancer antiproliferative agents

Pancreatic cancer (PC) is one of the deadliest carcinomas and in most cases, which are diagnosed with locally advanced or metastatic disease, current therapeutic options are highly unsatisfactory. Based on the anti-proliferative effects shown by nitroxoline, an old urinary antibacterial agent, we explored a large library of newly synthesised derivatives to unravel the importance of the OH moiety and pyridine ring of the parent compound. The new derivatives showed a valuable anti-proliferative effect and some displayed a greater effect as compared to nitroxoline against three pancreatic cancer cell lines with different genetic profiles. In particular, in silico pharmacokinetic data, clonogenicity assays and selectivity indexes of the most promising compounds showed several advantages for such derivatives, as compared to nitroxoline. Moreover, some of these novel compounds had stronger effects on cell viability and/or clonogenic capacity in PC cells as compared to erlotinib, a targeted agent approved for PC treatment.

Synthesis of soft alkyl phenolic ether prodrugs using Mitsunobu chemistry

The synthesis of soft alkyl phenolic ether prodrugs in excellent yields has been reported by coupling a phenol with a hydroxymethylimide using Mitsunobu chemistry. The imides used in this study include saccharin, phthalimide, succinimide and two other compounds containing acidic imide-like N-H groups, benzotriazole, and imidazole.

Syntheses of the substituted derivatives of 2-phenoxymethyl-1H-isoindol-1,3(2H)-dione in homogeneous and heterogeneous media, under the action of electromagnetic microwaves

Some ethers derived from the 2-(phenoxymethyl)-1H-isoindol-1,3(2H)-dione were synthetized in isopropanol medium. The same compounds were also prepared in a dry medium, without solvent and absorbent inorganic support by using electromagnetic microwaves.

Mechanism of Hydrolysis of O-Imidomethyl Derivatives of Phenols

Three series of O-imidomethyl derivatives of para-substituted phenolic compounds were synthesized and their rates of hydrolysis were studied.Saccharin, phthalimide, and succinimide served as the imide portions of the derivatives.Their rates of hydrolysis were found to be first order with respect to hydroxide from pH 7.0 to 10 or 11 and dependent on the acidity (leaving group potential) of both the imide and the phenol portions.The more acidic the imide or the phenol, the faster the rate of hydrolysis.However, the rates of hydrolysis were more sensitive to the acidity of the phenol.Trapping experiments with cyanide also suggested that the phenol anion was functioning as the leaving group in what is apparently an SN2 reaction.An amide derivative was found to hydrolyze more slowly than predicted from the analogous series and the pKa of the amide.This result is apparently due partially stereoelectronic constraints in the imide series that cause the CH2-O bond to be oriented more nearly perpendicular to the plane of the C(=O)N group and hence more accessible to nucleophilic attack.

Prodrugs of biologically active hydroxyaromatic compounds

Prodrugs of bio-active hydroxyaromatic drugs having the structural formula: A pharmaceutically acceptable prodrug of a biologically active, therapeutically effective hydroxyaromatic drug, said prodrug being selected from the group consisting of, (A) compounds having the structural formula: wherein: DRUG --O-- is the hydroxyaromatic O-dehydro residue of said drug; R' and R' may be the same or different and may be H, alkyl, aryl or electron withdrawing groups; Z is a displaceable leaving group; and n is an integer in the range of from 1 to 3, and (B) pharmaceutically acceptable salts thereof.