53663-18-6

Usage

InChI:InChI=1/C16H11NO4/c18-14-12-7-3-4-8-13(12)15(19)17(14)9-10-5-1-2-6-11(10)16(20)21/h1-8H,9H2,(H,20,21)

Upstream product

• 87-41-2 2-benzofuran-1(3H)-one 
• 1074-82-4 potassium phtalimide 
• 409109-51-9 2-phthalimidomethyl-benzoic acid ethyl ester 
• 345927-99-3 α-phthalimido-o-toluoyl chloride 
• 7115-91-5 2-ethoxycarbonylbenzyl bromide 
• 136918-14-4 phthalimide 

Downstream Products

• 345927-99-3 α-phthalimido-o-toluoyl chloride 
• 10017-39-7 (2-benzylamino)carboxylic acid hydrochloride 
• 408527-91-3 2-((1,3-dioxoisoindolin-2-yl)methyl)benzaldehyde 
• 409109-51-9 2-phthalimidomethyl-benzoic acid ethyl ester 
• 408528-31-4 N-(2-diethoxymethyl-benzyl)-phthalimide 
• 25672-97-3 2-(aminomethyl)-benzoic acid 
• 119-67-5 o-carboxybenzaldehyde 

Relevant academic research and scientific papers

Design of a "two-in-One" Mutant-Selective Epidermal Growth Factor Receptor Inhibitor That Spans the Orthosteric and Allosteric Sites

Inhibitors targeting the epidermal growth factor receptor (EGFR) are an effective therapy for patients with non-small cell lung cancer harboring drug-sensitive activating mutations in the EGFR kinase domain. Drug resistance due to treatment-acquired mutations has motivated the development of successive generations of inhibitors that bind in the ATP site. The third-generation agent osimertinib is now a first-line treatment for this disease. Recently, allosteric inhibitors have been developed to overcome drug-resistant mutations that confer a resistance to osimertinib. Here, we present the structure-guided design and synthesis of a mutant-selective lead compound, which consists of a pyridinyl imidazole-fused benzylisoindolinedione scaffold that simultaneously occupies the orthosteric and allosteric sites. The compound potently inhibits enzymatic activity in L858R/T790M/C797S mutant EGFR (4.9 nM), with a significantly lower activity for wild-type EGFR (47 nM). Additionally, this compound achieves modest cetuximab-independent and mutant-selective cellular efficacies on the L858R (1.2 μM) and L858R/T790M (4.4 μM) variants.

Novel potent and selective DPP-4 inhibitors: Design, synthesis and molecular docking study of dihydropyrimidine phthalimide hybrids

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as antihyperglycemic agents that improve glycemic control in type 2 diabetic patients, either as monotherapy or in combination with other antidiabetic drugs. Methods: A novel series of dihydropyrimidine phthalimide hybrids was synthesized and evaluated for their in vitro and in vivo DPP-4 inhibition activity and selectivity using alogliptin as reference. Oral glucose tolerance test was assessed in type 2 diabetic rats after chronic treatment with the synthesized hybrids ± metformin. Cytotoxicity and antioxidant assays were performed. Additionally, molecular docking study with DPP-4 and structure activity relationship of the novel hybrids were also studied. Results: Among the synthesized hybrids, 10g, 10i, 10e, 10d and 10b had stronger in vitro DPP-4 inhibitory activity than alogliptin. Moreover, an in vivo DPP-4 inhibition assay revealed that 10g and 10i have the strongest and the most extended blood DPP-4 inhibitory activity compared to alogliptin. In type 2 diabetic rats, hybrids 10g, 10i and 10e exhibited better glycemic control than alogliptin, an effect that further supported by metformin combination. Finally, 10j, 10e, 10h and 10d had the highest radical scavenging activity in DPPH assay. Conclusions: Hybrids 10g, 10i and 10e are potent DPP-4 inhibitors which may be beneficial for T2DM treatment.

Novel HDAC/tubulin dual inhibitor: Design, synthesis and docking studies of α-phthalimidochalcone hybrids as potential anticancer agents with apoptosis-inducing activity

Introduction: In order to develop novel anticancer HDAC/tubulin dual inhibitors, a novel series of α-phthalimido-substituted chalcones-based hybrids was synthesized and characterized by IR,1H NMR,13C NMR, mass spectroscopy and X-ray analysis. Methods: All the synthesized compounds were evaluated for their in vitro anticancer activity against MCF-7 and HepG2 human cancer cell lines using MTT assay. To explore the mechanism of action of the synthesized compounds, in vitro β-tubulin polymerization and HDAC 1 and 2 inhibitory activity were measured for the most potent anticancer hybrids. Further, cell cycle analysis was also evaluated. Results: The trimethoxy derivative 7j showed the most potent anticancer activity, possessed the most potent β-tubulin polymerase and HDAC 1 and 2 inhibitory activity and efficiently induced cell cycle arrest at both G2/M and preG1phases in the MCF-7 cell line.

Structural optimization and structure–activity relationship of 4-thiazolidinone derivatives as novel inhibitors of human dihydroorotate dehydrogenase

Human dihydroorotate dehydrogenase (hDHODH), one of the attractive targets for the development of immunosuppressive drugs, is also a potential target of anticancer drugs and anti-leukemic drugs. The development of promising hDHODH inhibitors is in high demand. Based on the unique binding mode of our previous reported 4-thiazolidinone derivatives, via molecular docking method, three new series 4-thiazolidinone derivatives were designed and synthesized as hDHODH inhibitors. The preliminary structure–activity relationship was investigated. Compound 9 of biphenyl series and compound 37 of amide series displayed IC50 values of 1.32 μM and 1.45 μM, respectively. This research will provide valuable reference for the research of new structures of hDHODH inhibitors.

Traceless Directing Group Assisted Cobalt-Catalyzed C?H Carbonylation of Benzylamines

The first example of cobalt-catalyzed C(sp2)?H carbonylation of benzylamines using a traceless directing group is reported, which was successfully applied to the synthesis of N?unprotected iso-indolinones through direct C?H/N?H bonds activation. This protocol tolerates a variety of functional groups and provides a facile and efficient method for the formal synthesis of (+)-garenoxacin. (Figure presented.).

Cu/Fe Catalyzed Intermolecular Oxidative Amination of Benzylic C-H Bonds

We report a Cu/Fe co-catalyzed Ritter-type C-H activation/amination reaction that allows efficient and selective intermolecular functionalization of benzylic C-H bonds. This new reaction is featured by simple reaction conditions, readily available reagents and general substrate scope, allowing facile synthesis of biologically interesting nitrogen containing heterocycles. The Cu and Fe salts were found to play distinct roles in this cooperative catalysis. With a little help: A Ritter-type intermolecular amination of benzylic C-H bonds with acetonitrile, co-catalyzed by CuII/FeIII is reported. A wide array of biologically interesting nitrogen containing heterocycles was prepared from 2-alkyl benzoic acids and heteroaromatic carboxylic acids under operationally simple conditions. The Cu and Fe salts were found to play distinct roles in this cooperative catalysis.

Rationally designed squaryldiamides - A novel class of sugar-nucleotide mimics?

Sugar-nucleotides such as GDP-mannose, GDP-fucose and UDP-glucose are important biomolecules with a central role in carbohydrate and glycoconjugate biosynthesis, metabolism and cell signalling. Analogues and mimics of naturally occurring sugar-nucleotides are sought after as chemical tools and inhibitor candidates for sugar-nucleotide-dependent enzymes including glycosyltransferases. Many sugar-nucleotides bind to their target glycosyltransferases via coordination of the diphosphate group to a divalent metal cofactor in the active site. The identification of uncharged, chemically stable surrogates for the diphosphate group, with the ability to coordinate to a divalent metal, is therefore an important design criteria for the development of sugar-nucleotide mimics. Here, we describe the rational design and synthesis of a novel class of sugar-nucleotide mimics based on a squaryldiamide scaffold, an uncharged phosphate isostere. We demonstrate by comprehensive NMR titration experiments that the new sugar-nucleotide mimics coordinate efficiently to Mg2+, and provide results from biological studies with a therapeutically relevant mannosyltransferase from Trypanosoma brucei. Our findings suggest that squaryldiamides are a promising template for the development of sugar-nucleotide mimics, and illustrate the considerable potential of the squarylamide group as a fragment for inhibitor design. The Royal Society of Chemistry 2010.

SUBSTITUTED PYRROLO-PYRAZOLE DERIVATIVES ACTIVE AS KINASE INHIBITORS

Substituted pyrrolo-pyrazole derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and 5 pharmaceutical compositions comprising them are disclosed; the compounds of the inv

SUBSTITUTED PYRAZOLO [4,3-C] PYRIDINE DERIVATIVES ACTIVE AS KINASE INHIBITORS

Substituted pyrazolo[4,3-c]pyridine derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a dysregulated protein kinase activity, like cancer.

Substituted benzoyl ketones, methods for producing them and their use as herbicides

The invention relates to novel substituted benzoyl ketones of the formula (I) in which n represents 0, 1, 2 or 3, A represents a single bond or represents alkanediyl (alkylene), R1represents hydrogen or represents in each case optionally substituted alkyl or cycloalkyl, R2represents hydrogen, cyano, carbamoyl, halogen, or represents in each case optionally substituted alkyl, alkoxy, alkoxycarbonyl, alkylthio, alkylsulphinyl or alkylsulphonyl, R3represents hydrogen, nitro, cyano, carboxyl, carbamoyl, thiocarbamoyl, halogen, or represents in each case optionally substituted alkyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylamino, dialkylamino or dialkylaminosulphonyl, R4represents nitro, cyano, carboxyl, carbamoyl, thiocarbamoyl, halogen, or represents in each case optionally substituted alkyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylamino, dialkyiamino or dialkylaminosulphonyl, and Z represents an optionally substituted 4- to 12-membered, saturated or unsaturated, monocyclic or bicyclic, heterocyclic grouping which, contains 1 to 4 hetero atoms (up to 4 nitrogen atoms and optionally—alternatively or additionally—one oxygen atom or one sulphur atom, or one SO grouping or one SO2grouping) and which additionally contains one to three oxo g of the heterocycle roups (C═O) and/or thioxo groups (C═S) as components, of the heterocycle, and to processes for their preparation and to their use as herbicides.