310451-86-6

Usage

Uses

Used in Pharmaceutical Industry:
2-(1,2,3,4-tetrahydro-isoquinolin-1-ylmethyl)-isoindole-1,3-dione is used as a potential drug candidate for its ability to modulate various biological targets, which may lead to the development of new therapeutic agents for the treatment of various diseases and conditions.
Used in Drug Discovery and Development:
2-(1,2,3,4-TETRAHYDRO-ISOQUINOLIN-1-YLMETHYL)-ISOINDOLE-1,3-DIONE serves as an interesting target for researchers in the field of drug discovery and development due to its unique chemical structure and potential pharmacological properties. Further studies on its bioactivity and mechanism of action could pave the way for the creation of innovative therapeutic agents.
Used in Target Modulation:
2-(1,2,3,4-tetrahydro-isoquinolin-1-ylmethyl)-isoindole-1,3-dione is used as a modulator of various biological targets, including receptors, enzymes, and transporters, for its potential to influence cellular processes and pathways related to disease progression and treatment.

InChI:InChI=1/C18H16N2O2/c21-17-14-7-3-4-8-15(14)18(22)20(17)11-16-13-6-2-1-5-12(13)9-10-19-16/h1-8,16,19H,9-11H2/p+1/t16-/m0/s1

Upstream product

• 6780-38-7 N-phthaloylglycine chloride 
• 64-04-0 phenethylamine 
• 27328-34-3 2-(2,2-dimethoyxethyl)-1H-isoindole-1,3(2H)-dione 
• 4702-13-0 N-phthaloylglycine 
• 88422-83-7 2-(3,4-dihydro-1-isoquinolinylmethyl)-1H-isoindole-1,3(2H)-dione 
• 13156-95-1 2-chloro-N-phenethylacetamide 
• 88422-74-6 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-(2-phenylethyl)acetamide 
• 85-44-9 phthalic anhydride 
• 151004-92-1 (S)-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid 
• 1432065-36-5 C₁₈H₁₉NO₃ 
• 1607007-21-5 (S)-1,5,6,10b-tetrahydro-3H-oxazolo[4,3-a]isoquinolin-3-one 
• 872986-64-6 (S)-(1,2,3,4-tetrahydroisoquinolin-1-yl)methanol 
• 1607007-22-6 (S)-(2-benzyl-1,2,3,4-tetrahydroisoquinolin-1-yl)methanol 
• 1607007-23-7 2-{[(1S)-2-benzyl-1,2,3,4-tetrahydroisoquinolin-1-yl]methyl}-2,3-dihydro-1H-isoindole-1,3-dione 

Downstream Products

• 1432500-66-7 (1S,2R)-2-[(1S)-1-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-2-carbonyl]cyclohexane-1-carboxylic acid 
• 1432065-33-2 C₂₆H₂₆N₂O₅ 
• 1432065-34-3 C₂₆H₂₆N₂O₅ 
• 1432065-35-4 C₂₆H₂₆N₂O₅ 
• 908249-20-7 2-[(1S)-1,2,3,4-tetrahydroisoquinolin-1-ylmethyl]-2,3-dihydro-1H-isoindole-1,3-dione 
• 1432065-37-6 benzyl-(1S,2R)-2-[(1S)-1-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)methyl]-1,2,3,4-tetrahydroisoquinoline-2-carbonyl]cyclohexane-1-carboxylate 
• 1207175-15-2 2-methyl-2-propanyl 1-(aminomethyl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate 

Relevant academic research and scientific papers

Tetrazanbigen Derivatives as Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Partial Agonists: Design, Synthesis, Structure-Activity Relationship, and Anticancer Activities

Tetrazanbigen (TNBG) is a novel sterol isoquinoline derivative with poor water solubility and moderate inhibitory effects on human cancer cell lines via lipoapoptosis induction. Herein, we developed a series of novel TNBG analogues with improved water sol

Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds

Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220-380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic optimization resulted in several novel analogues with Ki values of 0.04-0.5 μM, binding modes determined by X-ray crystallography, and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand-protein interactions, and identify new potent inhibitors of the Keap1-Nrf2 PPI.

Novel molecular targeting anti-tumor aza-steroid derivative based on lipid toxicity and preparation and application thereof

The invention provides a novel molecular targeting anti-tumor aza-steroid derivative based on lipid toxicity and a preparation method and application thereof, and belongs to the field of chemical medicines. The derivative is a compound as shown in a formula I, or a salt thereof, or a stereoisomer thereof. The compound is low in toxicity or basically non-toxic to normal cells, has an obvious inhibition effect to tumor cell lines, particularly has good lipid toxicity selectivity to tumor cells such as liver cancer, lung cancer and the like in vivo, and has an obvious inhibition effect; meanwhile, the compound can effectively activate SREBP1 and PPAR gamma, inhibit lipid transport MTTP, cause lipid aggregation in tumor cells and cause lipid toxicity of the tumor cells. The compound can be used for treating liver cancer, lung cancer and the like in a molecular targeting manner, is low in toxicity or even non-toxic, and has a good application prospect.

HETEROCYCLIC COMPOUNDS AND USE THEREOF

Disclosed are compounds of formula (I) below or pharmaceutically acceptable salts thereof: in which each of variables R1-R6, L, m, and n is defined herein. Also disclosed are a method for treating an opioid receptor-associated condit

HETEROCYCLIC COMPOUNDS AND USE THEREOF

Disclosed are compounds of formula (I) below or pharmaceutically acceptable salts thereof:in which each of variables R 1 -R 6 , L, m, and n is defined herein. Also disclosed are a method for treating an opioid receptor-associated condition with a compound

A Comparative Assessment Study of Known Small-Molecule Keap1-Nrf2 Protein-Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity

Inhibiting the protein-protein interaction (PPI) between the transcription factor Nrf2 and its repressor protein Keap1 has emerged as a promising strategy to target oxidative stress in diseases, including central nervous system (CNS) disorders. Numerous non-covalent small-molecule Keap1-Nrf2 PPI inhibitors have been reported to date, but many feature suboptimal physicochemical properties for permeating the blood-brain barrier, while others contain problematic structural moieties. Here, we present the first side-by-side assessment of all reported Keap1-Nrf2 PPI inhibitor classes using fluorescence polarization, thermal shift assay, and surface plasmon resonance - and further evaluate the compounds in an NQO1 induction cell assay and in counter tests for nonspecific activities. Surprisingly, half of the compounds were inactive or deviated substantially from reported activities, while we confirm the cross-assay activities for others. Through this study, we have identified the most promising Keap1-Nrf2 inhibitors that can serve as pharmacological probes or starting points for developing CNS-active Keap1 inhibitors.

DIRECT INHIBITORS OF KEAP1-NRF2 INTERACTION AS ANTIOXIDANT INFLAMMATION MODULATORS

A method of identifying compounds as direct inhibitors of Keap1-Nrf2 interaction through high-throughput screening and lead development. The direct inhibitors of Keap1-Nrf2 interaction are more specific and free of various undesirable effects than existing indirect inhibitors, and are potential drug candidates of chemopreventive and therapeutic agents for treatment of various diseases or conditions involving oxidative stress and/or inflammation, including but not limited to cancers, diabetes, Alzheimer's, and Parkinson's. Novel compounds are identified and methods of preventing or treating diseases or conditions related to Keap1-Nrf2 interaction activity by use of the novel compounds identified or compositions containing such compounds are also disclosed.

Pyridinopyrazine compounds and preparation method thereof, and medical application of pyridinopyrazine compounds

The invention relates to the field of pharmaceutical chemistry, particularly a series of pyridinopyrazine compounds (I). The pharmacodynamical test proves that the compounds are used for resisting external oxidation and electrophilic stimulation by activa

Binding mode and structure-activity relationships around direct inhibitors of the Nrf2-Keap1 complex

An X-ray crystal structure of Kelch-like ECH-associated protein (Keap1) co-crystallised with (1S,2R)-2-[(1S)-1-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl) methyl]-1,2,3,4-tetrahydroisoquinolin-2-carbonyl]cyclohexane-1-carboxylic acid (compound (S,R,S)-1 a) was obtained. This X-ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)-1 a, as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently. To dock or not to dock? Nrf2 has become an attractive neuroprotective target, as the Nrf2 pathway provides a natural cell defense mechanism against damage. Targeting its physiological negative modulator Keap1 with small molecules may allow Nrf2 to play its protective role. To this end, an X-ray structure of Keap1 co-crystallised with compound (S,R,S)-1 a was obtained, elucidating its binding mode, which in turn helped to drive the drug design process.

Discovery of a small-molecule inhibitor and cellular probe of Keap1-Nrf2 protein-protein interaction

A high-throughput screen (HTS) of the MLPCN library using a homogenous fluorescence polarization assay identified a small molecule as a first-in-class direct inhibitor of Keap1-Nrf2 protein-protein interaction. The HTS hit has three chiral centers; a combination of flash and chiral chromatographic separation demonstrated that Keap1-binding activity resides predominantly in one stereoisomer (SRS)-5 designated as ML334 (LH601A), which is at least 100× more potent than the other stereoisomers. The stereochemistry of the four cis isomers was assigned using X-ray crystallography and confirmed using stereospecific synthesis. (SRS)-5 is functionally active in both an ARE gene reporter assay and an Nrf2 nuclear translocation assay. The stereospecific nature of binding between (SRS)-5 and Keap1 as well as the preliminary but tractable structure-activity relationships support its use as a lead for our ongoing optimization.