1356483-75-4

Usage

Uses

Used in Pharmaceutical Industry:
(5-Bromo-2-Nitro-Phenyl)-Cyclopropyl-Amine is used as a building block for the synthesis of various pharmaceuticals. Its cyclopropyl-amine group and functionalized phenyl ring contribute to the development of new drugs with improved efficacy and selectivity in treating different medical conditions.
Used in Agrochemical Industry:
In the agrochemical sector, (5-Bromo-2-Nitro-Phenyl)-Cyclopropyl-Amine serves as a key intermediate for the synthesis of novel agrochemicals. Its unique structural features allow for the creation of new molecules with enhanced pesticidal, herbicidal, or fungicidal properties, contributing to more effective crop protection strategies.
Used as a Reagent in Chemical Reactions:
(5-Bromo-2-Nitro-Phenyl)-Cyclopropyl-Amine is also utilized as a reagent in various chemical reactions, facilitating the synthesis of complex organic molecules. Its presence can enhance the reaction conditions and improve the overall yield of the desired products.
Used for Derivatization and Modification:
(5-Bromo-2-Nitro-Phenyl)-Cyclopropyl-Amine's bromo and nitro functional groups make it an ideal candidate for further derivatization and modification. This allows for the creation of new chemical entities with potentially beneficial properties, expanding the scope of its applications in both the pharmaceutical and agrochemical industries.

Upstream product

• 321-23-3 4-bromo-2-fluoronitrobenzene 
• 765-30-0 Cyclopropylamine 

Downstream Products

• 1356483-77-6 5-bromo-N¹-cyclopropylbenzene-1,2-diamine 

Relevant academic research and scientific papers

Structure-Based Discovery and Development of a Series of Potent and Selective Bromodomain and Extra-Terminal Protein Inhibitors

BRD4 has recently emerged as a promising drug target. Therefore, identifying novel inhibitors with distinct properties could enrich their use in anticancer treatment. Guided by the cocrystal structure of hit compound 4 harboring a five-membered-ring linker motif, we quickly identified lead compound 7, which exhibited good antitumor effects in an MM.1S xenograft model by oral administration. Encouraged by its high potency and interesting scaffold, we performed further lead optimization to generate a novel potent series of bromodomain and extra-terminal (BET) inhibitors with a (1,2,4-triazol-5-yl)-3,4-dihydroquinoxalin-2(1H)-one structure. Among them, compound 19 was found to have the best balance of activity, stability, and antitumor efficacy. After confirming its low brain penetration, we conducted comprehensive preclinical studies, including a multiple-species pharmacokinetics profile, extensive cellular mechanism studies, hERG assay, and in vivo antitumor growth effect testing, and we found that compound 19 is a potential BET protein drug candidate for the treatment of cancer.

Structure-based optimization of a series of selective BET inhibitors containing aniline or indoline groups

Recently, several kinase inhibitors were found to also inhibit bromodomains, providing a new strategy for the discovery of bromodomain inhibitors. Along this line, starting from PLK1-BRD4 dual inhibitor BI-2536, we discovered a new series of dihydroquinoxalin-2(1H)-one with aniline and indoline WPF binders as selective BRD4 inhibitors. They showed better BRD4-BD1 potency and negligible PLK1 kinase activity comparing with BI-2536. Additionally, dihydroquinoxalin-2(1H)-ones containing indoline group showed profound activities in molecular and cellular based assays. Throughout the study, compounds 9, 28 and 37 showed significant inhibitory activity for c-Myc or PD-L1 protein expression and mRNA transcription both at concentration of 0.2 and 1 μM. Compound 9 was found possessing the best balance of binding affinity, in vitro metabolic stability and in vivo pharmacokinetic properties. Therefore, it was selected for in vivo pharmacological study. By using MM.1S cell derived xenograft model, we confirmed compound 9 showed comparable in vivo tumor inhibition to phase II investigation drug I-BET762, which, together with the novel WPF binder, further indicated the utility of this series of BRD4 inhibitors.

Compound with multi-target inhibition effect, composition, functional molecule and application of compound

The invention relates to a compound with a multi-target inhibition effect, a composition, a functional molecule and application of the compound. The compound has a structure shown in a formula (I), wherein K in the formula is as shown in the specification. The compound has an inhibition effect on BET and kinase double targets and can simultaneously act on different signal channels of tumor cell growth to achieve a better treatment effect.

THYROID HORMONE RECEPTOR BETA AGONIST COMPOUNDS

Provided herein are compounds, preferably thyroid hormone receptor beta (THR beta) agonist compounds, compositions thereof, and methods of their preparation, and methods of agonizing THR beta and methods for treating disorders mediated by THR beta.

KINASE INHIBITOR COMPOUNDS AND COMPOSITIONS AND METHODS OF USE

Disclosed are kinase inhibitor compounds having the following structure: (I), or a stereoisomer, pharmaceutically acceptable salt, oxide, or solvate thereof, where R1, R2, R3,R4, R5, R6, N-Ar, X, Y, Z, and AA are as defined herein. Also disclosed are compositions containing the kinase inhibitor compounds, methods of inhibiting activity of a kinase in a cell, methods of increasing cell proliferation in a population of pancreatic beta cells, methods of treating a subject for a condition associated with insufficient insulin secretion, and methods of treating a subject for a neurological disorder.

KINASE INHIBITOR COMPOUNDS AND COMPOSITIONS AND METHODS OF USE

Disclosed herein are kinase inhibitor compounds having structure (I), or a stereoisomer, pharmaceutically acceptable salt, oxide, or solvate thereof, where R1, R2, R3, R4, R5, R6, R7, X, Y, Z, and (AA) are as defined herein. Also disclosed are compositions containing the kinase inhibitor compounds, methods of inhibiting activity of a kinase in a cell, methods of increasing cell proliferation in a population of pancreatic beta cells, methods of treating a subject for a condition associated with insufficient insulin secretion, and methods of treating a subject for a neurological disorder.

DIHYDROQUINOXALINE BROMODOMAIN RECOGNITION PROTEIN INHIBITOR, PREPARATION METHOD AND USE THEREOF

The present invention relates to dihydroquinoxaline bromodomain recognition protein inhibitor, preparation method and use thereof. The inhibitor of the present invention is compound represented by general formula (I), or stereoisomer, pharmaceutically acceptable salt, prodrug, solvate, hydrate and crystal form thereof. The definition of each substituent is as described in the description and claims. The compound represented by general formula (I) of the present invention may inhibit bromodomain recognition protein and may be used for preparing medicament which regulates the apparent state of cells and treats series of diseases and symptoms which are mediated by the bromodomain recognition protein.

Discovery of a series of dihydroquinoxalin-2(1H)-ones as selective BET inhibitors from a dual PLK1-BRD4 inhibitor

Recent years have seen much effort to discover new chemotypes of BRD4 inhibitors. Interestingly, some kinase inhibitors have been demonstrated to be potent bromodomain inhibitors, especially the PLK1 inhibitor BI-2536 and the JAK2 inhibitor TG101209, which can bind to BRD4 with IC50 values of 0.025 μM and 0.13 μM, respectively. Although the concept of dual inhibition is intriguing, selective BRD4 inhibitors are preferred as they may diminish off-target effects and provide more flexibility in anticancer drug combination therapy. Inspired by BI-2536, we designed and prepared a series of dihydroquinoxalin-2(1H)-one derivatives as selective bromodomain inhibitors. We found compound 54 had slightly higher activity than (+)-JQ1 in the fluorescence anisotropy assay and potent antiproliferative cellular activity in the MM.1S cell line. We have successfully solved the cocrystal structure of 52 in complex with BRD4-BD1, providing a solid structural basis for the binding mode of compounds of this series. Compound 54 exhibited high selectivity over most non-BET subfamily members and did not show bioactivity towards the PLK1 kinase at 10 or 1 μM. From in vivo studies, compound 54 demonstrated a good PK profile, and the results from in vivo pharmacological studies clearly showed the efficacy of 54 in the mouse MM.1S xenograft model.

HEPARAN SULFATE BIOSYNTHESIS INHIBITORS FOR THE TREATMENT OF DISEASES

Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or conditions in need of inhibition of heparan sulfate biosynthesis.

ALDOSTERONE SYNTHASE INHIBITORS

The invention involves compounds of structural Formula (I) and the pharmaceutically acceptable salts thereof. The compounds of the invention are effective at selectively inhibiting CYP11B2, and are therefore useful for the treatment or prophylaxis of disorders that are associated with elevated aldosterone levels, including, but not limited to, hypertension and heart failure.