103796-24-3

Upstream product

• 2735-04-8 2,4-Dimethoxyaniline 
• 23042-75-3 N-(2,4-dimethoxyphenyl)acetamide 
• 75-36-5 acetyl chloride 
• 102877-53-2 1-(2-hydroxy-4-methoxy-5-nitrophenyl)ethanone 
• 552-41-0 1-(2-hydroxy-4-methoxyphenyl)ethanone 
• 89-84-9 2',4'-dihydroxy-4-acetophenone 
• 93483-92-2 1-(5-amino-2-hydroxy-4-methoxyphenyl)ethanone 
• 108-24-7 acetic anhydride 

Downstream Products

• 113184-47-7 5'-acetylamino-2'-hydroxy-4'-methoxy-3,4-methylenedioxy-trans-chalcone 
• 111935-97-8 acetic acid-[4-hydroxy-2-methoxy-5-(2-methoxy-trans-cinnamoyl)-anilide] 
• 1832671-96-1 5-bromo-2-methoxy-N-(6-methoxy-3-methylbenzo[d]isoxazol-5-yl)benzenesulfonamide 
• 101730-64-7 6-amino-2-(3,4-dimethoxy-phenyl)-7-methoxy-chroman-4-one 
• 109395-47-3 6-amino-7-methoxy-2-(2-methoxy-phenyl)-chroman-4-one 

Relevant academic research and scientific papers

Synthesis, evaluation and in silico studies of novel BRD4 bromodomain inhibitors bearing a benzo[d]isoxazol scaffold

Abstract: The BRD4 protein is associated with various diseases, which has been an attractive target for the treatment of cancer and inflammation. This paper is a follow-up to our previous studies, in which we report the structure-based design, synthesis, and evaluation of a new class of small-molecule BRD4 bromodomain inhibitors bearing a benzo[d]isoxazol scaffold. The SARs focused on exploration of the 2′ or 3′ position to afford novel inhibitors that may avoid potential metabolically unstable site. The most potent inhibitor 13f exhibited high binding affinity to BRD4(1) with a ΔTm value of 7.8 °C as evaluated in thermal shift assay (TSA). The potent activity was also demonstrated by a peptide competition assay with an IC50 value of 0.21?μM. The docking studies revealed the binding mode of the compounds with the active site of BRD4(1). In addition, in silico predictions indicated that these compounds possessed good drug-likeness and pharmacokinetic profile. Graphic abstract: This paper is a follow-up to our previous studies, in which we report the structure-based design,synthesis, and evaluation of a new class of small-molecule BRD4 bromodomain inhibitors bearing a benzo[d]isoxazolscaffold.[Figure not available: see fulltext.].

Structure-Based Discovery and Optimization of Benzo [d] isoxazole Derivatives as Potent and Selective BET Inhibitors for Potential Treatment of Castration-Resistant Prostate Cancer (CRPC)

The bromodomain and extra-terminal (BET) family proteins have gained increasing interest as drug targets for treatment of castration-resistant prostate cancer (CRPC). Here, we describe the design, optimization, and evaluation of benzo[d]isoxazole-containing compounds as potent BET bromodomain inhibitors. Cocrystal structures of the representative inhibitors in complex with BRD4(1) provided solid structural basis for compound optimization. The two most potent compounds, 6i (Y06036) and 7m (Y06137), bound to the BRD4(1) bromodomain with Kd values of 82 and 81 nM, respectively. They also exhibited high selectivity over other non-BET subfamily members. The compounds potently inhibited cell growth, colony formation, and the expression of AR, AR regulated genes, and MYC in prostate cancer cell lines. Compounds 6i and 7m also demonstrated therapeutic effects in a C4-2B CRPC xenograft tumor model in mice. These potent and selective BET inhibitors represent a new class of compounds for the development of potential therapeutics against CRPC.

A kind of benzo [d] different wicked zuozuo apperception compound and use thereof

The invention relates to the technical field of chemical medicine, and particularly discloses a benzo[d]isoxazole compound shown as a general formula (A) and application thereof. The compound can effectively inhibit bromodomain of BET family proteins so as to block interaction between the BET family proteins and chromatin histone to adjust genetic transcription, cause changing of a downstream signal path and exert important influence on various diseases, so that the compound and a combination thereof can be used for preparing medicine for treating or preventing diseases like tumorigenesis, inflammation, viral infection, cell proliferation disorder, autoimmune diseases and septicemia.

COMPOUNDS FOR THE TREATMENT OF AMYLOID-ASSOCIATED DISEASES

This invention provides novel compounds of formulae (I) or (II) or a stereoisomer, enantiomer, racemic, or tautomer thereof, (I) (II) wherein the substituents are as defined in the specification. The present invention also relates to the novel compounds for use as a medicine, more in particular for the prevention or treatment of amyloid-related diseases, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, disorders characterized by cytotoxic α-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such amyloid-related diseases. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds.