99548-55-7

Usage

Chemical Properties

off-white powder

InChI:InChI=1/C9H9BrO2/c1-6-5-7(10)3-4-8(6)9(11)12-2/h3-5H,1-2H3

Upstream product

• 67-56-1 methanol 
• 68837-59-2 4-bromo-2-methylbenzoic acid 
• 67832-11-5 4-bromo-2-methylbenzonitrile 
• 77-78-1 dimethyl sulfate 
• 21900-45-8 4-bromo-2-methylbenzoyl chloride 
• 74-88-4 methyl iodide 
• 18107-18-1 diazomethyl-trimethyl-silane 

Downstream Products

• 856167-33-4 4-bromo-2-methylbenzohydrazide 
• 190367-35-2 4-Cyclohexyl-2-methyl-benzoic acid methyl ester 
• 190367-36-3 methyl 4-cyclobutyl-2-methylbenzoate 
• 190367-32-9 4-isopropyl-2-methylbenzoic acid methyl ester 
• 495388-46-0 4-((E)-3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-Heptadecafluoro-dec-1-enyl)-2-methyl-benzoic acid methyl ester 
• 819851-96-2 4-(benzyl-methyl-amino)-2-methyl-benzoic acid methyl ester 
• 74733-23-6 methyl 4-formyl-2-methyl-benzoate 
• 139988-46-8 diethyl 2-(S)-[5-methylamino-2,3-dihydro-1-oxo-2(1H)-isoindolyl]glutarate 
• 819851-97-3 2-methyl-4-methylamino-benzoic acid methyl ester 
• 819851-98-4 methyl 4-(N-methyl-N-trifluoroacetylamino)-2-methylbenzoate 
• 819851-99-5 2-Bromomethyl-4-[methyl-(2,2,2-trifluoro-acetyl)-amino]-benzoic acid methyl ester 
• 620989-04-0 4-(4-Methoxy-phenoxy)-2-methyl-benzoic Acid Methyl Ester 
• 530091-81-7 methyl 2-methyl-4-pyrrolidin-1-ylbenzoate 
• 525362-07-6 methyl 2-methyl-4-(4,4,5 ,5-tetramethyl-1,3 ,2-dioxaborolan-2-yl)benzoate 

Relevant academic research and scientific papers

CC-90009: A Cereblon E3 Ligase Modulating Drug That Promotes Selective Degradation of GSPT1 for the Treatment of Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is marked by significant unmet clinical need due to both poor survival and high relapse rates where long-term disease control for most patients with relapsed or refractory AML remain dismal. Inspired to bring novel therapeutic options to these patients, we envisioned protein degradation as a potential therapeutic approach for the treatment of AML. Following this course, we discovered and pioneered a novel mechanism of action which culminated in the discovery of CC-90009. CC-90009 represents a novel protein degrader and the first cereblon E3 ligase modulating drug to enter clinical development that specifically targets GSPT1 (G1 to S phase transition 1) for proteasomal degradation. This manuscript briefly summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and efficacy data for CC-90009, which is currently in phase 1 clinical development.

PROCESSES FOR PREPARING 2-(4-CHLOROPHENYL)-N-((2-(2,6-DIOXOPIPERIDIN-3-YL)-1-OXOISOINDOLIN-5-YL)METHYL)-2,2-DIFLUOROACETAMIDE

Provided herein are processes for preparing 2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide.

Highly selective electroreductive linear dimerization of electron-deficient vinylarenes

A direct electroreductive dimerization of electron-deficient vinylarenes for the synthesis of 1,4-diarylbutane has been developed using a simple undivided cell with inexpensive carbon electrodes at room temperature. The control and deuterium-labeling experiments of electroreductive dimerization suggest that the hydrogen source comes from the solvent CH3CN. This protocol provides a mild and efficient route for the construction of C–C bond in moderate to good yields with high regioselectivity and broad substrate scope.

Discovery of 3-Pyridyl Isoindolin-1-one Derivatives as Potent, Selective, and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors

Aldosterone synthase (CYP11B2) inhibitors have been explored in recent years as an alternative therapeutic option to mineralocorticoid receptor (MR) antagonists to reduce elevated aldosterone levels, which are associated with deleterious effects on various organ systems including the heart, vasculature, kidney, and central nervous system (CNS). A benzamide pyridine hit derived from a focused screen was successfully developed into a series of potent and selective 3-pyridyl isoindolin-1-ones CYP11B2 inhibitors. Our systematic structure-activity relationship study enabled us to identify unique structural features that result in high selectivity against the closely homologous cortisol synthase (CYP11B1). We evaluated advanced lead molecules, exemplified by compound 52, in an in vivo cynomolgus monkey acute adrenocorticotropic hormone (ACTH) challenge model and demonstrated a superior 100-fold in vivo selectivity against CYP11B1.

Preparation method of methyl 4-bromoacetyl-2-methylbenzoate

The invention provides a preparation method of methyl 4-bromoacetyl-2-methylbenzoate. The preparation method comprises the following steps: (1) dissolving 4-bromo-2-methylbenzoic acid in methanol, andperforming an esterification reaction under the catalytic action of sulfuric acid so as to produce a first intermediate compound; (2) performing a reaction between the first intermediate compound with potassium vinyl fluoroborate or vinyl boronic acid under the catalytic action of palladium so as to obtain a second intermediate compound; and (3) performing an alpha-halogenated ketone synthesis reaction on the second intermediate compound under the action of a halogenating reagent so as to obtain the methyl 4-bromoacetyl-2-methylbenzoate. The preparation method has the advantages of low raw material cost, a short route, mild reaction conditions, simple requirements for equipment and experimental conditions, large-scale amplification synthesis and a high application value.

BENZAZEPINE DERIVATIVE, PREPARATION METHOD, PHARMACEUTICAL COMPOSITION AND USE THEREOF

Disclosed are a benzazepine derivative, a preparation method, a pharmaceutical composition and the use thereof. A compound as shown in formula (I) of the present invention, and an isomer, a prodrug, a stable isotope derivative or a pharmaceutically acceptable salt thereof have the following structure. The benzazepine derivative of the present invention has a good regulation effect on the TLR family and the related signalling pathway, and in particular, has a good regulation effect on TLR8, can effectively treat, relieve and/or prevent various diseases mediated by TLR family and the TLR-related signalling pathway, and in particular, can effectively treat, relieve and/or prevent various diseases mediated by TLR8, such as cancers, autoimmune diseases, infections, inflammations, transplantation rejections, graft-versus-host diseases, etc.

Protein Degradation via CRL4CRBN Ubiquitin Ligase: Discovery and Structure-Activity Relationships of Novel Glutarimide Analogs That Promote Degradation of Aiolos and/or GSPT1

We previously disclosed the identification of cereblon modulator 3 (CC-885), with potent antitumor activity mediated through the degradation of GSPT1. We describe herein the structure-activity relationships for analogs of 3 with exploration of the structurally related dioxoisoindoline class. The observed activity of protein degradation could in part be rationalized through docking into the previously disclosed 3-CRBN-GSPT1 cocrystal ternary complex. For SAR that could not be rationalized through the cocrystal complex, we sought to predict SAR through a QSAR model developed in house. Through these analyses, selective protein degradation could be achieved between the two proteins of interest, GSPT1 and Aiolos.

BICYCLIC COMPOUNDS USEFUL AS GPR120 MODULATORS

Provided herein are compounds, compositions including them, and methods of modulating GPR120 activity and treating diseases mediated by GPR120 by administering such compounds and compositions.

Method for preparing 2-methyl-4-formaldoxime methyl benzoate

The invention discloses a method for preparing 2-methyl-4-formaldoxime methyl benzoate. The method comprises the following steps: performing acylating chlorination on 2-methyl-4-bromobenzoic acid, carrying out methanol esterification and cyano substitution, and then performing nucleophilic addition elimination with hydroxylamine hydrochloride under alkaline conditions to obtain a target product. The method has the advantages that the process route is simple; reaction conditions are mild; the product yield is high; the total yield reaches 61 percent; the product quality is high; the appearance is white solid; the purity reaches 99.2 percent.

METHODS FOR TREATING CANCER AND THE USE OF BIOMARKERS AS A PREDICTOR OF CLINICAL SENSITIVITY TO THERAPIES

A method of identifying a subject having cancer who is likely to be responsive to a treatment compound, comprising administering the treatment compound to the subject having the cancer; obtaining a sample from the subject; determining the level of a biomarker in the sample from the subject; and diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject changes as compared to a reference level of the biomarker; wherein the treatment compound is a compound of Formula I: