1639042-39-9

Usage

Uses

Used in Pharmaceutical Industry:
(E)-methyl 3-(3,5-difluoro-4-formylphenyl)acrylate is used as a key intermediate in the synthesis of pharmaceuticals for its ability to be incorporated into the molecular structures of potential drug candidates. Its reactivity and unique functional groups facilitate the creation of new compounds with therapeutic properties.
Used in Agrochemical Industry:
In the agrochemical sector, (E)-methyl 3-(3,5-difluoro-4-formylphenyl)acrylate is employed as a reagent in the development of novel agrochemicals. Its chemical properties allow for the synthesis of molecules with pesticidal or herbicidal activities, contributing to the advancement of crop protection strategies.
Used in Materials Science:
(E)-methyl 3-(3,5-difluoro-4-formylphenyl)acrylate is utilized as a component in the production of advanced materials. Its incorporation into polymers and other materials can enhance their properties, such as stability, durability, or specific functional characteristics, making it a valuable asset in material development.
Used in Organic Synthesis:
As a building block in organic synthesis, (E)-methyl 3-(3,5-difluoro-4-formylphenyl)acrylate is used for the preparation of various functionalized molecules across different industries. Its unique structure and reactivity make it an essential component in the synthesis of specialty chemicals, dyes, and other organic compounds.

Upstream product

• 1206630-22-9 5-bromo-2-(diethoxymethyl)-1,3-difluorobenzene 
• 537013-51-7 4-bromo-2,6-difluorobenzaldehyde 
• 292638-85-8 acrylic acid methyl ester 

Downstream Products

• 1639042-08-2 (E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methyl-propyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid 

Relevant academic research and scientific papers

Synthesis method of (E)-methyl ester 3-(3,5-difluoro-4-formyl phenyl)acrylic acid

The invention provides a synthesis method of (E)-methyl ester 3-(3,5-difluoro-4-formyl phenyl)acrylic acid, and relates to the field of organic synthesis. The method comprises the following steps: (1) aldehyde group protection: reacting a compound 1, ammonium chloride and alcohol to obtain a compound 2, wherein the alcohol is selected from monohydric alcohol or dihydric alcohol; (2) introducing formyl: reacting the compound 2 serving as a raw material with an organic metal reagent in an organic solvent, and then adding N,N-dimethylformamide for reaction to obtain a compound 3; (3) Wittig-Horner reaction: adding alkali and a compound containing a phosphonate group into the compound 3, and reacting to obtain a compound 4; and (4) deprotection reaction: adding a compound containing a sulfonic acid group and water into the compound 4, and reacting to obtain the product. The synthesis method does not use a noble metal catalyst, so that the cost is obviously reduced; and the product prepared by the synthesis method is high in yield, high in purity, environment-friendly, high in safety and suitable for industrial production, and has a good application prospect.

ESTROGEN RECEPTOR-MODULATING COMPOUNDS

Described herein are compounds that are estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.

Tricyclic Indazoles - A Novel Class of Selective Estrogen Receptor Degrader Antagonists

Herein, we report the identification and synthesis of a series of tricyclic indazoles as a novel class of selective estrogen receptor degrader antagonists. Replacement of a phenol, present in our previously reported tetrahydroisoquinoline scaffold, with an indazole group led to the removal of a reactive metabolite signal in an in vitro glutathione trapping assay. Further optimization, guided by X-ray crystal structures and NMR conformational work, varied the alkyl side chain and pendant aryl group and resulted in compounds with low turnover in human hepatocytes and enhanced chemical stability. Compound 9 was profiled as a representative of the series in terms of pharmacology and demonstrated the desired estrogen receptor α degrader-antagonist profile and demonstrated activity in a xenograft model of breast cancer.

BENZOPIPERIDINE DERIVATIVE, PREPARATION METHOD THEREOF AND MEDICAL USE THEREOF

The present invention relates to a benzopiperidine derivative, a preparation method thereof and a medical use thereof. In particular, the present invention relates to a benzopiperidine derivative as shown by general formula (I), a preparation method thereof and a pharmaceutical composition containing the derivative, as well as a use thereof as an estrogen receptor modulator in the prevention and/or treatment of estrogen receptor-mediated or dependent diseases or conditions. Preferably, the disease is breast cancer. The substituents in the general formula (I) are the same as those defined in the description.

3-substituted acrylic acid compound as well as preparation method and application thereof

The invention provides a 3-substituted acrylic acid compound as well as a preparation method and application thereof and in particular relates to a 3-substituted acrylic acid compound, a stereoisomer,a pro-drug, a hydrate or pharmaceutically acceptable salt or ester thereof, and a pharmaceutical composition thereof as well as a preparation method and application thereof. The compound provided bythe invention can inhibit activity of an estrogen receptor, regulate expression level of the estrogen receptor down or induce degradation of the estrogen receptor and can be used for preventing or treating diseases related to overactivity of the estrogen receptor, especially estrogen receptor positive (ER+) drug-resistant diseases (such as breast cancer producing drug resistance to anti-estrogen therapy).

ACRYLIC ACID DERIVATIVE, PREPARATION METHOD AND USE IN MEDICINE THEREOF

The present invention relates to an acrylic acid derivative as shown in general formula (I), a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, the preparation method thereof, a pharmaceutical composition containing same, and the use thereof as therapeutic agents, in particular as selective estrogen receptor degraders (SERD), wherein the substituents of general formula (I) are the same as those defined in the description.

Tetracyclic compound serving as selective estrogen receptor regulating agent and application thereof

The invention belongs to the field of medical chemistry, relates to a tetracyclic compound serving as a selective estrogen receptor regulating agent and application thereof, and particularly providesa compound shown as a formula I or an isomer, a pharmaceutically-acceptable salt, a solvate, a crystal or a prodrug thereof, preparation methods thereof, pharmaceutical compositions containing the compounds and application of the compounds or the compositions to the treatment and/or prevention of estrogen receptor related disease. The compound disclosed by the invention has more superior antineoplastic activity, and is expected to be a breast cancer treatment agent. The formula I is shown in the description.

ESTROGEN RECEPTOR MODULATORS

Compounds of Formula (I) are estrogen receptor alpha modulators, where the variables in Formula (I) are described in the disclosure. Such compounds, as well as pharmaceutically acceptable salts and compositions thereof, are useful for treating diseases or conditions that are estrogen receptor alpha dependent and/or estrogen receptor alpha mediated, including conditions characterized by excessive cellular proliferation, such as breast cancer.

Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist

The discovery of an orally bioavailable selective estrogen receptor downregulator (SERD) with equivalent potency and preclinical pharmacology to the intramuscular SERD fulvestrant is described. A directed screen identified the 1-aryl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole motif as a novel, druglike ER ligand. Aided by crystal structures of novel ligands bound to an ER construct, medicinal chemistry iterations led to (E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid (30b, AZD9496), a clinical candidate with high oral bioavailability across preclinical species that is currently being evaluated in phase I clinical trials for the treatment of advanced estrogen receptor (ER) positive breast cancer.

CHEMICAL COMPOUNDS

The invention concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R1 to R5 have any of the meanings defined hereinbefore in the description: processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.