113181-02-5

Basic information

• Product Name: (2S)-3-BroMo-N-[4-cyano-3-(trifluoroMethyl)phenyl]-2-hydroxy-2-Methyl-propanaMide
• Synonyms: (2S)-3-BroMo-N-[4-cyano-3-(trifluoroMethyl)phenyl]-2-hydroxy-2-Methyl-propanaMide
• CAS NO: 113181-02-5
• Molecular Formula: C₁₂H₁₀BrF₃N₂O₂
• Molecular Weight: 351.1192096
• Product Categories: Aromatics, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 113181-02-5.mol

Chemical Properties

• Appearance: /
• Storage Temp.: Refrigerator
• Solubility: Acetone (Slightly), Chloroform (Slightly), Methanol (Slightly)
• CAS DataBase Reference: (2S)-3-BroMo-N-[4-cyano-3-(trifluoroMethyl)phenyl]-2-hydroxy-2-Methyl-propanaMide(CAS DataBase Reference)
• NIST Chemistry Reference: (2S)-3-BroMo-N-[4-cyano-3-(trifluoroMethyl)phenyl]-2-hydroxy-2-Methyl-propanaMide(113181-02-5)
• EPA Substance Registry System: (2S)-3-BroMo-N-[4-cyano-3-(trifluoroMethyl)phenyl]-2-hydroxy-2-Methyl-propanaMide(113181-02-5)

Safety Data

• Hazardous Substances Data: 113181-02-5(Hazardous Substances Data)

Usage

Uses

1. Used in Pharmaceutical Synthesis:
(2S)-3-Bromo-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methyl-propanamide is used as a reactant for the preparation of hydroxy(phenylthio)propionanilides. These compounds serve as affinity ligands for the androstane receptor, which plays a crucial role in the development and function of the reproductive, nervous, and urinary systems. The androstane receptor is a target for various therapeutic applications, including the treatment of hormone-related disorders and certain cancers.
2. Used in Chemical Research:
As a complex organic molecule with unique structural features, (2S)-3-Bromo-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methyl-propanamide is also employed in chemical research. It can be used to study the effects of different functional groups on the reactivity and stability of molecules, as well as to explore new synthetic pathways and methodologies in organic chemistry.
3. Used in the Synthesis of Biochemical Compounds:
The compound's unique structure and reactivity make it a valuable building block in the synthesis of various biochemical compounds. It can be used to create new molecules with potential applications in the fields of biochemistry and molecular biology, such as enzyme inhibitors, receptor agonists or antagonists, and other bioactive molecules.

Upstream product

• 654-70-6 4-amino-2-trifluoromethylbenzonitrile 
• 106089-20-7 (S)-(-)-3-bromo-2-hydroxy-2-methylpropanoic acid 
• 1010729-05-1 C₄H₆BrClO₂ 
• 927203-28-9 3-bromomethyl-3-methyl-tetrahydro-pyrrolo[2,1-c][1,4]oxazine-1,4-dione 

Downstream Products

• 1132656-73-5 (R)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide 
• 2031161-35-8 (2R)-N-[4-cyano-3-(trifluoromethyl)phenyl]-3-(5-fluoro-1H-indol-1-yl)-2-hydroxy-2-methylpropanamide 
• 1019972-88-3 (R)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-methyloxirane-2-carboxamide 
• 261904-44-3 N₁-[4-cyano-3-(trifluoromethyl)phenyl]-(2S)-3-[(4-aminophenyl)sulfanyl]-2-hydroxy-2-methylpropanamide 

Relevant articles and documents

Pyrazol-1-yl-propanamides as SARD and Pan-Antagonists for the Treatment of Enzalutamide-Resistant Prostate Cancer

We report herein the design, synthesis, and pharmacological characterization of a library of novel aryl pyrazol-1-yl-propanamides as selective androgen receptor degraders (SARDs) and pan-Antagonists that exert broad-scope AR antagonism. Pharmacological ev

SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF

This invention is directed to selective androgen receptor degrader (SARD) compounds including heterocyclic rings and pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedys disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

Synthetic method of alpha-hydroxypropanamide derivatives with optical activity

The invention discloses a synthetic method of alpha-hydroxypropanamide derivatives with optical activity and belongs to the field of organic synthesis. Proline taken as a chiral auxiliary, as well asmethacryloyl chloride, is subjected to acylation, bromination and chiral auxiliary removal, a product and 4-cyano-3-trifluoromethylaniline are subjected to nucleophilic substitution, and 3-bromo-2-hydroxy-2-methyl-N-[(4-cyano-3-trifluoromethyl)phenyl]propanamide is obtained and subjected to nucleophilic substitution with 4-cyanophenol, and the compound 3-(4-cyanophenoxy)-N-[4-cyano-3-(trifluoromethylphenyl]-2-hydroxy-2-methylpropanamide with optical activity is prepared. 3-bromo-2-hydroxy-2-methyl propionic acid and 4-nitro-3-trifluoromethylaniline are subjected to aminolysis, a product is subjected to nucleophilic substitution with paracetamol, and the compound 3-(4-acetoxyphenoxy)-N-[4-nitro-3-(trifluoromethylphenyl]-2-hydroxy-2-methylpropanamide with optical activity is prepared. The efficient synthetic method of the alpha-hydroxypropanamide derivatives with optical activity is provided.

New Generation of Selective Androgen Receptor Degraders: Our Initial Design, Synthesis, and Biological Evaluation of New Compounds with Enzalutamide-Resistant Prostate Cancer Activity

In our effort to find small-molecule treatments of advanced prostate cancers (PCs), a novel series of indolyl and indolinyl propanamides (series II and III) were discovered as selective androgen receptor degraders (SARDs). Initial studies of androgen receptor (AR) antagonist (1) and agonist (2) propanamides yielded a tertiary aniline (3) with novel SARD activity but poor metabolic stability. Cyclization to II and III produced submicromolar AR antagonism and protein degradation selective to AR and AR splice variant (AR SV). II and III maintained potency against enzalutamide-resistant (Enz-R) mutant ARs and PC cells and were efficacious in Enz-R xenografts, suggesting their potential to treat advanced PCs. Design, synthesis, and biological activity of novel SARDs that could potentially be used for the treatment of a wide spectrum of PCs including castration-resistant, Enz-R, and/or AR SV-dependent advanced PCs that are often untreatable with known hormone therapies are discussed.

SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF

This invention is directed to pyrrole, pyrazole, imidazole, triazole, and morpholine based selective androgen receptor degrader (SARD) compounds including heterocyclic anilide rings and their synthetic precursors, R-isomers, and non-hydroxylated and/or non-chiral propanamides, and pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF

This invention provides novel indole, indazole, benzimidazole, indoline, quinolone, isoquinoline, and carbazole selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other hyper androgenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic and/or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

A METHOD OF TREATING ANDROGEN RECEPTOR (AR)-POSITIVE BREAST CANCERS WITH SELECTIVE ANDROGEN RECEPTOR MODULATOR (SARMS)

This invention relates to the treatment of androgen receptor-positive breast cancer in a subject, for example a female subject. Accordingly, this invention provides methods of: a) treating a subject suffering from breast cancer; b) treating a subject suffering from metastatic breast cancer; c) treating a subject suffering from refractory breast cancer; d) treating a subject suffering from AR-positive breast cancer; e) treating a subject suffering from AR-positive refractory breast cancer; f) treating a subject suffering from AR-positive metastatic breast cancer; g) treating a subject suffering from AR-positive and ER-positive breast cancer; h) treating a subject suffering from triple negative breast cancer; i) treating a subject suffering from advanced breast cancer; j) treating a subject suffering from breast cancer that has failed SERM (tamoxifen, toremifene), aromatase inhibitor, trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, exemestane (Aromasin), bevacizumab (Avastin), and/or fulvestrant treatments; k) treating, preventing, suppressing or inhibiting metastasis in a subject suffering from breast cancer; 1) prolonging survival of a subject with breast cancer, and/or m) prolonging the progression-free survival of a subject with breast cancer; comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound, comprising administering to the subject a therapeutically effective amount of a SARM compound of this invention.

Synthesis and biological activity of ferrocenyl derivatives of the non-steroidal antiandrogens flutamide and bicalutamide

A series of ferrocenyl derivatives of the two non steroidal antiandrogens flutamide and bicalutamide have been prepared. Ferrocenyl bicalutamide complexes were initially synthesized in their racemic forms, and subsequently prepared as pure (R) and (S) enantiomers, and their structure was determined by X-ray crystallography. Most of the complexes retain a modest affinity for the androgen receptor and show an antiproliferative effect on both hormone-dependent (LNCaP) and -independent (PC-3) prostate cancer cells. Ferrocenyl derivatives of bicalutamide are the most cytotoxic (IC50 values on PC-3 around 15 μM); however, they are less potent than the ferrocenyl derivatives of ethynyltestosterone or nilutamide (IC50 around 5 μM).

Chiral nonsteroidal affinity ligands for the androgen receptor. 1. Bicalutamide analogues bearing electrophilic groups in the B aromatic ring

A series of chiral analogues of bicalutamide bearing electrophilic groups (isothiocyanate, N-chloroacetyl, and N-bromoacetyl) on aromatic ring B of the parent molecule were synthesized. These compounds were designed as affinity ligands for the androgen receptor (AR). We prepared the (R)- and (S)-optical isomers of these compounds as pure enantiomers. The AR binding affinities of these compounds were measured in a competitive binding assay with the radiolabeled high-affinity AR ligand, [3H]mibolerone. In accordance with our previous results for the enantiomers of bicalutamide, we found that all (R)-isomers demonstrated much higher binding affinity to the AR as compared to their corresponding (S)-isomers. The para-substituted affinity ligands in ring B bound the AR with higher affinities than the corresponding metasubstituted analogues. Oxidation of thioester affinity ligands to their sulfonyl analogues for the para-substituted compounds decreased AR binding affinities and similar modification increased binding affinities for corresponding meta-analogues. The least potent para-substituted sulfonyl compounds had higher AR binding affinities than the most potent meta- substituted sulfonyl compounds. Overall, the para-substituted unoxidized molecules demonstrated the highest AR binding affinity. Subsequent research using AR exchange assays and Scatchard analyses showed that the isothiocyanate affinity ligands (R)-7, (R)-9, and (R)-10 reported herein are the first specific chemoaffinity ligands for the AR.