35081-45-9

Usage

Uses

Used in Pharmaceutical Industry:
4'-Benzyloxy-2-bromopropiophenone is used as a key intermediate in the synthesis of Bazedoxifene acetate (B129250) for the pharmaceutical industry. Bazedoxifene acetate is a selective estrogen receptor modulator (SERM) that is utilized in the treatment of moderate to severe hot flashes and osteoporosis in postmenopausal women. 4'-Benzyloxy-2-bromopropiophenone plays a vital role in the production process, enabling the creation of this important medication.

Upstream product

• 4495-66-3 4-benzyloxypropiophenone 
• 637-27-4 phenyl propionate 
• 108-95-2 phenol 
• 100-44-7 benzyl chloride 
• 100-39-0 benzyl bromide 
• 70-70-2 4-hydroxypropiophenone 

Downstream Products

• 103163-10-6 1-(4-benzyloxy-phenyl)-2-dibenzylamino-propan-1-one 
• 395-29-9 (+)-Isoxsuprin 
• 395-29-9 (-)-Isoxsuprin 
• 35133-39-2 1-(4-(benzyloxy)phenyl)-2-(4-benzylpiperidin-1-yl)propan-1-one 
• 98203-40-8 C₂₈H₂₈N₂O₄ 
• 137548-57-3 2-(4-benzyloxyphenyl)-6-methoxy-3-methylindole 
• 52446-73-8 1-(4-Benzyloxy-phenyl)-2-[2-(4-hydroxy-phenyl)-ethylamino]-propan-1-one 

Relevant academic research and scientific papers

Toxicity of the amphetamine metabolites 4-hydroxyamphetamine and 4-hydroxynorephedrine in human dopaminergic differentiated SH-SY5Y cells

Amphetamine (AMPH) is a psychostimulant used worldwide by millions of patients in the clinical treatment of attention deficit hyperactivity disorder, narcolepsy or even obesity, and is also a drug of abuse. 4-Hydroxynorephedrine (4-OHNE) and 4-hydroxyamphetamine (4-OHAMPH) are two major metabolites known to persist in the brain longer than AMPH. The contribution of AMPH metabolites for its neurotoxicity is undetermined. We evaluated the toxicity of AMPH and its metabolites 4-OHNE and 4-OHAMPH, obtained by chemical synthesis, in human dopaminergic differentiated SH-SY5Y neurons. Cells were exposed to AMPH (concentration range 0–5 mM) or 4-OHAMPH or 4-OHNE (concentration range 0–10 mM) for 24 or 48 h, and the viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) leakage assays. Results showed that for both AMPH and the metabolites a concentration-dependent toxicity was observed. The toxic concentration 50% (TC50) for AMPH and 4-OHNE following 24 h exposure was circa 3.5 mM and 8 mM, respectively. For 4-OHAMPH the TC50 was not reached in the tested concentration range. N-acetyl cysteine, cycloheximide, L-carnitine, and methylphenidate were able to reduce cell death induced by AMPH TC50. Acridine orange/ethidium bromide staining showed evident signs of late apoptotic cells and necrotic cells following 24 h exposure to AMPH 3.50 mM. The 4-OHAMPH metabolite at 8.00 mM originated few late apoptotic cells, whereas 4-OHNE at 8.00 mM resulted in late apoptotic cells and necrotic cells, in a scenario similar to AMPH. In conclusion, the AMPH metabolite 4-OHNE is more toxic than 4-OHAMPH, nonetheless both are less toxic than the parent compound in vitro. The most toxic metabolite 4-OHNE has longer permanence in the brain, rendering likely its contribution for AMPH neurotoxicity.

Synthesis, Antiproliferative Effect, and Topoisomerase II Inhibitory Activity of 3-Methyl-2-phenyl-1 H-indoles

A series of 3-methyl-2-phenyl-1H-indoles was prepared and investigated for antiproliferative activity on three human tumor cell lines, HeLa, A2780, and MSTO-211H, and some structure-activity relationships were drawn up. The GI50 values of the most potent compounds (32 and 33) were lower than 5 μM in all tested cell lines. For the most biologically relevant derivatives, the effect on human DNA topoisomerase II relaxation activity was investigated, which highlighted the good correlation between the antiproliferative effect and topoisomerase II inhibition. The most potent derivative, 32, was shown to induce the apoptosis pathway. The obtained results highlight 3-methyl-2-phenyl-1H-indole as a promising scaffold for further optimization of compounds with potent antiproliferative and antitopoisomerase II activities.

BETA-HYDROXYETHYLAMINES FOR USE IN THE TREATMENT OR PREVENTION OF NON-ALCOHOLIC FATTY LIVER DISEASES

There is herein provided a compound of formula (I) or a pharmaceutically acceptable salt thereof, for use in the treatment of a non-alcoholic fatty liver disease (NAFLD), such as non-alcoholic steatohepatitis (NASH), wherein X, R1, R2, R3 and n have meanings as provided in the description.

Heteroaryl estrogen receptor regulating agent and application thereof

The invention provides a compound as shown in a formula (I) and a heteroaryl estrogen receptor regulating agent including the same, belonging to the technical field of medicines. The heteroaryl estrogen receptor regulating agent further comprises a calcium phosphosilicate microsphere carrier, wherein the carrier includes silicon oxide, calcium oxide and phosphorus pentoxide in a weight ratio of 20: 4: 1, and the diameters of the microspheres are in a range of 300 to 1100 nm. The compound and the regulating agent provided by the invention can be used as estrogen receptor degrading agents, AKR1C3 inhibitors and bone resorption inhibitors for treating estrogen receptor related diseases or illnesses of patients and can be applied to the treatment of breast cancer, endometriosis and osteoporosis. The preparation method for the regulating agent can prolong the shelf life of the compound, increase the loading amount of a microsphere product, and enhance the stability and sustained release performance of the regulating agent; and the regulating agent provides a supersaturation amount of Ca in a biological fluid environment for binding to bone tissue nucleation sites so as to promote regeneration or repairing of bone tissue.

PROCESS FOR THE PREPARATION OF BAZEDOXIFENE

The invention relates to a process for preparation of the compound 3-methyl-5-benzyloxy-2-(4-benzyloxyphenyl)-1H-indole 5, an intermediate for the synthesis of bazedoxifene and bazedoxifene acetate.

INDOLE DERIVATIVES AS ESTROGEN RECEPTOR DEGRADERS

The present disclosure relates to compounds and a pharmaceutically acceptable salt thereof, compositions, combinations and medicaments containing the compounds, and processes for their preparation. The disclosure also relates to the use of the compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of the estrogen receptor, including degrading the estrogen receptor, the treatment of diseases and conditions mediated by the estrogen receptor.

COMPOUNDS FOR THE TREATMENT OF HYPERGLYCAEMIA

There is herein provided a compound of formula (I) or a pharmaceutically acceptable salt thereof, for use in the treatment of hyperglycaemia or a disorder characterized by hyperglycaemia, such as type 2 diabetes, wherein X, R1, R2, R3 and n have meanings as provided in the description.

Piperazinone compounds and application thereof

The invention belongs to the technical field of medicine and relates to 1-ethyl-4-[4-[5-hydroxy-2-(4-hydroxyphenyl)-3-methyl-1H-indole-1-yl]butyl]piperazine-2,3-dione as well as a medical application, a stereoisomer and pharmaceutically acceptable salt thereof. The structural formula of 1-ethyl-4-[4-[5-hydroxy-2-(4-hydroxyphenyl)-3-methyl-1H-indole-1-yl] butyl]piperazine-2,3-dione is represented in the specification; 1-ethyl-4-[4-[5-hydroxy-2-(4-hydroxyphenyl)-3-methyl-1H-indole-1-yl]butyl]piperazine-2,3-dione and pharmaceutically acceptable acid addition salt of the compound can be combined with existing drugs or can be independently used as an estrogen receptor modulator for treating or preventing various estrogen function related diseases such as bone loss, fracture, osteoporosis, hectic fever, LDL cholesterol level rise, cardiovascular disease, cognitive impairment, brain degeneration disease and anxiety, as well as depression, sexual dysfunction, hypertension, retinal degeneration and cancer caused by estrogen deficiency, especially osteoporosis.

Aq HBr–NaNO2–KI/air: a new catalytic system for α-monobromination of ketones

An efficient approach for α-bromination of aryl alkyl ketones, utilizing a system consisting of aqueous hydrobromic acid as bromine source, sodium nitrite–KI as catalyst, and air as terminal oxidant, has been developed. The method offers advantages of selective monobromination, mild reaction conditions, broad substrate scope, and good yield. The use of air as the terminal oxidant makes the reaction very attractive from both economical and environmental viewpoints.

Wavelength-dependent optoacoustic imaging probes for NMDA receptor visualisation

The cellular localisation and binding specificity of two NMDAR-targeted near-IR imaging probes has been examined by microscopy, followed by exemplification of MSOT to monitor simulated glutamate bursts in cellulo and a preliminary study in mice observing the signal in the brain.