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Usage

Uses

Used in Pharmaceutical Industry:
Raloxifene is used as a therapeutic agent for the treatment and prevention of osteoporosis in postmenopausal women. It helps in reducing the risk of vertebral fractures and supports bone health by modulating the effects of estrogen on bone tissue.
Additionally, raloxifene is used as an oncological agent for reducing the risk of invasive breast cancer in postmenopausal women with osteoporosis or at high risk for breast cancer. It achieves this by selectively modulating estrogen receptor activity, thereby inhibiting the growth and progression of cancer cells.

Upstream product

• 104-88-1 4-chlorobenzaldehyde 
• 111873-50-8 dibutyl(cyanomethyl)telluronium chloride 
• 75-05-8 acetonitrile 
• 590-17-0 cyanomethyl bromide 
• 6378-66-1 2-chloro-1-(4-chlorophenyl)ethanol 
• 143-33-9 sodium cyanide 
• 18293-53-3 2-trimethylsilylacetonitrile 
• 4640-66-8 p-chlorobenzoylacetonitrile 
• 773837-37-9 sodium cyanide 
• 90712-54-2 5-(4-chlorophenyl)-4,5-dihydroisoxazole 
• 1073-67-2 4-vinylbenzyl chloride 
• 7677-24-9 trimethylsilyl cyanide 
• 2788-86-5 4-Chlorostyrene oxide 
• 1446698-46-9 (dimethylsilyl)acetonitrile 

Downstream Products

• 324574-51-8 (S)-3-(4'-chlorophenyl)-3-hydroxypropanenitrile 
• 25209-46-5 3-(4-chlorophenyl)-3-hydroxypropanoic acid 
• 99839-00-6 3-(4-chlorophenyl)-3-hydroxypropanamide 
• 1207280-82-7 ethyl 3-(4-chlorophenyl)-3-hydroxypropanimidoate hydrochloride 

Relevant academic research and scientific papers

Biocatalytic asymmetric ring-opening of dihydroisoxazoles: a cyanide-free route to complementary enantiomers of β-hydroxy nitriles from olefins

By combination of the cyanide-free synthesis of chiral nitriles and the Kemp elimination reaction catalyzed by aldoxime dehydratases, we herein report a new application of aldoxime dehydratase in the asymmetric ring-opening of 5-sub-4,5-dihydroisoxazoles

NEW TRPA1 ANTAGONISTS

The present invention relates to compounds of Formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by TRPA1 channel inhibition or antagonism.

Optimization of a Novel Quinazolinone-Based Series of Transient Receptor Potential A1 (TRPA1) Antagonists Demonstrating Potent in Vivo Activity

There has been significant interest in developing a transient receptor potential A1 (TRPA1) antagonist for the treatment of pain due to a wealth of data implicating its role in pain pathways. Despite this, identification of a potent small molecule tool possessing pharmacokinetic properties allowing for robust in vivo target coverage has been challenging. Here we describe the optimization of a potent, selective series of quinazolinone-based TRPA1 antagonists. High-throughput screening identified 4, which possessed promising potency and selectivity. A strategy focused on optimizing potency while increasing polarity in order to improve intrinisic clearance culminated with the discovery of purinone 27 (AM-0902), which is a potent, selective antagonist of TRPA1 with pharmacokinetic properties allowing for >30-fold coverage of the rat TRPA1 IC50 in vivo. Compound 27 demonstrated dose-dependent inhibition of AITC-induced flinching in rats, validating its utility as a tool for interrogating the role of TRPA1 in in vivo pain models.

Substrate evaluation of rhodococcus erythropolis SET1, a nitrile hydrolysing bacterium, demonstrating dual activity strongly dependent on nitrile sub-structure

Assessment of Rhodococcus erythropolis SET1, a novel nitrile hydrolysing bacterial isolate, has been undertaken with 34 nitriles, 33 chiral and 1 prochiral. These substrates consist primarily of β-hydroxy nitriles with varying alkyl and aryl groups at the β position and containing in several compounds different substituents α to the nitrile. In the case of β-hydroxy nitriles without substitution at the α position, acids were the major products obtained, along with recovered nitrile after biotransformation, as a result of suspected nitrilase activity of the isolate. Unexpectedly, amides were found to be the major hydrolysis product when the β-hydroxy nitriles possessed a vinyl group at this position. To probe this behaviour further, additional related substrates were evaluated containing electron-withdrawing groups at the α position, and amide was also observed upon biotransformation in the presence of SET1. Therefore this novel isolate has also demonstrated NHase activity with nitriles that appears to be substrate-dependent.

Formation of carbanions from carboxylate ions bearing electron-withdrawing groups via photoinduced decarboxylation: Addition of generated carbanions to benzaldehyde

The photoinduced decarboxylation of carboxylate ions bearing electron-withdrawing groups using biphenyl and 1,4-dicyanonaphthalene leads to the efficient generation of carbanions under mild conditions. The efficiency of the carbanion generation is strongl

A magnetic nanoparticle catalyzed eco-friendly synthesis of cyanohydrins in a deep eutectic solvent

Magnetic Fe3O4 nanoparticles in deep eutectic solvents (DESs) have been regard as excellent catalysts for highly efficient cyanosilylation of various aldehydes and epoxides using trimethylsilyl cyanide TMSCN in high yields with excellent selectivity. Fe3O4 nanoparticles were synthesized and applied as a catalyst for the preparation of a wide variety of cyanohydrins (α-hydroxy nitriles and β-hydroxy nitriles) in readily available urea-choline chloride deep eutectic solvent DES as the most promising environmentally benign and cost-effective green solvent. Magnetic DES operates at very mild reaction conditions and can be easily recycled without significant loss of its catalytic activity.

Zinc-mediated addition of bromoacetonitrile to carbonyl compounds under solvent-free conditions

Zinc mediated addition reaction of bromoacetonitrile with aryl aldehydes and ketones produces β-hydroxynitriles under solvent-free conditions. The valuable feature of the methodology are solvent-free and catalyst-free conditions and short reaction times (5 min).

Multi-enzymatic biosynthesis of chiral β-hydroxy nitriles through co-expression of oxidoreductase and halohydrin dehalogenase

To establish a system for the efficient one bacterial multi-enzymatic biosynthesis of both (R)- and (S)-β-hydroxy nitriles, we co-expressed alcohol dehydrogenases with opposite stereoselectivities, cofactor regeneration enzymes, and a halohydrin dehalogenase in Escherichia coli. By researching cofactor recycling and various co-expression strategies and by selecting and engineering the halohydrin dehalogenase, we engineered two E. coli strains, which were subsequently used in a cascade of reactions to produce chiral β-hydroxy nitriles with high enantiomeric excess directly from prochiral α-halo ketones. Three valuable pharmaceutical intermediates were prepared by means of this catalytic system, and substrate conversion reached about >99%. More importantly, the system is of low cost because there is no need for expensive cofactors or for expression and purification of the component enzymes. Copyright

Nucleophilic addition of α-(dimethylsilyl)nitriles to aldehydes and ketones

α-Alkylated (dimethylsilyl)acetonitriles (Me2HSiCR 3R4CN) react spontaneously with aldehydes in DMSO to give β-hydroxynitriles in good to high yields. The addition to ketones is effectively promoted by using MgCl2/su

N-Heterocyclic carbene-catalyzed cyanomethylation of aldehydes with TMSAN

N-Heterocyclic carbenes (NHCs) have been served as efficient catalysts for cyanomethylation of carbonyl compounds. In the presence of 5 mol % NHC, various aldehydes and 2,2,2-trifluoroacetophenone reacted with trimethylsilylacetonitrile (TMSAN) to give β-hydroxynitriles in moderate to high yields.