69308-37-8

Usage

Uses

Used in Pharmaceutical Industry:
(R)-4-AMINO-3-(4-CHLOROPHENYL)BUTANOIC ACID is used as a muscle relaxant for the treatment of spasticity, a condition characterized by involuntary muscle stiffness and contractions. Its agonist activity at GABA-B receptors helps in reducing spasticity by influencing neuronal excitability and neurotransmission.
Used in Neurological Applications:
As a specific GABA-B receptor agonist, (R)-4-AMINO-3-(4-CHLOROPHENYL)BUTANOIC ACID is utilized for its potential therapeutic effects in various neurological disorders. Its ability to modulate neuronal activity through GABA-B receptors makes it a candidate for the treatment of conditions such as multiple sclerosis, spinal cord injuries, and other diseases involving muscle spasticity and related symptoms.

Biological Activity

More active enantiomer of ( RS )-Baclofen ((RS)-4-Amino-3-(4-chlorophenyl)butanoic acid) , a selective GABA B agonist.

InChI:InChI=1/C10H12ClNO2/c11-9-3-1-7(2-4-9)8(6-12)5-10(13)14/h1-4,8H,5-6,12H2,(H,13,14)/t8-/m0/s1

Upstream product

• 185761-27-7 (R)-2-[(R)-4-(4-Chloro-phenyl)-4,5-dihydro-3H-pyrrol-2-ylamino]-2-phenyl-ethanol 
• 245662-60-6 1-[(3S)-3-(4-chlorophenyl)cyclobut-1-enyloxyl]-1,1-diethyl-1-silapropane 
• 290366-79-9 (R)-(-)-3-(4-chloro-phenyl)-4-nitro-butyric acid 
• 30626-03-0 (3E)-4-(4-chlorophenyl)-3-buten-2-one 
• 32271-56-0 (E)-4-(4-chlorophenyl)but-3-en-2-ol 
• 104-88-1 4-chlorobenzaldehyde 
• 1615-02-7 3-(4-chlorophenyl)prop-2-enoic acid 
• 19677-37-3 diethyl 2-(p-chlorophenyl)malonate 
• 122098-61-7 2-(4'-chlorophenyl)propane-1,3-diol 
• 63701-55-3 (R)-(-)-baclofen hydrochloride 
• 1134-47-0 4-amino-3-(4-chlorophenyl)butanoic acid 
• 852051-18-4 methyl (R)-(+)-3-(4-chlorophenyl)-4-nitrobutanoate 
• 625457-56-9 (R)-ethyl 4-[(tert-butoxycarbonyl)amino]-3-(4-chlorophenyl)butanoate 
• 200720-85-0 (E)-(S)-3-(4-Chloro-phenyl)-hex-4-enoic acid ethyl ester 

Downstream Products

• 847353-27-9 (3R)-4-{[(1R)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid 
• 847353-30-4 [3H]-Arbaclofen placarbil 
• 63701-55-3 (R)-(-)-baclofen hydrochloride 
• 1020270-34-1 (R)-3-(4-chlorophenyl)-4-nitrobutyraldehyde 
• 1252761-21-9 (R)-4-(3-amino-4-chlorophenyl)pyrrolidin-2-one 
• 1252761-51-5 (R)-4-(4-chloro-3-nitrophenyl)pyrrolidin-2-one 
• 1252763-01-1 (R)-4-amino-3-(4-chloro-3-(pyridin-4-ylmethoxy)phenyl)butanoic acid 

Relevant academic research and scientific papers

Chiral separation and modeling of baclofen, bupropion, and etodolac profens on amylose reversed phase chiral column

Chiral resolution of baclofen, bupropion, and etodolac profens was obtained with amylose derivatized chiral reversed stationary phase (carbamate groups). The eluent used for bupropion and etodolac was MeOH–water (20:80, v/v) and for baclofen was water–methanol (95:5, v/v). The eluent run rates, finding wavelength and temperature, were 1.0?mL/min, 220?nm and 27?±?1?°C for all the eluents. The magnitude of the retardation factors for S- and R-enantiomers of baclofen, bupropion, and etodolac were 1.37, 2.62, 2.25, 3.25, 1.8, and 3.0. The magnitudes of separation and resolution factors were 1.90, 1.44, and 1.67 and 2.77, 2.35, and 2.04. Limits of detection and quantitation were 1.0–2.0 and 5.1–10.0?μg/mL. Chiral recognition mechanisms were recognized by simulation and high-performance liquid chromatography (HPLC) experiments. It was seen that hydrogen interactions, hydrophobic interactions, and π–π exchanges were the chief interactions for chiral recognition mechanisms. The described methods may be exploited for the chiral separation of baclofen, bupropion, and etodolac profens in any unknown sample.

Highly Stable Zr(IV)-Based Metal-Organic Frameworks for Chiral Separation in Reversed-Phase Liquid Chromatography

Separation of racemic mixtures is of great importance and interest in chemistry and pharmacology. Porous materials including metal-organic frameworks (MOFs) have been widely explored as chiral stationary phases (CSPs) in chiral resolution. However, it remains a challenge to develop new CSPs for reversed-phase high-performance liquid chromatography (RP-HPLC), which is the most popular chromatographic mode and accounts for over 90% of all separations. Here we demonstrated for the first time that highly stable Zr-based MOFs can be efficient CSPs for RP-HPLC. By elaborately designing and synthesizing three tetracarboxylate ligands of enantiopure 1,1′-biphenyl-20-crown-6, we prepared three chiral porous Zr(IV)-MOFs with the framework formula [Zr6O4(OH)8(H2O)4(L)2]. They share the same flu topological structure but channels of different sizes and display excellent tolerance to water, acid, and base. Chiral crown ether moieties are periodically aligned within the framework channels, allowing for stereoselective recognition of guest molecules via supramolecular interactions. Under acidic aqueous eluent conditions, the Zr-MOF-packed HPLC columns provide high resolution, selectivity, and durability for the separation of a variety of model racemates, including unprotected and protected amino acids and N-containing drugs, which are comparable to or even superior to several commercial chiral columns for HPLC separation. DFT calculations suggest that the Zr-MOF provides a confined microenvironment for chiral crown ethers that dictates the separation selectivity.

COCRYSTALS OF (R)-BACLOFEN

The invention relates to novel cocrystals of (R)-Baclofen and processes for preparation thereof, and in particular to cocrystals of (R)-Baclofen with cinnamic acid, benzoic acid, salicylic acid and ferulic acid. It also refers to pharmaceutical compositions containing said cocrystals and to a use of said cocrystals or pharmaceutical compositions for the treatment of a disease or disorder selected from spasticity due to multiple sclerosis, spinal cord injury or cerebral palsy, and alcoholism.

Method for Resolution of Baclofen Salts

The invention relates to the field of resolution of chiral compounds existing in the form of two optical antipodes (enantiomers), such as Baclofen. More particularly, the invention relates to the production of the pure enantiomer (R)(?) Baclofen, of chemical nomenclature (R)-4-amino-3-(4-chlorophenyl)-butanoic acid, and the hydrogen maleate salt thereof. More specifically, the invention relates to the resolution of hydrogen maleate salts of racemic Baclofen by preferential crystallisation and particularly by the AS3PC method (auto-seeded and programmed polythermal preferential crystallisation).

Rhodium-catalyzed asymmetric hydrogenation of β-cyanocinnamic esters with the assistance of a single hydrogen bond in a precise position

With the assistance of hydrogen bonds, the first asymmetric hydrogenation of β-cyanocinnamic esters is developed, affording chiral β-cyano esters with excellent enantioselectivities (up to 99% ee). This novel methodology provides an efficient and concise synthetic route to chiral GABA-derivatives such as (S)-Pregabalin, (R)-Phenibut, (R)-Baclofen. Interestingly, in this system, the catalyst with a single H-bond donor performs better than that with double H-bond donors, which is a novel discovery in the metalorganocatalysis area.

Biocatalytic desymmetrization of 3-substituted glutaronitriles by nitrilases. A convenient chemoenzymatic access to optically active (S)-Pregabalin and (R)-Baclofen

Desymmetrization of prochiral 3-substituted glutaronitriles offers a new approach to access (S)-Pregabalin and (R)-Baclofen. A number of nitrilases from diverse sources were screened with 3-isobutylglutaronitriles (1a) or 3-(4′-chlorophenyl)glutaronitriles (1b) as the substrate. Some nitrilases were found to catalyze the desymmetric hydrolysis of 1a and 1b to form optically active 3-(cyanomethyl)-5-methylhexanoic acid (2a) and 3-(4′-chlorophenyl) -4-cyanobutanoic acid (2b) with high enantiomeric excesse (ee), respectively. This cannot be achieved using traditional chemical hydrolysis. Among them, AtNIT3 generated (R)-2b, whereas BjNIT6402 and HsNIT produced the opposite (S)-enantiomer with high conversions and ee values. Not only the nitrilases showed different activities and stereoselectivities toward these 3-substituted glutaronitriles, the 3-substituent of the substrates also exerted great effect on the enzyme activity and stereoselectivity. (S)-2a and (S)-2b were prepared with high yields and ee values using BjNIT6402 and HsNIT as the biocatalysts, respectively. A straightforward Curtius rearrangement of (S)-2a and (S)-2b, followed by the acidic hydrolysis, afforded (S)-Pregabalin and (R)-Baclofen. This offers a new platform methodology for the synthesis of optically active β-substituted γ-amino acids of pharmaceutical importance.

METHOD FOR PREPARING CHIRAL BACLOFEN

The present invention provides a novel method for preparing chiral Baclofen with higher yield, higher e.e. value, and lower cost via chiral Michael addition.

OPTICALLY ACTIVE 4-AMINO-3-(4-CHLOROPHENYL)BUTANOIC ACID

Provided is a new crystal A of optically active 4-amino-3-(4-chlorophenyl)butanoic acid which is far better in stability, and a process for producing the crystal and a process for producing the crystal A comprising a step of heating the following crystal B in water having a pH of 3 to 9: crystal A: a crystal of optically active 4-amino-3-(4-chlorophenyl)butanoic acid which has diffraction peaks within the range of a diffraction angle 2θ of 8.7 to 9.4°, within that of 2θ of 12.2 to 12.8°, and within that of 2θ of 24.8 to 25.4° in a powder X-ray diffraction measurement of the crystal by use of the Cu—Kα wavelength; and crystal B: a crystal of optically active 4-amino-3-(4-chlorophenyl)butanoic acid which has diffraction peaks within the range of a diffraction angle 2θ of 20.8 to 21.4°, within that of 2θ of 26.7 to 27.3°, and within that of 2θ of 29.7 to 30.3° in a powder X-ray diffraction measurement of the crystal by use of the Cu—Kα wavelength.

METHOD OF PRODUCING PURIFIED OPTICALLY ACTIVE 4-AMINO-3-(SUBSTITUTED PHENYL)BUTANOIC ACID COMPOUND

A method of producing a purified optically active 4-amino-3-(substituted phenyl)butanoic acid compound which is characterized by comprising a step of making a crude optically active 4-amino-3-(substituted phenyl)butanoic acid compound contact an organic acid in the presence of water.

COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS

The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.