51161-88-7

Usage

Uses

Used in Pharmaceutical Industry:
N-Methacryloyl-L-proline is used as a reactant for the preparation of affinity ligands for the androstane receptor. These ligands are crucial in the development of drug screening assays and the study of the androstane receptor's role in various physiological processes, including cholesterol metabolism and hormone regulation.

Upstream product

• 147-85-3 L-proline 
• 920-46-7 Methacryloyl chloride 
• 344-25-2 D-Prolin 
• 7732-18-5 water 

Downstream Products

• 64838-55-7 (2S)-1-[(2S)-3-acetylthio-2-methylpropanoyl]pyrrolidine-2-carboxylic acid 
• 65167-28-4 (2S)-1-((2R)-3-(acetylthio)-2-methylpropanoyl)pyrrolidine-2-carboxylic acid 
• 106089-19-4 3(S)-(bromomethyl)-3(S)-methyl-1,4-dioxo-3,4,6,7,8,8a(S)-hexahydro-1H-pyrrolo<2,1-c><1,4>oxazine 
• 927203-28-9 (3R,8αR)-3-(bromomethyl)-3-methyl-tetrahydro-3H-pyrrolo[2,1-c][1,4]oxazine-1,4-dione 
• 75105-86-1 dicyclohexylamine salt of 1-[3-(4-chloro-3-sulfamoylbenzoylthio)-2(S)-methylpropionyl]-L-proline 
• 64805-62-5 (S)-1-[3-(acetylthio)-2-methyl-1-oxopropyl]-L-proline 
• 927203-28-9 3-bromomethyl-3-methyl-tetrahydro-pyrrolo[2,1-c][1,4]oxazine-1,4-dione 

Relevant academic research and scientific papers

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.

Mild alkaline hydrolysis of hindered esters in non-aqueous solution

Sterically hindered esters of carboxylic acids, which are considered very resistant to saponification, were rapidly and efficiently saponified in a non-aqueous medium using NaOH in MeOH/CH2Cl2 (1:9) at room temperature. Furthermore, this reaction protocol was extended and successfully applied to the hydrolysis of tosylates and N-tosyl indoles.

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.

1-(2-hydroxy-2-methyl-3-phenoxypropanoyl)indoline-4-carbonitrile derivatives as potent and tissue selective androgen receptor modulators

We present a novel series of selective androgen receptor modulators (SARMs) which shows excellent biological activity and physical properties. 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)-indoline-4-carbonitriles showed potent binding to the androgen receptor (AR) and activated AR-mediated transcription in vitro. Representative compounds demonstrated diminished activity in promoting the intramolecular interaction between the AR carboxyl (C) and amino (N) termini. This N/C-termini interaction is a biomarker assay for the undesired androgenic responses in vivo. In orchidectomized rats, daily administration of a lead compound from this series showed anabolic activity by increasing levator ani muscle weight. Importantly, minimal androgenic effects (increased tissue weights) were observed in the prostate and seminal vesicles, along with minimal repression of circulating luteinizing hormone (LH) levels and no change in the lipid and triglyceride levels. This lead compound completed a two week rat toxicology study, and was well tolerated at doses up to 100 mg/kg/day, the highest dose tested, for 14 consecutive days.

Asymmetric induction in the conjugate addition of thioacetic acid to methacrylamides with chiral auxiliaries

The conjugate addition of thioacetic acid to methacrylamides with chiral C2-symmetric trans-2,5-disubstituted pyrrolidines afforded the addition products in excellent stereoselectivities (>99% de) and good yields (80-90%). The high selectivity was attributed mainly to the steric effect of the chiral auxiliaries. The cyclic nature of the chiral auxiliaries seemed also important for both the stereoselectivity and the reaction rate. Acidic hydrolysis of the adduct containing (2R,5R)-bis(methoxymethyl)pyrrolidine gave (S)-3-mercapto-2-methylpropanoic acid, a key intermediate for captopril, in 98% ee and 96% yield. The chiral auxiliary was recovered in the demethylated form of N-Boc-(2R,3R)-bis(hydroxymethyl)pyrrolidine in 90% yield.

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.

Stereoelectronic Control of the Tertiary Ketol Rearrangement: Implications for the Mechanism of the Reaction Catalysed by the Enzymes of Branched-chain Amino Acid Metabolism, Reductoisomerase and Acetolactate Decarboxylase

The alkali-catalised rearrangement of (R)--3-hydroxy-3-methylpentan-2-one has been studied.Rearrangement via transition state having an anti arrangement of C-O bonds was preferred over that with a syn arrangement by a factor of 1.8:1.The result is of interest in relation to the mechanism of action of the enzymes reductoisomerase and acetolactate decarboxylase, both of which are involved in the metabolism of the branched-chain amino acids.The structure and relative configuration of the product 23 of bromolactonisation of N-methacryloyl L-proline 22 were determined by X-ray crystallographic analysis.

Amino Acids, 15. - Diastereoselective Addition of Thiocarboxylic Acids to 1-(Methacryloyl)proline and -prolinol Derivatives

Thiocarboxylic acids 6 adds to 1-(methacryloyl)-substituted proline and prolinol derivatives stereoselectively to give the 1-proline and -prolinol derivatives 7,7' and 9.The less soluble -diastereomers are obtained in optical yields >/= 98percent by digestion of the crude products, the configuration of which was determined by acid hydrolysis of -7,7' to (R)-3-mercapto-2-methylpropionic acid .The stereoselectivity of the additions may be explained by a seven-membered ring intermediate with an intramolecular H bridge, to which the S-nucleophiles add preferentially to give the compounds with the (2'R)-configuration. - Keywords: Amino acids/ Diastereoselective addition/ 1-(Methacryloyl)proline derivatives

ASYMMETRIC BROMOLACTONIZATION REACTION: SYNTHESIS OF OPTICALLY ACTIVE 2-HYDROXY-2-METHYLALKANOIC ACIDS FROM 2-METHYLENEALKANOIC ACIDS

Optically pure 2-hydroxy-2-methylalkanoic acids of either configuration may be obtained via an asymmetric bromolactonization reaction using L-proline as a chiral auxilliary.

Method for preparing (+)R-2-methyl-hexane-1,2-diol

A method for preparing important stereospecific intermediates in the synthesis of prostaglandin analogs is disclosed. Said intermediates are (+)R-2-methyl-hexane-1,2-diol and (-)S-2-methyl-hexane-1,2-diol and are prepared via an asymmetric halolactonization reaction utilizing L-proline and D-proline, respectively as the chiral agent.