3617-01-4

Usage

Uses

Used in Pharmaceutical Industry:
3-(4-CHLOROPHENYL)-2-OXOPROPANOIC ACID is used as a key intermediate in the synthesis of Pyridopyrazinone derivatives, which are known as insulin secretion stimulators. These derivatives are particularly useful for treating diabetes, as they help regulate blood sugar levels and improve insulin sensitivity in patients.
In the preparation of these Pyridopyrazinone derivatives, 3-(4-CHLOROPHENYL)-2-OXOPROPANOIC ACID plays a crucial role in the development of new and more effective treatments for diabetes, offering a promising avenue for pharmaceutical research and drug development.

InChI:InChI=1/C9H7ClO3/c10-7-3-1-6(2-4-7)5-8(11)9(12)13/h1-4H,5H2,(H,12,13)

Upstream product

• 729-92-0 4-(4-chloro-benzyl)-2-trifluoromethyl-4H-oxazol-5-one 
• 58070-06-7 2-[Chloro-(4-chloro-phenyl)-methyl]-2-hydroxy-malonic acid 
• 15601-44-2 (Z/E)-4-(4-chlorobenzylidene)-2-phenyl-1,3-oxazol-5(4H)-one 
• 127220-32-0 5-[1-(4-Chloro-phenyl)-meth-(Z)-ylidene]-2-trichloromethyl-[1,3]dioxolan-4-one 
• 88681-63-4 2-acetamido-3-(4-chlorophenyl)acrylic acid 
• 93634-55-0 (Z)-4-(4-chlorobenzylidene)-2-methyloxazol-5(4H)-one 
• 104-88-1 4-chlorobenzaldehyde 
• 461-72-3 2,4-imidazolidinedione 
• 1431505-85-9 (E/Z)-methyl 3-(4-chlorophenyl)-2-dimethylaminoacrylate 
• 80540-56-3 methyl 3-(4-chlorophenyl)-2-hydroxyacrylate 
• 7424-00-2 DL-Phe(4Cl) 
• 141666-37-7 5-[1-(4-Chloro-phenyl)-1-trimethylsilanyl-meth-(Z)-ylidene]-2-trichloromethyl-[1,3]dioxolan-4-one 
• 93634-55-0 2-methyl-4-(4-chlorobenzylidene)-4H-oxazol-5-one 
• 14173-39-8 p-chlorophenylalanine 

Downstream Products

• 22900-99-8 3-(4-chloro-phenyl)-2-(4-oxo-2-thioxo-thiazolidin-5-ylidene)-propionic acid 
• 117530-89-9 4-Amino-6-(4-chloro-benzyl)-2H-[1,2,4]triazine-3,5-dione 
• 33401-57-9 6-(4-Chloro-benzyl)-3-mercapto-2H-[1,2,4]triazin-5-one 
• 117530-86-6 6-(4-Chloro-benzyl)-4-phenyl-2H-[1,2,4]triazine-3,5-dione 
• 128437-66-1 3-(4-chloro-phenyl)-3-methyl-2-oxo-butyric acid 
• 93986-07-3 3-(4-chlorobenzyl)quinoxalin-2(1H)-one 
• 202651-06-7 6-Benzo[1,3]dioxol-5-ylmethyl-3-mercapto-4-{[1-(4-methoxy-phenyl)-meth-(E)-ylidene]-amino}-4H-[1,2,4]triazin-5-one 
• 4251-65-4 (4-chlorophenyl)acetaldehyde 
• 1141478-91-2 (R)-3-(4-chlorophenyl)-2-hydroxypropanoic acid 
• 1567951-51-2 3-(4-chlorophenyl)-4-(4-methoxyphenyl)pyrrole-2-carboxylic acid 

Relevant academic research and scientific papers

Synthesis, biological activity, molecular docking studies of a novel series of 3-Aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives as the acetylcholinesterase inhibitors

The acetylcholinesterase inhibitors play a critical role in the drug therapy for Alzheimer’s disease. In this study, twenty-nine novel 3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were synthesized and assayed for their human acetylcholinesterase (hAChE) inhibitory activities. Inhibitory ratio values of seventeen compounds were above 55% with 4c having the highest value as 77.19%. The compounds with the halogen atoms in the aromatic ring, and N,N-diethylamino or N,N-dimethylamino groups in the side chains at C-3 positions exhibited good inhibitory activity. SAR study was carried out by means of molecular docking technique. According to molecular docking results, the common interacting site for all compounds were found to be peripheral anionic site whereas highly active compounds were interacting with the catalytic active site too. HIGHLIGHTS A novel series of 3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were synthesized and assayed for their human acetylcholinesterase (hAChE) inhibitory activities. The SAR study of the target 3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives was summarized. The active sites in the acetylcholinesterase were analyzed by molecular docking technique. Communicated by Ramaswamy H. Sarma.

Synthesis, β-catenin translocation capability and ALP activation activity of 7h-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives

Background: Osteoporosis (OP) is a common bone disease, most often diagnosed in post-menopausal women. The majority of OP treatments are focused on manipulation of the patient's hormone levels, therefore, they are associated with significant adverse effects. Objective: The study aimed to design, synthesize and evaluate the β-Catenin translocation capability and the alkaline phosphatase (ALP) activation activity of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives. Method: The styrene derivatives were synthesized as raw materials, followed by oxidation and condensation reactions, in which 6-aryl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one derivatives (1) were obtained. The 3,6-diaryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones (2) were obtained by a condensation reaction of compound 1 with substituted phenacyl chlorides in acetic acid. The target compounds 3,6-diaryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones (3a-3c) were prepared by compound 2 with substituted alkyl chloride by Williamson reaction. As to 6-benzyl-3-aryl-7H-thiazolo[3,2- b]-1,2,4-triazin-7-one derivatives as the target compounds, the benzaldehyde and acetylglycine used as raw materials, followed by Erlenmeyer-Pl?chl reaction, condensation reaction, hydrolysis reaction, condensation reaction, 6-benzyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one derivatives were obtained, and were converted to the target compounds 6-benzyl-3-(hydroxylaryl)-7Hthiazolo[ 3,2-b]-1,2,4-triazin-7-one derivatives (5a-5d) using reaction with substituted β-phenacyl chlorides. Finally, Williamson reaction were used to yield 6-benzyl-3-aryl-7H-thiazolo[3,2-b]- 1,2,4-triazin-7-ones as target compounds (6a-6e). The β-Catenin translocation capability and the ALP activation activity were tested, and the glycogen synthase kinase-3 (GSK-3) inhibition was simulated by molecular docking. Results: Fourteen 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were synthesized and characterized by mass spectra, proton NMR and infrared spectra, the β-Catenin translocation capability and the ALP activation activities of the target compounds were tested and calculated. The EC50 value of the ALP activation activity of 6-(4-chlorobenzyl)-3-{4-[(2-dimethylamino)-2- oxoethoxy]phenyl}-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one (6b) was 11.283 μM. The molecular docking results have showed that the target compounds would be GSK-3 inhibitors. Conclusion: Based on the results of the biological activity test, the target compounds have exhibited the β-Catenin translocation capability and the ALP activation activity.

Bio-inspired enantioselective full transamination using readily available cyclodextrin

The mimics of vitamin B6-dependent enzymes that catalyzed an enantioselective full transamination in the pure aqueous phase have been realized for the first time through the establishment of a new “pyridoxal 5′-phosphate (PLP) catalyzed non-covalent cyclodextrin (CD)-keto acid inclusion complexes” system, and various optically active amino acids have been obtained.

Design, synthesis, and biological evaluation of 7H-thiazolo[3,2-b]-1,2,4- triazin-7-one derivatives as dual binding site acetylcholinesterase inhibitors

A series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were designed, synthesized and evaluated as dual binding site acetylcholinesterase inhibitors. The target compounds exhibited promising inhibitory activity for AChE. The structure-activity relationships were discussed and their binding conformation and simultaneous interactions mode were further clarified by the molecular docking studies.

Enantioselective reduction of 3-aryl-2-oxo-propanoic acids: A comparison of enzymatic and transition-metal-catalyzed methods

Phenyllactic acids are important constituents of depsipeptides, which are a large class of natural products expressing a wide range of biological activities. Despite there being several methods for the enantioselective synthesis of α-hydroxy acids, almost no studies are available addressing the substrate selectivity of transition-metal and enzyme-catalyzed methods for the preparation of substituted phenyllactic or more general aryllactic acids. We report herein comparative results for Rh-DiPAMP (DiPAMP = 1,2-ethandiylbis[(o- methoxyphenyl)phenylphosphane]) and lactate dehydrogenase catalyzed enantioselective reductions of several 3-aryl-2-oxopropanoic acids. Phenyllactic acids are important constituents of depsipeptides, which are a large class of natural products expressing a wide range of biological activities. A comparative study of transition-metal and lactate dehydrogenase catalyzed enantioselective reductions of several 3-aryl-2-oxopropanoic acids as valuable sources for enantiomerically pure phenyllactic acids is described. Copyright

SUBSTITUTED BETA-PHENYL-ALPHA-HYDROXY PROPANOIC ACID, SYNTHESIS METHOD AND USE THEREOF

The present invention relates to a compound of the formula (I), wherein R1, R2 and R3 are each independently selected from H, OH, F, Cl, Br, methoxy and ethoxy; or alternatively, R1 and R2 together form -OCH2O-, R3 is selected from H, OH, methoxy, ethoxy and halogens; R4 is OH or acyloxy; R5 is cycloalkoxyl, amino and substituted amino, and when R5 is selected from amino, at least one of R1, R2 and R3 is not H. The present invention further relates to a process for synthesizing a compound of the formula (I), and use of the compound of the formula (I) in the manufacture of a medicament for the prevention or treatment of cardiovascular or cerebrovascular diseases.

Engineered dehydrogenase biocatalysts for non-natural amino acids: Efficient isolation of the d-enantiomer from racemic mixtures

With a view to their use in the kinetic resolution of racemic non-natural amino acids, five variants of the enzyme l-phenylalanine dehydrogenase, the wild-type enzyme from Bacillus sphaericus and four active-site mutants, have been tested with a range of amino acids. In each case, the rates of reaction with 0.2 mM l-amino acid and with the racemic mixture at 0.4 mM were compared, so that the starting concentration of the active substrate was kept constant. Although the d-amino acids are not substrates, they were inhibitory in all cases. The extent of inhibition, however, varied greatly from compound to compound and among the mutants. With the N145L mutant and dl 4-O-Me-Phe, the equimolar d-enantiomer gave 83.2% inhibition, and with the wild-type enzyme there was 86.7% inhibition with racemic norleucine. By contrast, with these same substrates the N145V mutant showed less than 9% and 24% inhibition respectively. The N145A mutant was selected for use with dl-4-Cl-Phe. The pH was decreased from the enzyme's optimum of 10.4 to 9.5 to minimise breakdown of the coenzyme NAD+, and the coenzyme was recycled by molecular oxygen with the assistance of a commercial diaphorase. Reaction on a 200 μmole scale in 20 ml ethanolamine HCl buffer, pH 9.5, with 25 μg N145A enzyme and 100 μg diaphorase, was monitored by chiral HPLC. The l-isomer was removed to an extent of >99% after 40 h, with the d-isomer peak undiminished. The pure d-isomer was isolated from the reaction mixture in 85% overall yield after ion-exchange chromatography.

Deracemisation of aryl substituted α-hydroxy esters using Candida parapsilosis ATCC 7330: Effect of substrate structure and mechanism

Candida parapsilosis ATCC 7330 was found to be an efficient biocatalyst for the deracemisation of aryl α-hydroxy esters (65-85% yield and 90-99% ee). A variety of aryl and aryl substituted α-hydroxy esters were synthesized to reflect steric and electronic effects on biocatalytic deracemisation. The mechanism of this biocatalytic deracemisation was found to be stereoinversion.

Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: Modification of the a segment

Analogs of HTI-286 (1), containing various aromatic rings in the A segment, were synthesized as potential inhibitors of tubulin polymerization, and the structure-activity relationships related to stereo- and regio-chemical effects of substituents on the a

Combinatorial synthesis through disulfide exchange: Discovery of potent psammaplin A type antibacterial agents active against methicillin-resistant Staphylococcus aureus (MRSA)

Psammaplin A is a symmetrical bromotyrosine-derived disulfide natural product isolated from the Psammaplysilla sponge, which exhibits in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Inspired by the structure of this marine natural product, a combinatorial scrambling strategy for the construction of heterodimeric disulfide analogues was developed and applied to the construction of a 3828-membered library starting from 88 homodimeric disulfides. These psammaplin A analogues were screened directly against various gram positive bacterial strains leading to the discovery of a series of potent antibacterial agents active against methicillin-resistant Staphylococcus aureus (MRSA). Among the most active leads derived from these studies are compounds 104, 105, 113, 115, 123, and 128. The present, catalytically-induced, disulfide exchange strategy may be extendable to other types of building blocks bearing thiol groups facilitating the construction of diverse discovery-oriented combinatorial libraries.