6613-41-8

Usage

Synthesis Reference(s)

Journal of the American Chemical Society, 80, p. 6386, 1958 DOI: 10.1021/ja01556a055

Upstream product

• 6362-67-0 phenyl-oxalacetic acid-anhydride 
• 64-17-5 ethanol 
• 876477-89-3 4-benzyl-3-methyl-pentenedioic acid diethyl ester 
• 141-78-6 ethyl acetate 
• 60030-15-1 2-Hydrazono-3-phenylpropionsaeureaethylester 
• 150-30-1 Phenylalanine 
• 156-06-9 2-oxo-3-(phenyl)propionic acid 
• 541-41-3 chloroformic acid ethyl ester 
• 620-79-1 Ethyl 2-benzylacetoacetate 
• 59903-89-8 (S)-3-Phenyl-2-(1-phenyl-ethylamino)-propionic acid ethyl ester 
• 59903-76-3 (S)-3-Phenyl-2-[1-phenyl-eth-(Z)-ylideneamino]-propionic acid ethyl ester 
• 59903-82-1 (S)-2-(1-Methyl-2-phenyl-ethylamino)-3-phenyl-propionic acid ethyl ester 
• 101308-40-1 ethyl 2-bromo-3-phenylpropionate 
• 15626-54-7 2-diazo-3-phenyl-propionic acid ethyl ester 

Downstream Products

• 188531-02-4 ethyl 3-[(p-nitrobenzenesulfonyl)oxy]-2-oxo-3-phenylpropanoate 
• 100-52-7 benzaldehyde 
• 70564-52-2 ethyl (E)-2-(hydroxyimino)-3-phenylpropionate 
• 869012-72-6 ethyl (2S,3S)-3-bromo-2-hydroxy-3-phenylpropanoate 
• 869012-73-7 ethyl (4S,5R)-2,4-diphenyl-4,5-dihydrooxazole-5-carboxylate 
• 126060-73-9 ethyl (2R,3R)-3-phenyl-2,3-oxiranepropanoate 
• 153433-80-8 ethyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate 
• 72015-61-3 (Z)-2-benzyloxycarbonylaminocinnamic acid 
• 74805-45-1 (Z)-N-benzyloxycarbonyldehydrophenylalanylglycine ethyl ester 
• 107625-17-2 2-methyl-5-phenylpyrazolo[1,5-a]pyrimidin-7(4H)-one 
• 138653-54-0 ethyl 7-chloro-3-phenyl-1H-indole-2-carboxylate 
• 441801-09-8 ethyl 7-fluoro-3-phenyl-1H-indole-2-carboxylate 
• 137997-26-3 3-Chloro-2-cyano-6-methylbenzo[b]thiophene 
• 64932-46-3 α-acetoxy-cinnamic acid ethyl ester 

Relevant academic research and scientific papers

Discovery and mechanistic study of thiazole-4-acylsulfonamide derivatives as potent and orally active ChemR23 inhibitors with a long-acting effect in cynomolgus monkeys

Plasmacytoid dendritic cells (pDCs) are a subset of dendritic cells that can secrete large amounts of type I interferon. ChemR23, a G protein-coupled receptor (GPCR) expressed on the surface of pDCs, contributes to the recruitment of pDCs to inflamed tissues through chemotaxis signaling, and is therefore considered an attractive target for the treatment of autoimmune diseases. We previously reported benzoxazole-based compounds that can inhibit ChemR23 signaling through receptor internalization. Although these compounds showed ChemR23 internalization on pDCs in cynomolgus monkeys after oral administration, further improvement of the pharmacokinetics profile was needed for a clinical candidate and we therefore attempted scaffold-hopping from the benzoxazole core structure leading to novel thiazole derivatives. In this report, the design, synthesis, and biological evaluation of new thiazole-based ChemR23 inhibitors were described. Through sequential structure–activity relationship studies regarding (i) the side chain of the N-acylsulfonamide moiety, (ii) the 5-position of the thiazole ring, and (iii) the 1,2,4-oxadiazol-5-one moiety, we have succeeded in finding a potent thiazole-based ChemR23 inhibitor, 14f (IC80 = 12 nM). In addition, the oral administration of 14f at 30 mg/kg to cynomolgus monkeys demonstrated a sustained pharmacological effect of ChemR23 internalization on pDCs until 8 h after dosing, which was considered a longer effect in comparison to previously reported 2-aminobenzoxazole-based ChemR23 inhibitors. This report also shows the synthesis and evaluation of fluorescein-labeled compound 45c for a mechanistic study, and we could confirm the direct binding of our thiazole derivative to ChemR23. We believe that our research on small molecule ChemR23 inhibitors and chemical probe will contribute to the elucidation and analysis of the functions of ChemR23 as well as identifying novel therapeutics for autoimmune diseases.

Palladium-Catalyzed Asymmetric Hydroesterification of α-Aryl Acrylic Acids to Chiral Substituted Succinates

A palladium-catalyzed asymmetric hydroesterification of α-aryl acrylic acids with CO and alcohol was developed, preparing a variety of chiral α-substituted succinates in moderate yields with high ee values. The kinetic profile of the reaction progress revealed that the alkene substrate first underwent the hydroesterification followed by esterification with alcohol. The origin of the enantioselectivity was elucidated by density functional theory computation.

ANTIDIABETIC ENOLIC GLUCOSIDE OF PHENYLPYRUVIC ACID

PROBLEM TO BE SOLVED: To provide an antidiabetic enolic glucoside of phenylpyruvic acid and derivatives thereof, for use as medicaments, especially normoglycemic agents, i.e. for lowering blood glucose levels to normal levels in mammals that are obese, pre-diabetic or have diabetes, obesity and/or syndrome X. SOLUTION: Compounds of the present invention help to manage blood glucose levels, i.e. helping the body by balancing the blood glucose levels; helping to keep balanced blood glucose levels, particularly in humans with diabetes; aiding by enhancing the glucose uptake by the cells and by reducing blood glucose levels, thus improving or restoring the glucose tolerance; optimizing the glycemic response; and normalizing the glucose tolerance. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT

Switchable C-H Functionalization of N-Tosyl Acrylamides with Acryloylsilanes

A controllable Rh-catalyzed protocol to access alkylation and alkenylation-annulation of N-tosyl acrylamide with acryloyl silane is reported. In contrast to the directing group or catalyst-dependent divergent sp2 C-H alkylation/alkenylation, the intrinsic property of acryloylsilane allows the switchable reaction manifold, thereby affording either alkylation or annulation products with slight modification of the reaction conditions.

Copper/ascorbic acid dyad as a catalytic system for selective aerobic oxidation of amines

A new, environmentally benign system based on an ascorbic acid (vitamin C)/copper dyad is presented, which facilitates the oxidation of amines to carbonyl compounds. The oxidation utilizes aerobic oxygen as the ultimate electron scavenger, which accepts electrons in a cascade-like fashion via a Cu+/Cu2+ and ascorbic/dehydroascorbic acid couple. Dehydroascorbic acid, the oxidation agent, finally oxidizes amine substrates in a selective fashion after forming a Schiff base intermediate. The selectivity as well as generality of the method is demonstrated on various substrates.

Method for preparing chiral diphosphines

The invention concerns a method for preparing a compound of formula (1) wherein: A represents naphthyl or phenyl optionally substituted; and Ar1, Ar2independently represent a saturated or aromatic carbocyclic group, optionally substituted.

Studies on non-thiazolidinedione antidiabetic agents. 1. Discovery of novel oxyiminoacetic acid derivatives

A novel series of oxyiminoacetic acid derivatives were synthesized in an effort to develop a potent antidiabetic agent, which does not contain the 2,4-thiazolidinedione moiety. These compounds were evaluated for glucose and lipid lowering effects in genetically obese and diabetic KKAy mice. Several of the compounds showed strong antidiabetic activity, including functional potency at peroxisome proliferator-activated receptor (PPAR)-γ. (Z)-2-[4-[(5-Methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]benzyloxyimino]-2-(4- phenoxyphenyl)acetic acid (25) significantly reduced plasma glucose (33%, p0.01) and plasma triglycelide levels (43%, p0.01) even at a dosage of 0.001% in diet. Pharmacokinetic analyses of 25 are also reported.

3-substituted indole antiproliferative angiogenesis inhibitors

3-Substituted indole carbohydrazides having the formula are useful for inhibiting angiogenesis and cell proliferation. Also disclosed are compositions which inhibit angiogenesis and cell proliferation and methods of inhibiting angiogenesis and cancer in a mammal.

3-substituted indole angiogenesis inhibitors

3-Substituted indole carbohydrazides having the formula are useful for inhibiting angiogenesis. Also disclosed are angiogenesis-inhibiting compositions and methods of inhibiting angiogenesis in a mammal.

Asymmetric hydrogenation method of a ketonic compound and derivative

The present invention relates to a process for the asymmetric hydrogenation of a ketonic compound and derivative. The invention relates to the use of optically active metal complexes as catalysts for the asymmetric hydrogenation of a ketonic compound and derivative. The process for the asymmetric hydrogenation of a ketonic compound and derivative is characterized in that the asymmetric hydrogenation of said compound is carried out in the presence of an effective amount of a metal complex comprising as ligand an optically active diphosphine corresponding to one of the following formulae: STR1