72224-22-7

Upstream product

• 15560-73-3 allyloxy-4 phenylacetate d' ethyle 
• 156-38-7 4-hydroxyphenylacetate 
• 106-95-6 allyl bromide 
• 851318-54-2 allyl (p-allyloxyphenyl)acetate 
• 17138-28-2 (4-hydroxy-phenyl)-acetic acid ethyl ester 

Downstream Products

• 1440545-91-4 SCH 71450 
• 275385-78-9 C₁₁H₁₁ClO₂ 
• 1440095-44-2 N-[2,4-bis(benzyloxy)phenethyl]-2-(4-allyloxyphenyl)acetamide 
• 1440095-48-6 (1R)-1,2,3,4-tetrahydro-1-[(4-allyloxyphenyl)methyl]-6,7-bis(benzyloxy)isoquinoline 
• 1440095-52-2 C₄₁H₃₉NO₅ 
• 1440095-56-6 C₃₈H₃₅NO₅ 
• 937808-83-8 {4-[2,3-bis(nitrooxy)propoxy]phenyl}acetic acid 
• 72224-25-0 (R,S)-4-(2,3-Epoxypropoxy)phenylacetic acid 
• 857556-03-7 [4-(2,3-dihydroxy-propoxy)-phenyl]-acetic acid ethyl ester 

Relevant academic research and scientific papers

A simple method for chemoselective phenol alkylation

A simple and effective method for chemoselective alkylation of phenol over carboxylic acid using a 40% aqueous solution of tetrabutylphosphonium hydroxide that affords the desired phenyl ethers in 82-99% yield is described.

Structure-Enabled Discovery of Novel Macrocyclic Inhibitors Targeting Glutaminase 1 Allosteric Binding Site

The inhibition of glutaminase 1 (GLS1) represents a potential treatment of malignant tumors. Structural analysis led to the design of a novel series of macrocyclic GLS1 allosteric inhibitors. Through extensive structure-activity relationship studies, a promising candidate molecule 13b (LL202) was identified with robust GLS1 inhibitory activity (IC50 = 6 nM) and high GLS1 binding affinity (SPR, Kd = 24 nM; ITC, Kd = 37 nM). The X-ray crystal structure of the 13b-GLS1 complex was resolved, revealing a unique binding mode and providing a novel structural scaffold for GLS1 allosteric inhibitors. Importantly, 13b clearly adjusted the cellular metabolites and induced an increase in the ROS level by blocking glutamine metabolism. Furthermore, 13b exhibited a similar in vivo antitumor activity as CB839. This study adds to the growing body of evidence that macrocyclization provides an alternative and complementary approach for the design of small-molecule inhibitors, with the potential to improve the binding affinity to the targets.

Synthesis and biological evaluation of 3-styrylchromone derivatives as selective monoamine oxidase B inhibitors

A series of 3-styrylchromone derivatives was synthesized and evaluated for monoamine oxidase (MAO) A and B inhibitory activities. Most of all derivatives inhibited MAO-B selectively, except compound 21. Compound 19, which had a methoxy group at R2 on the chromone ring and chlorine at R4 on phenyl ring, potently inhibited MAO-B, with an IC50 value of 2.2 nM. Compound 1 showed the highest MAO-B selectivity, with a selectivity index of >3700. Further analysis of these compounds indicated that compounds 1 and 19 were reversible and mixed-type MAO-B inhibitors, suggesting that their mode of action may be through tight-binding inhibition to MAO-B. Quantitative structure–activity relationship (QSAR) analyses of the 3-styrylchromone derivatives were conducted using their pIC50 values, through Molecular Operating Environment (MOE) and Dragon. There were 1796 descriptors of MAO-B inhibitory activity, which showed significant correlations (P 50 value index exhibited a determination coefficients (R2) of 0.972 and a Leave-One-Out cross-validated determination coefficients (Q2) of 0.914. These data suggest that the 3-styrylchromone derivatives assessed herein may be suitable for the design and development of novel MAO inhibitors.

Macrocyclic glutaminase GLS1 inhibitor or pharmaceutically acceptable salt thereof and preparation method and application thereof

The invention relates to the field of biological medicine, in particular to a series of macrocyclic glutaminase inhibitors, a synthesis method and medical application thereof, and particularly relatesto prevention or treatment of glutaminase related diseases. Meanwhile, the inventor performs a series of in-vitro anti-tumor activity evaluation on the synthesized compounds, and particularly, most of the compounds have good inhibitory activity on cancer cells.

Synthesis and biological evaluation of 3-styrylchromone derivatives as free radical scavengers and α-glucosidase inhibitors

A series of 3-styrylchromone derivatives (4-20) were synthesized and the structure-activity relationships for α-glucosidase inhibition and antioxidant activities were analyzed. Among the synthesized compounds, compounds 15 and 20, which contain a catechol moiety, showed both potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity (15: EC50 =17 μM; 20: EC50 =23 μM) and α-glucosidase inhibitory activity (15: IC50 =16 μM; 20: IC50 =10 μM). Our data suggest that 3-styrylchromone derivatives are novel α-glucosidase inhibitors that have the potential to counteract diet-induced hyperglycemia in diabetes.

Absolute stereochemical assignment of SCH 71450, a selective dopamine D4 receptor antagonist, through enantioselective epimer synthesis

The absolute stereochemical assignment of SCH 71450, a selective dopamine D4 receptor antagonist, has been successfully confirmed through enantioselective epimer synthesis. An allyl substituent on the p-hydroxybenzyl group was demonstrated to be an appropriate protecting group for Noyori Ru-catalyzed asymmetric transfer hydrogenation of the imine derivative. The construction of the sugar moiety involved a β-glycosylation reaction assisted by neighboring group participation. By comparison with literature data, the absolute stereochemistry at the C-1 carbon on the tetrahydroisoquinoline core has been assigned the S configuration. Copyright

PREPARATION AND SOME REACTIONS OF 4- AND 5-ARYL-4,5-DIHYDROPYRIDAZIN-3(2H)-ONES

Efficient preparations of 4- and 5-phenyl-4,5-dihydropyridazin-3(2H)-ones have been developed, the main reactions of these compounds have been studied, and the synthetic routes have been used to give analogues with substituents in the phenyl rings.In the best synthesis of the 4-phenyldihyropyridazinone (72 percent overall yield) the product was obtained from phenylacetic acid by three simple stages.This approach was applied in preparations of the 2- and 4-hydroxyphenyl compounds and, in conjunction with a recent method for amine protection, the 4-aminophenyl analogue.A four stage synthesis starting from benzaldehyde gave the 5-phenyldihydropyridazinone in 47 percent overall yield; hydroxybenzaldehydes were similarly converted into 5-(allyloxyphenyl)dihydropyridazinones.Oxidation to phenylpyridazinones occured more readily with the 4- and 5-phenyldihydropyridazinones than with the 6-phenyl isomer.The 4- and 5-dihydropyridazinones were smoothly reduced to tetrahydropyridazinones by hydrogenation over platinum but were uneffected by palladium in the presence of hydrazine or cyclohexene.

CARBAMYLPIPERAZINE COMPOUNDS

4-(3-Aryloxy-2-hydroxypropyl)piperazines bearing a carbamyl group in the 1-position are β-adrenergic blockers. A typical example is 1-carbamyl-4-{3-2-allyl-3-(2-carbethoxyaminoethyl)phenoxy!-2-hydroxypropyl} piperazine.