2976-75-2

Usage

Uses

Used in Pharmaceutical Industry:
1-Naphthoxyacetic Acid is used as an internal standard for the quantitative determination of sulphonamides in meat by capillary electrophoresis with solid-phase extraction method. This application ensures accurate and reliable measurements in the analysis of sulphonamides, which are commonly used antibiotics in the livestock industry.
Used in Agricultural Industry:
1-Naphthoxyacetic Acid is used as a specific inhibitor of auxin-influx for studying the role of auxins in plant growth and development. By inhibiting auxin-influx, researchers can gain insights into the mechanisms of plant hormone regulation and potentially develop new strategies for crop management and improvement.

InChI:InChI=1/C12H10O3/c13-12(14)8-15-11-7-3-5-9-4-1-2-6-10(9)11/h1-7H,8H2,(H,13,14)/p-1

Upstream product

• 3019-88-3 sodium naphtholate 
• 105-36-2 ethyl bromoacetate 
• 90-15-3 α-naphthol 
• 79-11-8 chloroacetic acid 
• 41643-81-6 ethyl (1-naphthalenyloxy)acetate 
• 3926-62-3 sodium monochloroacetic acid 
• 107-59-5 tert-Butyl chloroacetate 
• 79-08-3 bromoacetic acid 
• 79-14-1 glycolic Acid 
• 90-14-2 1-Iodonaphthalene 
• 118688-52-1 (naphthalen-1-yloxy)acetic acid methyl ester 

Downstream Products

• 41643-81-6 ethyl (1-naphthalenyloxy)acetate 
• 2007-12-7 2-(1-naphthyloxy)acetyl chloride 
• 835-08-5 cloquintocet 
• 82746-69-8 (4-bromo-[1]naphthyloxy)-acetic acid 
• 5466-48-8 (2,4-dichloro-[1]naphthyloxy)-acetic acid 
• 63906-42-3 [1]naphthyloxy-acetic acid-(2-dimethylamino-ethyl ester); hydrochloride 
• 141171-77-9 (S)-N-tert-butyl-3-[(2S,3S)-3-[(S)-2-(1-naphthoxyacetyl)aminosuccinamyl]amino-2-hydroxy-4-phenylbutanoyl]pyrrolidine-2-carboxamide 
• 111922-86-2 (Naphthalen-1-yloxy)-acetic acid 2-oxo-2-phenyl-ethyl ester 
• 86648-76-2 (6S,7S)-2,2,4-Trimethyl-7-(naphthalen-1-yloxy)-6-phenyl-5-oxa-1-aza-bicyclo[4.2.0]octan-8-one 
• 21912-00-5 1-(1-Naphthyloxy)-3-isopropylamino-butanol-(2) 
• 141804-42-4 (R)-N-tert-butyl-3-[(2S,3S)-3-[(S)-2-(1-naphthoxyacetyl)aminosuccinamyl]amino-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide 
• 178986-94-2 (S)-3-Methyl-2-[2-(naphthalen-1-yloxy)-acetylamino]-butyric acid (1S,2S)-2-benzyloxycarbonylamino-1-((R)-4-tert-butylcarbamoyl-thiazolidine-3-carbonyl)-3-phenyl-propyl ester 
• 178986-93-1 (R)-3-Methylsulfanyl-2-[2-(naphthalen-1-yloxy)-acetylamino]-propionic acid (1S,2S)-2-benzyloxycarbonylamino-1-((R)-4-tert-butylcarbamoyl-thiazolidine-3-carbonyl)-3-phenyl-propyl ester 

Relevant academic research and scientific papers

Synthesis and optimization of peptidomimetics as HIV entry inhibitors against the receptor protein CD4 using STD NMR and ligand docking

We recently described the design and synthesis of a novel CD4 binding peptidomimetic as a potential HIV entry inhibitor with a KD value of ～35 M and a high proteolytic stability [A. T. Neffe and B. Meyer, Angew. Chem., Int. Ed., 2004, 43, 2937-2940]. Based on saturation transfer difference (STD) NMR analyses and docking studies of peptidomimetics we now report the rational design, synthesis, and binding properties of 11 compounds with improved binding affinity. Surface plasmon resonance (SPR) resulted in a KD = 10 M for the best peptidomimetic XI, whose binding affinity is confirmed by STD NMR (KD = 9 M). The STD NMR determined binding epitope of the ligand indicates a very similar binding mode as that of the lead structure. The binding studies provide structure activity relationships and demonstrate the utility of this approach. The Royal Society of Chemistry 2006.

Optimization of NAMPT activators to achieve in vivo neuroprotective efficacy

NAMPT is the rate-limiting enzyme in the NAD salvage pathway, which makes it an attractive target for the treatment of many diseases associated with NAD exhaustion such as neurodegenerative diseases. Herein, we present the systematic optimization of NAT, an initial hit of NAMPT activator discovered by us through high-throughput screening, based on the co-crystal structure of the NAMPT-NAT complex. Over 80 NAT derivatives have been designed and synthesized, among which compound 72 showed notably improved potency as NAMPT activator and effectively protected cultured cells from FK866-mediated toxicity. Moreover, compound 72 exhibited strong neuroprotective efficacy in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN) without any overt toxicity, which renders it a promising candidate for the development of novel neuroprotective agents.

SELECTIVE NON-CYCLIC NUCLEOTIDE ACTIVATORS FOR THE CAMP SENSOR EPAC1

The invention relates generally to novel EPAC1 activators, such as Formula (I) and (II) and the preparation thereof as well as the use of EPAC1 activators disclosed herein as to selectively activate EPAC1 in cells.

(Trifluoromethylselenyl)methylchalcogenyl as Emerging Fluorinated Groups: Synthesis under Photoredox Catalysis and Determination of the Lipophilicity

The synthesis of molecules bearing (trifluoromethylselenyl)methylchalcogenyl groups is described via an efficient two-step strategy based on a metal-free photoredox catalyzed decarboxylative trifluoromethylselenolation with good yields up to 88 %, which raised to 98 % in flow chemistry conditions. The flow methods allowed also to scale up the reaction. The mechanism of this key reaction was studied. The physicochemical characterization of these emerging groups was performed by determining their Hansch–Leo lipophilicity parameters with high values up to 2.24. This reaction was also extended to perfluoroalkylselenolation with yields up to 95 %. Finally, this method was successfully applied to the functionalization of relevant bioactive molecules such as tocopherol or estrone derivatives.

Synthesis and Biochemical Evaluation of Noncyclic Nucleotide Exchange Proteins Directly Activated by cAMP 1 (EPAC1) Regulators

Exchange proteins directly activated by cAMP (EPAC) play a central role in various biological functions, and activation of the EPAC1 protein has shown potential benefits for the treatment of various human diseases. Herein, we report the synthesis and biochemical evaluation of a series of noncyclic nucleotide EPAC1 activators. Several potent EPAC1 binders were identified including 25g, 25q, 25n, 25u, 25e, and 25f, which promote EPAC1 guanine nucleotide exchange factor activity in vitro. These agonists can also activate EPAC1 protein in cells, where they exhibit excellent selectivity toward EPAC over protein kinase A and G protein-coupled receptors. Moreover, 25e, 25f, 25n, and 25u exhibited improved selectivity toward activation of EPAC1 over EPAC2 in cells. Of these, 25u was found to robustly inhibit IL-6-activated signal transducer and activator of transcription 3 (STAT3) and subsequent induction of the pro-inflammatory vascular cell adhesion molecule 1 (VCAM1) cell-adhesion protein. These novel EPAC1 activators may therefore act as useful pharmacological tools for elucidation of EPAC function and promising drug leads for the treatment of relevant human diseases.

Synthesis and Biological Evaluation of Substituted Indole and Its Analogs as Influenza A Virus Inhibitors

Influenza A virus (IAV), a highly pathogenic virus to human beings, is most susceptible to mutation and thus causes rapid, severe global pandemics resulting in millions of fatalities worldwide. Since resistance to the existing anti-influenza drugs is developing, innovative inhibitors with a different mode of action are urgently needed. The lead compound 6092B-E5 has proven to be an effective antiviral reagent in our previous work. Using the principles of substitution and bioisosterism of the indole ring, six series of novel anti-IAV target products were designed, synthesized and evaluated for their antiviral effect in this work. Compounds D1, D3, D9, G1, G3, G12 and G23 were identified as promising anti-IAV candidates with excellent anti-IAV efficacy (IC50 values of 3.06–5.77 μm) and low cytotoxicity (CC50 values up to and beyond 100 μm). This work represents a successful application of the substitution and bioisosteric replacement strategy for the discovery of novel antiviral molecules that can be used for further structural optimization.

Ketoreductase catalyzed stereoselective bioreduction of α-nitro ketones

We report here the stereoselective bioreduction of α-nitro ketones catalyzed by ketoreductases (KREDs) with publicly known sequences. YGL039w and RasADH/SyADH were able to reduce 23 class I substrates (1-aryl-2-nitro-1-ethanone (1)) and ten class II substrates (1-aryloxy-3-nitro-2-propanone (4)) to furnish both enantiomers of the corresponding β-nitro alcohols, with good-to-excellent conversions (up to >99%) and enantioselectivities (up to >99% ee) being achieved in most cases. To the best of our knowledge, KRED-mediated reduction of class II α-nitro ketones (1-aryloxy-3-nitro-2-propanone (4)) is unprecedented. Select β-nitro alcohols, including the synthetic intermediates of bioactive molecules (R)-tembamide, (S)-tembamide, (S)-moprolol, (S)-toliprolol and (S)-propanolol, were stereoselectively synthesized in preparative scale with 42% to 90% isolated yields, showcasing the practical potential of our developed system in organic synthesis. Finally, the advantage of using KREDs with known sequence was demonstrated by whole-cell catalysis, in which β-nitro alcohol (R)-2k, the key synthetic intermediate of hypoglycemic natural product (R)-tembamide, was produced in a space-time yield of 178 g L?1 d?1 as well as 95% ee by employing the whole cells of a recombinant E. coli strain coexpressing RasADH and glucose dehydrogenase as the biocatalyst.

Microwave (MW), ultrasound (US) and combined synergic MW-US strategies for rapid functionalization of pharmaceutical use phenols

Increasingly stringent regulations aimed at protection of the natural environment have stimulated the search for new synthetic methodologies in organic and medicinal chemistry having no or minimum harmful effect. An interesting approach is the use of alternative activation factors, microwaves (MW) or ultrasounds (US) and also their cross-combination, which has been tested in the fast and efficient creation of new structures. At present, an easy and green hybrid strategy (“Lego” chemistry) is generally recommended for the design of new substances from different chemistry building blocks. Often, selected biologically active components with specific chemical reactivities are integrated by a suitably designed homo- or heterodifunctional linker that modifies the functionality of the starting structure, allowing easy covalent linkage to another molecule. In this study, a fast introduction of heterodifunctional halogenoacidic linker to selected mono-, di- and triphenolic active substances, allowing their functionalization, was investigated. Nucleophilic substitution reaction was chosen to produce final ethers with the reactive carboxylic group from phenols. The functionalization was performed using various green factors initiating and supporting the chemical reactions (MW, US, MW-US). The benefits of the three green supporting methods and different conditions of reactions were analyzed and compared with the results of the reaction performed by conventional methods.

Process for synthesizing naphthoxyacetic acid

The invention discloses a process for synthesizing naphthoxyacetic acid. The process comprises the following steps: reacting naphthol and an aqueous solution of alkali for dehydrating; dripping the dehydrated materials into methyl chloroacetate, and carrying out a reflux reaction so as to obtain methyl naphthyl acetate; carrying out a hydrolysis reaction under a condition that a catalyst is added into the methyl naphthyl acetate so as to obtain naphthoxyacetic acid, wherein the dehydration process comprises the sub-steps: performing reflux dehydrating, and adding a dehydrating agent for dehydrating; the pressure of the hydrothermal hydrolysis reaction is 0.2-0.8MPa; the temperature of the hydrolysis reaction is 120-200 DEG C; the pressure of the hydrolysis reaction is maintained by discharging gases in the reaction system in the process of maintaining the pressure of the hydrolysis reaction; the mass ratio of the methyl naphthyl acetate to the catalyst to the water is 1:(0.1-1):(10-20). According to the process disclosed by the invention, the methyl naphthyl acetate serving as an intermediate is used for preparing the naphthoxyacetic acid, and the highest yield of the prepared naphthoxyacetic acid can reach 95%.

Thio/oxo-naphthalimide compound and application thereof

The invention provides a thio/oxo-naphthalimide compound and application thereof. The compound has a structure shown as a general formula I. The compounds are capable of realizing competitive binding and antagonism of Bcl-2 and Mcl-1 proteins in vitro and in cells so as to induce cell apoptosis, and refer to a type of apoptosis inducers and antitumor compounds with extremely high activities. In addition, the derivative designed based on the compound can serve as a bifunctional molecule and is capable of recognizing, separating, enriching and realizing fluorescence detection of Bcl-2 family proteins; or the derivative can serve as a PROTAC bifunctional complex for selectively degrading the Bcl-2 and Mcl-1 proteins in the cells, so that the level of the Bcl-2 family proteins in living cells is regulated. The structural formula is as shown in the specification.