52094-97-0

Usage

InChI:InChI=1/C10H11ClO3/c1-2-13-10(12)7-14-9-6-4-3-5-8(9)11/h3-6H,2,7H2,1H3

Upstream product

• 614-61-9 (2-chlorophenoxy)acetic acid 
• 64-17-5 ethanol 
• 95-57-8 2-monochlorophenol 
• 105-39-5 chloroacetic acid ethyl ester 
• 105-36-2 ethyl bromoacetate 

Downstream Products

• 13359-08-5 2-(2-chlorophenoxy)acetohydroxamic acid 
• 116401-10-6 2,4-bis-(2-chloro-phenoxy)-acetoacetic acid ethyl ester 
• 36304-40-2 (2-chlorophenoxy)acetic acid hydrazide 
• 131866-18-7 N,N'-bis-[(2-chloro-phenoxy)-acetyl]-hydrazine 
• 4547-67-5 ethyl (4-chlorosulfonyl-2-chloro-phenoxy)-acetate 
• 1169490-48-5 2-(2-chlorophenoxy)-3-oxobutanedioic acid diethyl ester 
• 1415405-34-3 C₁₉H₂₀ClNO₅ 
• 1415405-35-4 C₁₈H₁₈ClNO₅ 
• 1415405-36-5 C₂₀H₂₂ClNO₅ 
• 1225506-03-5 2-(2, 4-dichlorophenoxy)-N-(4-hydroxyphenyl) acetamide 
• 1134193-40-0 3,4-dihydro-4-(4-methylphenyl)-3-oxo-2H-1,4-benzoxazine 
• 1373245-74-9 3,4-dihydro-4-(3,5-dimethylphenyl)-3-oxo-2H-1,4-benzoxazine 
• 1134193-46-6 3,4-dihydro-4-(4-ethoxycarbonylphenyl)-3-oxo-2H-1,4-benzoxazine 
• 1134193-47-7 3,4-dihydro-3-oxo-4-(4-trifluoromethylphenyl)-2H-1,4-benzoxazine 

Relevant academic research and scientific papers

Discovery, synthesis and biological characterization of a series of: N -(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1 H -pyrazol-5-yl)acetamide ethers as novel GIRK1/2 potassium channel activators

The present study describes the discovery and characterization of a series of N-(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1H-pyrazol-5-yl)acetamide ethers as G protein-gated inwardly-rectifying potassium (GIRK) channel activators. From our previous lead optimization efforts, we have identified a new ether-based scaffold and paired this with a novel sulfone-based head group to identify a potent and selective GIRK1/2 activator. In addition, we evaluated the compounds in tier 1 DMPK assays and have identified compounds that display nanomolar potency as GIRK1/2 activators with improved metabolic stability over the prototypical urea-based compounds. This journal is

Expedient discovery for novel antifungal leads: 1,3,4-Oxadiazole derivatives bearing a quinazolin-4(3H)-one fragment

Developing novel fungicide candidates are intensively promoted by the rapid emergences of resistant fungi that outbreak on agricultural production. Aiming to discovery novel antifungal leads, a series of 1,3,4-oxadiazole derivatives bearing a quinazolin-4(3H)-one fragment were constructed for evaluating their inhibition effects against phytopathogenic fungi in vitro and in vivo. Systematically structural optimizations generated the bioactive molecule I32 that was identified as a promising inhibitor against Rhizoctonia solani with the in vivo preventative effect of 58.63% at 200 μg/mL. The observations that were captured by scanning electron microscopy and transmission electron microscopy demonstrated that the bioactive molecule I32 could induce the sprawling growth of hyphae, the local shrinkage and rupture on hyphal surfaces, the extreme swelling of vacuoles, the striking distortions on cell walls, and the reduction of mitochondria numbers. The above results provided an indispensable complement for the discovery of antifungal lead bearing a quinazolin-4(3H)-one and 1,3,4-oxadiazole fragment.

Design, synthesis and molecular modelling of phenoxyacetohydrazide derivatives as Staphylococcus aureus MurD inhibitors

In the present work we synthesized a new series of phenoxyacetohydrazide functional compounds 4a-k and characterized by spectral data. Synthesized compounds were screened in vitro for their antibacterial activity. Compounds 4a, 4j and 4k exhibited inhibitory activity against S. aureus NCIM 5022 with MIC value of 64?μg/ml These compounds also exhibited activity against methicillin resistant S. aureus ATCC 43300 with MIC of 128?μg/ml. Among all the tested compounds 4c and 4j showed highest activity, respectively against B. subtilis NCIM 2545 and K. pneumoniae NCIM 2706. Only one compound i.e. 4d showed activity against another Gram-negative bacteria P. aeruginosa NCIM 2036 with MIC value of 64?μg/ml. Among three tested compounds, 4k exhibited highest inhibitory activity against S. aureus MurD enzyme with IC50 value of 35.80?μM. Further binding interactions of 4a-k with the modelled S. aureus MurD catalytic pocket residues is investigated with the extra-precision molecular docking and binding free energy calculation by MM-GBSA approach. The van der Waals energy term was observed to be the driving force for binding. Further, 50?ns molecular dynamics simulations were performed to validate the stabilities of 4j- and 4k-modelled S. aureus MurD. Graphic abstract: [Figure not available: see fulltext.]

Design and synthesis of α-phenoxy-N-sulfonylphenyl acetamides as Trypanosoma brucei Leucyl-tRNA synthetase inhibitors

Human African trypanosomiasis (HAT), caused by the parasitic protozoa Trypanosoma brucei, is one of the fatal diseases in tropical areas and current medicines are insufficient. Thus, development of new drugs for HAT is urgently needed. Leucyl-tRNA synthetase (LeuRS), a recently clinically validated antimicrobial target, is an attractive target for development of antitrypanosomal drugs. In this work, we report a series of α-phenoxy-N-sulfonylphenyl acetamides as T. brucei LeuRS inhibitors. The most potent compound 28g showed an IC50 of 0.70 μM which was 250-fold more potent than the starting hit compound 1. The structure-activity relationship was also discussed. These acetamides provided a new scaffold and lead compounds for the further development of clinically useful antitrypanosomal agents.

Synthesis and computer-aided SAR studies for derivatives of phenoxyalkyl-1,3,5-triazine as the new potent ligands for serotonin receptors 5-HT6

This research has provided the most active 5-HT6R agents among 1,3,5-triazine derivatives investigated to date and has also identified the world's first selenium-containing 5-HT6R ligands. The studies are focused on design, synthesis, biological evaluation and docking-supported SAR analysis for novel 5-HT6R agents as derivatives of lead structure 4-(4-methylpiperazin-1-yl)-6-(phenoxymethyl)-1,3,5-triazin-2-amine (7). The lead modifications included an introduction of: (i) various small substituents at benzene ring, (ii) a branched ether linker or (iii) the ether oxygen replacement with other chalcogen (S, Se) or sulfonyl moiety. Hence, a series of new compounds (7–24) was synthesized and examined on their affinities for 5-HT6R and selectivity, in respect to the 5-HT1AR, 5-HT2AR, 5-HT7R and dopamine D2 receptor, in the radioligand binding assays. For representative most active compounds functional bioassays and toxicity profile in vitro and antidepressant-like activity in vivo were examined. The 2-isopropyl-5-methylphenyl derivative (10) was found as the most active triazine 5-HT6R antagonist (Ki = 11 nM). SAR analysis indicated, that an exchange of oxygen to selenium (7 vs. 22), and especially, to sulfur (7 vs. 19) was beneficial to increase both affinity and antagonistic action for 5-HT6R. Surprisingly, an introduction of SO2 caused a drastic decrease of the 5-HT6R affinity, which was explained at a molecular level based on docking studies. All in vivo tested compounds (10, 18 and 21) did not show any risk of toxicity in the safety studies in vitro.

The synthesis and evaluation of phenoxyacylhydroxamic acids as potential agents for Helicobacter pylori infections

Two series of ω-phenoxy contained acylhydroxamic acids as novel urease inhibitors were designed and synthesized. Biological activity evaluations revealed that ω-phenoxypropinoylhydroxamic acids were more active than phenoxyacetohydroxamic acids. Out of these compounds, 3-(3,4-dichlorophenoxy)propionylhydroxamic acid c24 showed significant potency against urease in both cell free extract (IC50 = 0.061 ± 0.003 μM) and intact cell (IC50 = 0.89 ± 0.05 μM), being over 450- and 120-fold more potent than the clinically prescribed urease inhibitor AHA, repectively. Non-linear fitting of experimental data (V-[S]) suggested a mixed-type inhibition mechanism and a dual site binding mode of these compounds.

Synthesis and Herbicidal Activity of Some Novel Pyrazole Derivatives

Some novel pyrazole derivatives were designed and synthesized through multi-step reactions from substituted phenol as starting material. Their structures were confirmed by 1H NMR, FTIR, MS and elemental analysis. All these compounds were evaluated their herbicidal activity. The preliminary bioassay results indicated that some of title compounds displayed moderate herbicidal activity at 200 μg/mL. Among them, compounds 4-chloro-N'-(2-(2,5-dimethyl-phenoxy) acetyl)-3-ethyl-1-methyl-1H-pyrazole-5-carbohydrazide, 4-chloro-N'-(2-(2,4-dichlorophenoxy)acetyl)- 3-ethyl-1-methyl-1H-pyrazole-5-carbohydrazide, 4-chloro-3-ethyl-1-methyl-N'-(2-(m-tolyloxy) acetyl)-1H-pyrazole-5-carbohydrazide and 4-chloro-3-ethyl-1-methyl-N'-(2-(3-nitrophenoxy)acetyl)- 1H-pyrazole-5-car-bohydrazide possessed 95%, 100%, 95% and 95% inhibition against Brassica campestris respectively. In the further bioassay, the compound 6l exhibited excellent herbicidal activity either monocotyledon or dicotyledon plant at 150 g/ha.

Design, synthesis, molecular docking and 3D-QSAR studies of potent inhibitors of enoyl-acyl carrier protein reductase as potential antimycobacterial agents

In order to develop a lead antimycobacterium tuberculosis compound, a series of 52, novel pyrrole hydrazine derivatives have been synthesized and screened which target the essential enoyl-ACP reductase. The binding mode of the compounds at the active site of enoyl-ACP reductase was explored using surflex-docking method. The binding model suggests one or two hydrogen bonding interactions between pyrrole hydrazones and InhA enzyme. Highly active compound 5r (MIC 0.2 μg/mL) showed hydrogen bonding interactions with Tyr158 and NAD+ in the same manner as those of ligands PT70 and triclosan. The CoMFA and CoMSIA models generated with database alignment were the best in terms of overall statistics. The predictive ability of the CoMFA and CoMSIA models was determined using a test set of 13 compounds, which gave predictive correlation coefficients (rpred2) of 0.896 and 0.930, respectively.

PYRAZOLO[3,4-D]PYRIMIDIN-4(5H)-ONE DERIVATIVES AS PDE9 INHIBITORS

A compound of the general formula (I) wherein R1 is selected from the group consisting of phenyl unsubstituted or substituted with 1 to 3 substituents selected from F, Cl, Br, I, CN, -O-C1-C3-alkyl, fluorinated -O-C1-C3-alkyl, -(CH2)mOH and 5-membered heterocyclic group with 1 or 2 heteroatoms selected from N, O and S; and 6- or 10-membered heteroaryl with 1 to 3 heteroatoms selected from O, N and S; R2 and R3 independently of each other represent H atom or straight or branched C1-C3 alkyl; R4 is selected from the group consisting of 4- to 6- membered cycloalkyl, wherein one of carbon atoms can be replaced by O atom, and which is unsubstituted or substituted with one or two halogen atoms,and straight or branched C1-C4 alkyl; Q represents a bond or C1-C3-alkylene, which can be optionally substituted by one to three C1-C3-alkyls; X is selected from the group consisting of O, NR5, and S(O)p; R5 represents H atom or C1-C3alkyl; m is 1, 2 or 3; p is 0, 1 or 2; and salts thereof, for use as a medicament, in particular for treating cognitive function disorders and neurodegenerative diseases.