6921-66-0

Usage

Preparation

Preparation by Fries rearrangement of 3-chlorophenyl acetate with aluminium chloride,without solvent at 130–135° (74–75%) ], between 135° and 200° and 175–200° (85–89%) with solvent, at r.t., in nitrobenzene (88%), in tetrachloroethane (50%) or in chlorobenzene.

Upstream product

• 60207-19-4 1-(4-chloro-2-methoxyphenyl)-ethanone 
• 108-43-0 3-monochlorophenol 
• 75-36-5 acetyl chloride 
• 99-91-2 para-chloroacetophenone 
• 3731-51-9 2-(Aminomethyl)pyridine 
• 566945-71-9 4-chloro-2-hydroxy-N-methoxy-N-methylbenzamide 
• 917-54-4 methyllithium 
• 5106-98-9 4-chlorosalicylic acid 
• 13031-39-5 3-chlorophenyl acetate 
• 100960-68-7 4-chloro-2-methoxylbenzonitrile 
• 57479-70-6 2-methoxy-4-chlorobenzoic acid 
• 205320-02-1 4-chloro-N,2-dimethoxy-N-methylbenzamide 
• 95679-75-7 2-{1-[(4-Bromo-phenyl)-hydrazono]-ethyl}-5-chloro-phenol 

Downstream Products

• 126235-12-9 1-(4-Chloro-2-hydroxy-phenyl)-3-dimethylamino-propan-1-one; hydrochloride 
• 111391-39-0 (E)-3-(4-Benzyloxy-phenyl)-1-(4-chloro-2-hydroxy-phenyl)-propenone 
• 80055-86-3 7-chloro-2,2-dimethylchroman-4-one 
• 107113-87-1 1-(4-Chloro-2-hydroxy-phenyl)-3-hydroxy-3-(1-phenyl-2-thioxo-1,2-dihydro-pyridin-3-yl)-propan-1-one 
• 27581-19-7 2-ethyl-5-chlorophenol 
• 96755-02-1 (E)-1-(4-chloro-2-hydroxyphenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)prop-2-en-1-one 
• 36768-43-1 (E)-1-(4-chloro-2-hydroxyphenyl)-3-(4-chlorophenyl)prop-2-en-1-one 
• 1226-11-5 (E)-1-(4-chloro-2-hydroxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one 
• 89892-67-1 4-Chlor-3,5-dinitro-2-hydroxy-acetophenon 
• 30335-94-5 (2-acetyl-5-chlorophenoxy)acetic acid ethyl ester 
• 101860-74-6 7-chloro-4H-chromen-4-one 
• 60207-19-4 1-(4-chloro-2-methoxyphenyl)-ethanone 
• 114741-22-9 7-chloro-4-oxo-4H-chromene-2-carboxylic acid 
• 113850-94-5 ethyl 7-chloro-4-oxo-4H-chromene-2-carboxylate 

Relevant academic research and scientific papers

Discovery of novel 3-{[(5,5-dimethyl-4,5-dihydroisoxazol-3-yl)sulfonyl]methyl}benzo[d]isoxazole analogs as promising very long chain fatty acids inhibitors

Very long chain fatty acids (VLCFAs) are one of the most principal and promising targets for herbicides discovery. In order to explore and find novel VLCFAs inhibitors with higher herbicidal activity and improved crop safety, a variety of new 3-{[(5,5-dimethyl-4,5-dihydroisoxazol-3-yl)sulfonyl]methyl}benzo[d]isoxazole derivatives were reasonably designed and synthesized. The results of greenhouse experiments indicated that several compounds exhibited good herbicidal activity against Digitaria sanguinalis, Echinochloa crus-galli, and Setaria faberii at rates of 150 g ai/ha. Compounds g4 and h1 displayed promising herbicidal activity against D sanguinalis and E crus-galli at rates of 75 g ai/ha, which is better than commercial pyroxasulfone and S-metolachlor. Moreover, compound h1 displayed higher activity against E crus-galli, D sanguinalis, and S faberii than pyroxasulfone and S-metolachlor even at a rate of 37.5 and 18.75 g ai/ha. Furthermore, both of the compounds g4 and h1 were much safer to these tested crops, especially to rice, wheat and rape, at the rate of 150 g ai/ha than pyroxasulfone. Therefore, h1 may act as a new lead structure for novel herbicides discovery.

Rhoda-Electrocatalyzed Bimetallic C?H Oxygenation by Weak O-Coordination

Rhodium-electrocatalyzed arene C?H oxygenation by weakly O-coordinating amides and ketones have been established by bimetallic electrocatalysis. Likewise, diverse dihydrooxazinones were selectively accessed by the judicious choice of current, enabling twofold C?H functionalization. Detailed mechanistic studies by experiment, mass spectroscopy and cyclovoltammetric analysis provided support for an unprecedented electrooxidation-induced C?H activation by a bimetallic rhodium catalysis manifold.

Novel p-functionalized chromen-4-on-3-yl chalcones bearing astonishing boronic acid moiety as MDM2 inhibitor: Synthesis, cytotoxic evaluation and simulation studies

Background: Novel 4-[3-(6/7/8-Substituted 4-Oxo-4H-chromen-3-yl)acryloyl]phenyl-boronic acid derivatives (5a-h) as well as other 6/7/8-substituted-3-(3-oxo-3-(4-substituted-phenyl)prop-1-enyl)-4H-chromen-4-one derivatives (3a-u) have been designed as p53-MDM2 pathway inhibitors and reported to possess significant cytotoxic properties against several cancer cell lines. Objectives: The current project aims to frame the structure-anticancer activity relationship of chromen-4-on-3-yl chalcones (3a-u/5a-h). In addition, docking studies were performed on these chromeno-chalcones in order to have an insight into their interaction possibilities with MDM2 pro-tein. Methods: Twenty-nine chromen-4-on-3-yl chalcone derivatives (3a-u/5a-h) were prepared by utilizing silica supported-HClO4 (green route with magnificent yield) and tested against four cancer cell lines (HCT116, MCF-7, THP-1, NCIH322). Results: Among the series 3a-u, compound 3b exhibited the highest anticancer activity (with IC50 values ranging from 8.6 to 28.4 μM) overall against tested cancer cell lines. Interestingly, para-Boronic acid derivative (5b) showed selective inhibition against colon cancer cell line, HCT-116 with an IC50 value of 2.35 μM. Besides the emblematic hydrophobic interactions of MDM2 inhibi-tors, derivative 5b was found to exhibit extra hydrogen bonding with GLN59 and GLN72 residues of MDM2 in molecular dynamics (MD) simulation. All the compounds were virtually nontoxic against normal fibroblast cells. Conclusion: Novel compounds were obtained with good anticancer activity especially 6-Chlorochromen-4-one substituted boronic acid derivative 5b. The molecular docking study proposed good activity as a MDM-2 inhibitor suggesting hydrophobic as well as hydrogen bonding interactions with MDM2.

TRANSCRIPTION FACTOR BRN2 INHIBITORY COMPOUNDS AS THERAPEUTICS AND METHODS FOR THEIR USE

The invention provides a variety of compounds having the structure of Formula I and uses of such compounds for treatment of various indications, including cancer as well as methods of treatment involving such compounds are also provided. The uses of the compounds may specifically include: bladder cancer, cholangiocarcinoma; colorectal cancer; diffuse large B-cell lymphoma (DLBC); liver cancer; ovarian cancer; thymoma; thyroid cancer; clear cell renal cell carcinoma (CCRCC); chromophobe renal cell carcinoma (ChRCC); prostate cancer; breast cancer; uterine cancer; pancreatic cancer; cervical cancer; uveal melanoma; acute myeloid leukemia (AML); head and neck cancer; small cell lung cancer (SCLC); lung adenocarcinoma sarcoma; mesothelioma; adenoid cystic carcinoma (ACC), sarcoma; testicular germ cell cancer; uterine cancer; pheochromocytoma and paraganglioma (PCPG); melanoma; glioma; glioblastoma multiforme; T-cell Acute Lymphoblastic Leukemia; T-cell Lympohoma, medulloblastoma; and neuroblastoma.

Directed Hydroxylation of sp2 and sp3 C-H Bonds Using Stoichiometric Amounts of Cu and H2O2

The use of copper for C-H bond functionalization, compared to other metals, is relatively unexplored. Herein, we report a synthetic protocol for the regioselective hydroxylation of sp2 and sp3 C-H bonds using a directing group, stoichiometric amounts of Cu and H2O2. A wide array of aromatic ketones and aldehydes are oxidized in the carbonyl γ-position with remarkable yields. We also expanded this methodology to hydroxylate the β-position of alkylic ketones. Spectroscopic characterization, kinetics, and density functional theory calculations point toward the involvement of a mononuclear LCuII(OOH) species, which oxidizes the aromatic sp2 C-H bonds via a concerted heterolytic O-O bond cleavage with concomitant electrophilic attack on the arene system.

Gram-Positive and Gram-Negative Antibiotic Activity of Asymmetric and Monomeric Robenidine Analogues

Desymmetrisation of robenidine (1: N′,2-bis((E)-4-chlorobenzylidene)hydrazine-1-carboximidhydrazide) and the introduction of imine alkyl substituents gave good antibiotic activity. Of note was the increased potency of two analogues against vancomycin-resistant Enterococci (VRE), one of which returned a MIC of 0.5 μg mL?1. Five analogues were found to be equipotent or more potent than the lead 1. Introduction of an indole moiety resulted in the most active robenidine analogue against methicillin-resistant S. aureus (MRSA), with a MIC of 1.0 μg mL?1. Imine C=NH isosteres (C=O/C=S) were inactive. Monomeric analogues were 16–64 μg mL?1 active against MRSA and VRE. An analogue that lacks the terminal hydrazide NH moiety showed modest Gram-negative activity at 64 μg mL?1. A 4-tert-butyl analogue was shown to be active against both Gram-positive and -negative strains at 16–64 μg mL?1. In general, additional modifications with aromatic moieties was poorly tolerated, except with concomitant introduction of an imine C-alkyl group. The activity of these analogues against MRSA and VRE ranged from 8 μg mL?1 to inactive (MIC>128 μg mL?1) with the naphthyl and indole analogues. Gram-negative activity was most promising with two compounds at 16 μg mL?1 against E. coli. Against P. aeruginosa, the highest activity observed was with MIC values of 32 μg mL?1 with another two analogues. Combined, these findings support the further development of the (E)-2-benzylidenehydrazine-1-carboximidamide scaffold as a promising scaffold for the development of antibiotics against Gram-positive and Gram-negative strains.

Photocatalytic benzene and benzene derivative direct hydroxylation or amination method

The invention discloses a photocatalytic benzene and benzene derivative direct hydroxylation or amination method. The method is characterized by comprising the following steps: (1) adding a photo-sensitizer and a cobalt catalyst into a solvent to obtain a solution (A); (2) adding benzene (or benzene derivatives), water, ammonia gas, and amide derivatives (or sulfonamide derivatives) into the solution (A) to obtain a solution (B); and (3) in a N2 (or Ar) environment, radiating the solution (B) by a medium pressure mercury lamp, a high pressure mercury lamp, a xenon lamp, or an LED lamp to obtain phenols or amines and H2. For the first time, a photo-sensitizer and a cobalt catalyst are combined and applied to photocatalytic hydroxylation and amination of benzene. The conditions of the method are mild, light is taken as the driving energy, no oxidant is added, the only byproduct is H2, and the whole process is green, concise, and efficient. High selective benzene one-step hydroxylation to generate phenol or high selective phenol/benzene one-step amination to generate aniline is realized, and the method can be applied to the production of phenol and aniline.

A re-investigation of the Fries rearrangement of 3-chlorophenyl acetate and synthesis of 2-azido-1-(4-(benzyloxy)-2-chlorophenyl)ethanone from 4-bromo-3-chlorophenol

The Fries rearrangement of 3-chlorophenyl acetate provided the expected 4-chloro-2-hydroxy-acetophenone as the major product and 2,4-diacetyl resorcinol and 2-chloro-4-hydroxy-acetophenone as minor products. 4-Benzyloxy-2-chloroacetophenone was prepared by a Heck reaction and then elaborated to 4-benzyloxy-2-chlorophenacyl azide.

3-Formylchromone based topoisomerase IIα inhibitors: Discovery of potent leads

Substituted 3-formylchromones were synthesized and evaluated as inhibitors of the human DNA topoisomerase IIα (hTopo-IIα) enzyme. The results of the decatenation, relaxation and DNA intercalation assays revealed that the compounds (11b, 12a, 12b, 12d, 12e, 13a and 13b) exhibited potent inhibitory activity against the hTopo-IIα enzyme, and are nonintercalating agents. These compounds also possess significant in vitro cytotoxicity (LC50 ranges from 0.5-8.6 μM) against prostate (PC-3) cancerous cell line as seen in comparison to the standard drug etoposide. To further probe the plausible mode of action of 3-formylchromone derivatives, molecular docking studies have also been carried out, which showed that the compounds under investigation fitted well in the ATP binding pocket of hTopo-IIα enzyme with good docking scores and form nonbonding interactions with the crucial residues of the catalytic site. The Royal Society of Chemistry.

Chromenones as potent bradykinin B1 antagonists

A series of fused 6,6-bicyclic chromenones was investigated for activity against the bradykinin B1 receptor. SAR studies based on a pharmacophore model revealed compounds with high affinity for both human and rabbit B1. These compounds demonstrated favorable pharmacokinetic properties and 5-chlorochromenone 15 was efficacious in a carrageenan-induced mechanical hyperalgesia model for chronic pain.