39896-32-7

Upstream product

• 38411-41-5 (3-nitrophenyl)acetyl chloride 
• 108-59-8 malonic acid dimethyl ester 
• 105104-40-3 Okahara's reagent 
• 79048-31-0 tributyl(3-nitrophenyl)stannane 
• 103-79-7 1-phenyl-acetone 
• 98-95-3 nitrobenzene 
• 67-64-1 acetone 
• 108-22-5 Isopropenyl acetate 
• 99-09-2 3-nitro-aniline 
• 1877-73-2 3-nitro-benzeneacetic acid 
• 64-19-7 acetic acid 
• 586-36-7 3-nitrophenyldiazonium tetrafluoroborate 
• 124525-54-8 2-methyl-3-(3-nitrophenyl)propenoic acid 
• 39157-06-7 α-methyl-m-nitrocinnamic acid chloride 

Downstream Products

• 144380-86-9 1-Methyl-2-(3-nitro-phenyl)-ethylideneamine 
• 185557-10-2 5-Hydroxy-5-methyl-4-(3-nitro-phenyl)-5H-furan-2-one 
• 593960-54-4 1-bromo-1-(3-nitrophenyl)propan-2-one 
• 1185464-60-1 2-methyl-2-(3-nitrobenzyl)-1,3-dioxolane 
• 1402614-83-8 C₁₃H₁₅NO₅ 
• 1402614-15-6 N-(3-(1-(4-cyanophenyl)-3-methyl-6-oxo-1,6-dihydropyridazin-4-yl)phenyl)ethanesulfonamide 
• 1402614-89-4 C₁₁H₁₁NO₅ 
• 1402615-02-4 C₁₁H₁₁N₃O 
• 1402615-04-6 C₁₃H₁₅N₃O₃S 
• 1402614-42-9 N-(3-(1-(3,4-dichlorophenyl)-3-methyl-6-oxo-1,6-dihydropyridazin-4-yl)phenyl)ethanesulfonamide 
• 1402614-94-1 C₁₁H₁₁N₃O₃ 
• 1402614-35-0 (3-(1-(3,5-dichlorophenyl)-3-methyl-6-oxo-1,6-dihydropyridazin-4-yl)-phenyl)ethanesulfonamide 
• 185557-16-8 6-Methyl-5-(3-nitro-phenyl)-2H-pyridazin-3-one 
• 185557-22-6 6-Chloro-3-methyl-4-(3-nitro-phenyl)-pyridazine 

Relevant academic research and scientific papers

Abolishing Dopamine D2long/D3Receptor Affinity of Subtype-Selective Carbamoylguanidine-Type Histamine H2Receptor Agonists

3-(2-Amino-4-methylthiazol-5-yl)propyl-substituted carbamoylguanidines are potent, subtype-selective histamine H2receptor (H2R) agonists, but their applicability as pharmacological tools to elucidate the largely unknown H2R functions in the central nervous system (CNS) is compromised by their concomitant high affinity toward dopamine D2-like receptors (especially to the D3R). To improve the selectivity, a series of novel carbamoylguanidine-type ligands containing various heterocycles, spacers, and side residues were rationally designed, synthesized, and tested in binding and/or functional assays at H1-4and D2long/3receptors. This study revealed a couple of selective candidates (among others31and47), and the most promising ones were screened at several off-target receptors, showing good selectivities. Docking studies suggest that the amino acid residues (3.28, 3.32, E2.49, E2.51, 5.42, and 7.35) are responsible for the different affinities at the H2- and D2long/3-receptors. These results provide a solid base for the exploration of the H2R functions in the brain in further studies.

2-Arylamino-6-ethynylpurines are cysteine-targeting irreversible inhibitors of Nek2 kinase

Renewed interest in covalent inhibitors of enzymes implicated in disease states has afforded several agents targeted at protein kinases of relevance to cancers. We now report the design, synthesis and biological evaluation of 6-ethynylpurines that act as covalent inhibitors of Nek2 by capturing a cysteine residue (Cys22) close to the catalytic domain of this protein kinase. Examination of the crystal structure of the non-covalent inhibitor 3-((6-cyclohexylmethoxy-7H-purin-2-yl)amino)benzamide in complex with Nek2 indicated that replacing the alkoxy with an ethynyl group places the terminus of the alkyne close to Cys22 and in a position compatible with the stereoelectronic requirements of a Michael addition. A series of 6-ethynylpurines was prepared and a structure activity relationship (SAR) established for inhibition of Nek2. 6-Ethynyl-N-phenyl-7H-purin-2-amine [IC50 0.15 μM (Nek2)] and 4-((6-ethynyl-7H-purin-2-yl)amino)benzenesulfonamide (IC50 0.14 μM) were selected for determination of the mode of inhibition of Nek2, which was shown to be time-dependent, not reversed by addition of ATP and negated by site directed mutagenesis of Cys22 to alanine. Replacement of the ethynyl group by ethyl or cyano abrogated activity. Variation of substituents on the N-phenyl moiety for 6-ethynylpurines gave further SAR data for Nek2 inhibition. The data showed little correlation of activity with the nature of the substituent, indicating that after sufficient initial competitive binding to Nek2 subsequent covalent modification of Cys22 occurs in all cases. A typical activity profile was that for 2-(3-((6-ethynyl-9H-purin-2-yl)amino)phenyl)acetamide [IC50 0.06 μM (Nek2); GI50 (SKBR3) 2.2 μM] which exhibited >5-10-fold selectivity for Nek2 over other kinases; it also showed > 50% growth inhibition at 10 μM concentration against selected breast and leukaemia cell lines. X-ray crystallographic analysis confirmed that binding of the compound to the Nek2 ATP-binding site resulted in covalent modification of Cys22. Further studies confirmed that 2-(3-((6-ethynyl-9H-purin-2-yl)amino)phenyl)acetamide has the attributes of a drug-like compound with good aqueous solubility, no inhibition of hERG at 25 μM and a good stability profile in human liver microsomes. It is concluded that 6-ethynylpurines are promising agents for cancer treatment by virtue of their selective inhibition of Nek2. This journal is

UiO-66 microcrystals catalyzed direct arylation of enol acetates and heteroarenes with aryl diazonium salts in water

UiO-66 is a classic Metal–organic framework (MOF) that constructed by zirconium cations and terephthalate with high chemical and thermal stability. Using pristine UiO-66 nanocrystals as the catalysts, the carbon–carbon bond formation based on denitrogenat

C-H arylation reactions through aniline activation catalysed by a PANI-g-C3N4-TiO2 composite under visible light in aqueous medium

A PANI (polyaniline)-g-C3N4-TiO2 composite was prepared and found to be efficient for radical C-H arylation reactions. The arylation process involved coupling of in situ generated aryl diazonium salts from aniline with heteroarenes, enol acetates or benzoquinones under visible light in aqueous medium or pure water. A broad range of substrates survived the reaction conditions to provide the desired products in moderate to good yields. Scale-up (10 mmol) synthesis was also achieved. This semiconductor photocatalyst showed good photocatalytic performance and stability. Recycle studies showed that this composite could be readily recovered and a slight decrease in the catalytic activity was observed after ten consecutive runs.

Salicylic Acid-Catalyzed Arylation of Enol Acetates with Anilines

α-Aryl ketones are both structure moieties commonly found in bioactive compounds and versatile synthetic intermediates for the preparation of drug-like molecules. An operationally simple and scalable protocol has been developed to prepare α-aryl ketones from readily available aromatic amines and enol acetates (or silyl enol ethers). This metal-free methodology features the use of salicylic acid as a convenient catalyst to promote the formation of aryl radicals from in-situ generated aryl diazonium salts, without demanding thermal or photochemical activation. The mild reaction conditions used are compatible with anilines substituted with diverse functionalities. Structural elaboration of some prepared α-aryl ketones was accomplished to illustrate their usefulness as building blocks. (Figure presented.).

Porphyrins as Photoredox Catalysts in Csp2-H Arylations: Batch and Continuous Flow Approaches

We have investigated both batch and continuous flow photoarylations of enol-acetates to yield different α-arylated aldehyde and ketone building blocks by using diazonium salts as the aryl-radical source. Different porphyrins were used as SET photocatalysts, and photophysical as well as electrochemical studies were performed to rationalize the photoredox properties and suggest mechanistic insights. Notably, the most electron-deficient porphyrin (meso-tetra(pentafluorophenyl)porphyrin) shows the best photoactivity as an electron donor in the triplet excited state, which was rationalized by the redox potentials of excited states and the turnover of the porphyrins in the photocatalytic cycle. A two-step continuous protocol and multigram-scale reactions are also presented revealing a robust, cost-competitive, and easy methodology, highlighting the significant potential of porphyrins as SET photocatalysts.

A convenient and efficient one-pot synthesis of arylacetones from (E)-3-aryl-2-methylacrylic acids by curtius rearrangement

A convenient and efficient method was developed for the synthesis of arylacetones from (E)-3-aryl-2-methylacrylic acids through a Curtius rearrangement. The Curtius rearrangement of (E)-3-aryl-2-methylacryloyl azides and subsequent hydrolysis proceeded at mild temperatures in a two-phase medium of carbon tetrachloride and water containing a catalytic amount of tetrabutylammonium bromide to give the corresponding derivatives in 82-93% yield.

C-C Activation by Retro-Aldol Reaction of Two β-Hydroxy Carbonyl Compounds: Synergy with Pd-Catalyzed Cross-Coupling to Access Mono-α-arylated Ketones and Esters

A retro-aldol reaction of two β-hydroxy compounds in synergy with Pd-catalyzed cross-coupling of aryl halides is reported herein, which produces selectively mono-α-arylated ketones and esters in good yields. This reaction is compatible with a broad range of aryl iodides, bromides, chlorides, and triflates and can tolerate an array of functional groups on the aromatic ring. Ready scale-up of this reaction to gram level is applicable without an appreciable decrease in the reaction yield. Furthermore, concise syntheses of biologically active isocoumarin and indole derivatives have been achieved to greatly demonstrate the synthetic value of this retro-aldol reaction. Finally, the reaction mechanism has been discussed on the basis of experimental observations and DFT computational results. A regulated six-membered-ring transition structure has been located for the key retro-aldol C-C cleavage, which constitutes the rate-determining step of a full catalytic cycle. The concept of C-C activation by retro-aldol reaction may also find applications in other fundamental reactions.

Preparation method for aryl acetone compounds

The invention belongs to the field of organic synthesis, and specifically relates to a preparation method for aryl acetone compounds. A technical scheme of the invention is as follows: (1) with 2-methyl-3-arylacrylic acid as a starting material, carrying out a catalytic reaction of the starting material and thionyl chloride in an organic solvent through a catalyst so as to obtain 2-methyl-3-aryl acryloyl chloride, carrying out reduced pressure distillation so as to remove the organic solvent, then adding methanol, and carrying out a reaction so as to obtain methyl 2-methyl-3-arylacrylate; (2) adding hydrazine hydrate with a concentration of 80% into a reaction solution in the step 1, and carrying out a reaction so as to obtain a 2-methyl-3-aryl acrylyl hydrazine; and (3) subjecting a reaction solution in the step 2 to reduced pressure distillation so as to remove methanol, then adding the organic solvent and diluted hydrochloric acid and carrying out stirring, taking sodium nitrite and carrying out preparing into an aqueous solution, and dropwise adding the aqueous solution of sodium nitrite into a system under stirring so as to prepare aryl acetone. The method provided by the invention has the advantages of low production cost, mild reaction conditions, simple operation, high yield, and applicability to industrial production.

Discovery of non-LBD inhibitor for androgen receptor by structure-guide design

In this study, we synthesized the BF-3 binding small molecules, a series of pyridazinone-based compounds, as a novel class of non-LBP antiandrogens for treating prostate cancer by inhibiting androgen receptor. The new class compound was discovered to inhibitor the viability of AR-dependent human prostate LNCap cells and AR activity combining with the computational method. It showed a good physicochemical and PK property.