177489-10-0

Upstream product

• 198627-86-0 1,1-dimethylethyl 4-(3-hydroxyphenyl)-1-piperazinecarboxylate 
• 109-01-3 1-methyl-piperazine 
• 108-43-0 3-monochlorophenol 
• 148546-99-0 3-(4-methylpiperazin-1-yl)aniline 
• 591-20-8 3-Bromophenol 
• 59817-32-2 3-(piperazin-1-yl)phenol 
• 57318-64-6 1-N-(3'-methoxyphenyl)-4-N-methyl-1-4-diaza-cyclohexane 

Downstream Products

• 1417454-10-4 C₂₄H₃₃N₃O₂ 
• 1110734-65-0 3-Ethyl-4-[3-(4-methyl-piperazin-1-yl)-phenoxy]-pyridine-2-carbonitrile 
• 1110734-55-8 1-[3-(3-Ethyl-4-iodo-pyridin-2-yloxy)-phenyl]-4-methyl-piperazine 
• 919088-08-7 4-[3-(4-methyl-piperazin-1-yl)-phenoxy]-benzaldehyde 

Relevant academic research and scientific papers

Synthesis and anticancer activity of novel water soluble benzimidazole carbamates

Metastases account for more than 90% of all cancer deaths and respond poorly to most therapies. There remains an urgent need for new therapeutic modalities for the treatment of advanced metastatic cancers. The benzimidazole methylcarbamate drugs, commonly

Method for continuously synthesizing meta-di-alkane aminophenol

The invention discloses a method for continuously synthesizing meta-di-alkane aminophenol. The technical scheme includes that continuous diazotization or continuous diazonium salt hydrolysis or continuous diazotization and diazonium salt hydrolysis is carried on raw materials such as di-alkane aminophenol, sodium nitrite and sulfuric acid, and after-treatment such as extraction is carried out to obtain the meta-di-alkane aminophenol which is a product. The method has the advantages that the raw materials can come from sufficient sources and are low in cost, processes for synthesizing the meta-di-alkane aminophenol are high in safety, products are high in yield, the method is little in waste gas, wastewater and industrial residue pollution, is green and environmental friendly and has a highindustrialization value, and the like.

Piperidine and piperazine inhibitors of fatty acid amide hydrolase targeting excitotoxic pathology

FAAH inhibitors offer safety advantages by augmenting the anandamide levels “on demand” to promote neuroprotective mechanisms without the adverse psychotropic effects usually seen with direct and chronic activation of the CB1 receptor. FAAH is an enzyme implicated in the hydrolysis of the endocannabinoid N-arachidonoylethanolamine (AEA), which is a partial agonist of the CB1 receptor. Herein, we report the discovery of a new series of highly potent and selective carbamate FAAH inhibitors and their evaluation for neuroprotection. The new inhibitors showed potent nanomolar inhibitory activity against human recombinant and purified rat FAAH, were selective (>1000-fold) against serine hydrolases MGL and ABHD6 and lacked any affinity for the cannabinoid receptors CB1 and CB2. Evaluation of FAAH inhibitors 9 and 31 using the in vitro competitive activity-based protein profiling (ABPP) assay confirmed that both inhibitors were highly selective for FAAH in the brain, since none of the other FP-reactive serine hydrolases in this tissue were inhibited by these agents. Our design strategy followed a traditional SAR approach and was supported by molecular modeling studies based on known FAAH cocrystal structures. To rationally design new molecules that are irreversibly bound to FAAH, we have constructed “precovalent” FAAH-ligand complexes to identify good binding geometries of the ligands within the binding pocket of FAAH and then calculated covalent docking poses to select compounds for synthesis. FAAH inhibitors 9 and 31 were evaluated for neuroprotection in rat hippocampal slice cultures. In the brain tissue, both inhibitors displayed protection against synaptic deterioration produced by kainic acid-induced excitotoxicity. Thus, the resultant compounds produced through rational design are providing early leads for developing therapeutics against seizure-related damage associated with a variety of disorders.

Synthetic method for m-dialkylaminophenol

The invention provides a synthetic method for m-dialkylaminophenol. The synthetic method is characterized by comprising the following steps: step 1, adding an aqueous solution of sodium nitrite into an aqueous solution of sulfuric acid containing m-dialkylaminoaniline drop by drop at a temperature of -10 to 20 DEG C, and maintaining the obtained solution at a temperature of 5 to 30 DEG C for 1 to10 h after completion of the addition so as to obtain an aqueous solution of sulfuric acid containing m-dialkylaminoaniline diazohydrosulfate; and step 2, directly heating aqueous solution of sulfuricacid containing m-dialkylaminoaniline diazohydrosulfate to 45-110 DEG C, maintaining the solution at the temperature for 1-18 h, allowing m-dialkylaminoaniline diazohydrosulfate to undergo the hydrolysis reaction of a diazonium salt, and successively carrying out cooling and post-treatment so as to obtain the product dialkylaminophenol, wherein sulfuric acid needed in the first step and the second step is totally added in one shot in a first-step reaction, and the first-step diazotization reaction and the second-step hydrolysis reaction of the diazonium salt are carried out step by step in one pot. The method of the invention has the characteristics of low raw material price, sufficient raw material sources, high safety, high product yield, less three-wastes pollution and the like, and has high industrialization value.

COMPOUNDS FOR TREATING PROLIFERATIVE DISEASES

The present disclosure provides compounds of Formula (I). The compounds described herein may be useful in treating and/or preventing proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.

NOVEL CATALYSTS

The present invention provides novel compounds and ligands that are useful in transition metal catalyzed cross-coupling reactions. For example, the compounds and ligands of the present invention are useful in palladium or gold catalyzed cross-coupling reactions.

SUBSTITUTED PYRAZOLO-QUINAZOLINE DERIVATIVES AS KINASE INHIBITORS

The present invention relates to substituted pyrazolo[4,3-/h]quinazoline compounds which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular PIM kinases. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing such these compounds or the pharmaceutical compositions containing them.

SUBSTITUTED PYRAZOLO-QUINAZOLINE DERIVATIVES AS KINASE INHIBITORS

The present invention relates to substituted pyrazolo[4,3-h]quinazoline compounds which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular PIM kinases. The p

A highly versatile catalyst system for the cross-coupling of aryl chlorides and Amines

The syntheses of 2-(di-tertbutylphosphino)-N,N-dimethylaniline (L1, 71%) and 2-(di-1-adamantylphosphino)-N,N-dimethylaniline (L2, 74%), and their application in BuchwaldHartwig amination, are reported. In combination with [Pd(allyl)Cl]2 or [Pd(cinnamyl)Cl]2, these structurally simple and air-stable P,N ligands enable the cross-coupling of aryl and heteroaryl chlorides, including those bearing as substituents enolizable ketones, ethers, esters, carboxylic acids, phenols, alcohols, olefins, amides, and halogens, to a diverse range of amine and related substrates that includes primary alkyl- and arylamines, cyclic and acyclic secondary amines, N-H imines, hydrazones, lithium amide, and ammonia. In many cases, the reactions can be performed at low catalyst loadings (0.5-0.02 mol % Pd) with excellent functional group tolerance and chemoselectivity. Examples of cross-coupling reactions involving 1,4-bromochlorobenzene and iodobenzene are also reported. Under similar conditions, inferior catalytic performance was achieved when using Pd(OAc)2, PdCl2, [PdCl2(cod)] (cod = 1,5-cyclooctadiene), [PdCl 2(MeCN)2], or [Pd2(dba)3] (dba = dibenzylideneacetone) in combination with L1 or L2, or by use of [Pd(allyl)Cl]2 or [Pd(cinnamyl)Cl]2 with variants of L1 and L2 bearing less basic or less sterically demanding substituents on phosphorus or lacking an ortto-dimethylamino fragment. Given current limitations associated with established ligand classes with regard to maintaining high activity across the diverse possible range of C-N coupling applications, L1 and L2 represent unusually versatile ligand systems for the cross-coupling of aryl chlorides and amines

HETEROCYCLIC COMPOUNDS AND METHODS OF USE

In one aspect, the present invention provides for a compound of Formula I; in which the variable X1a, X1b, X1c, X1d, Q, A, R1, B, L, E, and the subscripts m and n have the meanings as described herein. In another aspect, the present invention provides for pharmaceutical compositions comprising compounds of Formula I as well as methods for using compounds of Formula I for the treatment of diseases and conditions (e.g., cancer, thrombocythemia, etc) characterized by the expression or over-expression of Bcl-2 anti-apoptotic proteins, e.g., of anti-apoptotic Bcl-xL proteins.