25912-16-7

This invention concerns novel oxazine-based fluorophore compounds useful in invivo nerve imaging, as well as compositions comprising them and methods for their use.

Provided are far red to near-infrared nerve-sparing fluorescent compounds, compositions comprising them, and methods of their use in medical procedures.

Nerve-specific fluorophore formulations for direct or systemic administration are described. The formulations can be used in fluorescence-guided surgery (FGS) to aid in nerve preservation during surgical interventions.

Inter-alkane amidogen phenolic synthetic method, its characteristic is: 1st step, between the two alkane amidogen acyl aniline and sulfuric acid aqueous solution mixing and heating to 50 - 110 °C, thermal insulation reaction of aniline [...] sulfuric acid aqueous solution; 2nd step, continue to drip the sodium nitrite aqueous solution, sodium nitrite aqueous solution for dropping temperature of - 10 - 20 °C, drop bi yu 5 - 30 °C insulation, [...] aniline obtained diazonium salt of the sulfuric acid aqueous solution; 3rd step, [...] aniline diazonium salt of the sulfuric acid aqueous solution is directly heated to 45 - 110 °C, thermal insulation, in the hydrolysis reaction of the diazonium salt, cooling after treatment, to obtain the product between two alkane amidogen phenol; three-step required by the reaction of sulfuric acid in the 1st step reaction in the finished disposable adding; a three-step reaction in a finish step by step in the pot. The method of the invention with raw materials are cheap, abundant, synthetic high security of the process, the product yield is high, the three waste less pollution and the like, has high industrial value. (by machine translation)

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.

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.

The invention belongs to a lysosome positioning fluorescence probe, a preparation method, and application in arginine detection in a near infrared ratio. The chemical structure of the probe is as shown in the specification. The fluorescence probe disclosed by the invention is moderate in synthesis condition and relatively low in cost; the fluorescence probe has good selectivity and anti-interference performance for arginine; furthermore, the time and temperature stability are good; and thus, the fluorescence probe has practical application value in the field of biological chemistry.

Nucleotide-binding oligomerization domain-like receptors (NLRs) are intracellular sensors of pathogen-Associated molecular patterns (PAMPs) and damage-Associated molecular patterns (DAMPs). Previously, we reported nucleotide-binding oligomerization domain-containing protein 1 (NOD1) antagonists (11, 12) and a NOD2 antagonist (9) that sensitized docetaxel (DTX) or paclitaxel (PTX) treatment for breast or lung cancer. In this article, we describe for the first time a 1,4-benzodiazepine-2,5-dione (BZD) derivative (26bh) that acts as a dual NOD1/NOD2 antagonist and inhibits both nuclear factor B (NF-B) and mitogen-Activated protein kinase (MAPK) inflammatory signaling, thereby sensitizing PTX to suppress Lewis lung carcinoma (LLC) growth. After investigation of the compound's cytotoxicity, a systematic structure-Activity relationship (SAR) was completed and revealed several key factors that were necessary to maintain antagonistic ability. This study establishes the possibility for using adjuvant treatment to combat cancer by antagonizing both NOD1 and NOD2 signaling.

The invention discloses a substituted benzodiazepine ring compound and a preparation method and application thereof and further relates to a pharmaceutical composition and application of the compound. According to the substituted benzodiazepine ring compound, the effect of preventing or treating an immune inflammatory disease or tumor is achieved through activation of a selectively antagonistic or collaboratively excited NOD1/2 signal transduction pathway; the substituted benzodiazepine ring compound has a polypeptidase stability and is not degraded by polypeptidase in the organism.

An efficient and practical method for the synthesis of a variety of aminobenzopyranoxanthenes (ABPXs) with different nitrogen-containing fused rings was developed. On the basis of the mechanistic studies of the formation of the xanthene framework, the presented methodology was developed to facilitate access to previously inaccessible asymmetric ABPXs.

Novel N,N-dialkyl carboxy coumarins have been synthesized as potential anticancer agents via inhibition of monocarboxylate transporter 1 (MCT1). These coumarin carboxylic acids have been evaluated for their in vitro MCT1 inhibition, MTT cancer cell viability, bidirectional Caco-2 cell permeability, and stability in human and liver microsomes. These results indicate that one of the lead candidate compounds 4a has good absorption, metabolic stability, and a low drug efflux ratio. Systemic toxicity studies with lead compound 4a in healthy mice demonstrate that this inhibitor is well tolerated based on zero animal mortality and normal body weight gains compared to the control group. In vivo tumor growth inhibition studies in mice show that the candidate compound 4a exhibits significant single agent activity in MCT1 expressing GL261-luc2 syngraft model but doesn't show significant activity in MCT4 expressing MDA-MB-231 xenograft model, indicating the selectivity of 4a for MCT1 expressing tumors.

Abstract: A composite structure of ZnAl2O4–Bi2O3 nanopowder was prepared from the reaction of a watery solution of Zn(NO3)2, Al(NO3)3, and Bi(NO3)3 with a dilute solution of amino ethanol in water via a simple precipitation-complexation method. The as-prepared composite was used for the one-pot synthesis of 2-amino-4-aryl-7-(pyrrolidin-1-yl)-4H-chromene-3-carbonitrile, 2-amino-4-aryl-7-(piperidin-1-yl)-4H-chromene-3-carbonitrile, 2-amino-4-aryl-7-(1H-pyrrol-1-yl)-4H-chromene-3-carbonitrile, 2-amino-4-aryl-6-(2-(piperidin-1-yl)ethyl)-4H-chromene-3-carbonitrile and 2-amino-4-aryl-6-(1H-pyrrol-1-yl)-4H-chromene-3-carbonitrile derivatives. This procedure is very simple and affords excellent yields. Graphical Abstract: [Figure not available: see fulltext.]

N-(1-Oxy-pyridin-2-ylmethyl)oxalamic acid was identified as efficient ligand for CuI-catalyzed amination of aryl halides at room temperature. In our catalytic system, N-arylation of cyclic secondary amines, primary amines, amino acids, and ammonia proceeded with moderate to excellent yields and high functional group tolerance.

It is widely believed that the dehydrogenation of organic compounds is a thermodynamically unfavorable process, and thus requires stoichiometric oxidants such as dioxygen and metal oxides or sacrificial hydrogen acceptors to remove the hydrogen from the reaction mixture to drive the equilibrium towards the products. Here we report a previously unappreciated combination of common commercial Pd/C and H2 which dehydrogenates a wide range of substituted cyclohexanones and 2-cyclohexenones to their corresponding phenols with high isolated yields, with H2 as the only byproduct. The reaction requires no oxidants or hydrogen acceptors because instead of removing the generated hydrogen with oxidants or hydrogen acceptors, we demonstrated it can be used as a cocatalyst to help power the reaction. This method for phenol synthesis manifests a high atom economy, and is inherently devoid of the complications normally associated with oxidative dehydrogenations.

N-Arylpyrrolidines and N-arylpiperidines were synthesized in 20-88% yields by the reaction of aniline and aniline derivatives with 1,4-butane- and 1,5-pentanediols in the presence of Fecontaining catalysts and carbon tetrachloride. 1,4-Butane- and 1,5-pentanediols are partially chlorinated under the reaction conditions to give chlorohydrins, which subsequently undergo Nheterocyclization with anilines to give N-arylpyrrolidines and N-arylpiperidines.

Under hypoxia, cancer cells consume glucose and release lactate at a high rate. Lactate was recently documented to be recaptured by oxygenated cancer cells to fuel the TCA cycle and thereby to support tumor growth. Monocarboxylate transporters (MCT) are the main lactate carriers and therefore represent potential therapeutic targets to limit cancer progression. In this study, we have developed and implemented a stepwise in vitro screening procedure on human cancer cells to identify new potent MCT inhibitors. Various 7-substituted carboxycoumarins and quinolinone derivatives were synthesized and pharmacologically evaluated. Most active compounds were obtained using a palladium-catalyzed Buchwald-Hartwig type coupling reaction, which proved to be a quick and efficient method to obtain aminocarboxycoumarin derivatives. Inhibition of lactate flux revealed that the most active compound 19 (IC 50 11 nM) was three log orders more active than the CHC reference compound. Comparison with warfarin, a conventional anticoagulant coumarin, further showed that compound 19 did not influence the prothrombin time which, together with a good in vitro ADME profile, supports the potential of this new family of compounds to act as anticancer drugs through inhibition of lactate flux.

A novel class of ZnSalens (ZnL1-10) with lipophilic and cationic conjugates as optical probes in single and two-photon fluorescence microscopy images of living cells were prepared, which exhibited chemo- and photostability, low cytotoxicity and high subcellular selectivity.

This invention pertains generally to processes, uses, methods and materials utilising particular xanthylium compounds, including compounds of formula (I) and (II), as further defined herein. These compounds are useful as drugs, for example, in the treatment of tauopathies, such as Alzheimer's disease.

Five fluorescent labels were synthesized and used in the preparation of polystyrene fluorescent microspheres by the dispersion copolymerization and absorption method. Spectral properties of copolymerization fluorescent microspheres in tetrahydrofuran indicated these individual characteristics of labels should be maintained in the fluorescent microspheres. The differences of the fluorescent spectra between five fluorescent microspheres and their corresponding parent labels in ethanol have been investigated. These fluorescent microspheres were characterized by environmental scanning electron microscopy, laser scanning confocal microscopy and fluorescence spectrophotometry. They exhibited good dispersion and stable and high fluorescence intensity. Furthermore, copolymerization fluorescent microspheres were functionalized with amino groups. This means that a method for the preparation of copolymerization fluorescent microspheres was developed as a platform for the generation of functional fluorescent microspheres for diverse applications. The Royal Society of Chemistry 2009.

The first enantioselective organocatalytic intramolecular hydroarylations of phenol and aniline-derived enals were investigated. The proposed method provided an atom economic and straightforward approach to optically active chromans and tetrahydroquinolines in high enantioselectivities and in good yields. The study demonstrated the efficiency of organocatalysis to achieve the first asymmetric intramolecular arylation of ω aryloxy- arylamino-tethered α, and β-unsaturated aldehydes using a chiral secondary amine catalyst. Proposed transformation method resulted in the production of functionalized chromans and tetrahydroquinoline in high enantiopurity. The study also examined the scope of substrates in this organocatalytic reaction using a catalyst 4/p-TsOH.H2O in diethyl ether. The catalyst screening observed a higher yield up to 83% and comparable enantiometric excess up to 88% that can be obtained in a chiral secondary amine employed as the reaction catalyst.

3,7-Bis(dialkylamino)phenoxazinium salts were synthesized and evaluated for in vitro activities against Plasmodium falciparum, Trypanosoma cruzi, T. brucei rhodesiense, and Leishmania donovani. Notably, the compounds showed potent antiprotozoal activities, especially against P. falciparum and T. cruzi. The compounds with alkyl side chains less than three carbons in length possessed good activities with high selective indices.

The object of the present patent application are agents for the oxidative coloring of keratin fibers, particularly hair, based on a developer substance-coupler substance combination, characterized in that they contain at least one meta-aminophenol derivative of general formula (I), wherein R1 denotes hydrogen, a C1-C6 alkyl group, a C2-C4 hydroxyalkyl group, a C2-C4 dihydroxyalkyl group, a C1-C4 alkoxy group or a halogen atom; and R2 denotes hydrogen, a hydroxy group, a carboxylic group, an aminocarbonyl group or a hydroxymethyl group.

The present invention is directed to substituted 4H-chromenes and analogs thereof, represented by the general Formula I: 1wherein R1-R5, A, Y and Z are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

The present invention provides novel, water-soluble, red-emitting fluorescent rhodamine dyes and red-emitting fluorescent energy-transfer dye pairs, as well as labeled conjugates comprising the same and methods for their use. The dyes, energy-transfer dye pairs and labeled conjugates are useful in a variety of aqueous-based applications, particularly in assays involving staining of cells, protein binding, and/or analysis of nucleic acids, such as hybridization assays and nucleic acid sequencing.

A set of 4,7-dichlororhodamine compounds useful as fluorescent dyes are disclosed having the structures wherein R1-R6 are hydrogen, fluorine, chlorine, lower alkyl, lower alkene, lower alkyne, sulfonate, sulfone, amino, amido, nitrite, lower alkoxy, linking group, or, when taken together, R1 and R6 is benzo, or, when taken together, R4 and R5 is benzo; R7-R10, R12-R16 and R18 may be hydrogen, fluorine, chlorine, lower alkyl, lower alkene, lower alkyne, sulfonate, sulfone, amino, amido, nitrite, lower alkoxy, linking group; R11 and R17 may be hydrogen, lower alkyl, lower alkene, lower alkyne, phenyl, aryl, linking group; Y1-Y4 are hydrogen, lower alkyl, or cycloalkyl, or, when taken together, Y1 and R2, Y2 and R1 Y3 and R3, and/or Y4 and R4 is propano, ethano, or substituted forms thereof, and X1-X3 taken separately are hydrogen, chlorine, fluorine, lower alkyl, carboxylate, sulfonate, hydroxymethyl, and linking group, or any combinations thereof. In another aspect, the invention includes reagents labeled with the 4,7-dichlororhodamine dye compounds, including deoxynucleotides, dideoxynucleotides, and polynucleotides. In an additional aspect, the invention includes methods utilizing such dye compounds and reagents including dideoxy polynucleotide sequencing and fragment analysis methods.

The lithiation of 3-(dialkylamino)phenols (dialkylamino = 1-pyrrolidynyl, 1-piperidinyl, 4-morpholinyl, and dimethylamino) O-protected by a methyl, a methoxymethyl, or a carbamoyl group (X) has been studied.The results demonstrate that the site of lithiation depends on the relative ortho-directing capacities of both the dominant OX and the dialkylamino groups.With the moderate ortho-directing methoxy group the lithiation occurs exclusively (1b and 1c) or predominantly (1a) ortho to both substituents.The site of lithiation of the N,N-dialkyl-3-(methoxymethoxy)anilines 4a-c depends on the solvent used and on the type of dialkylamino group.With a strong ortho-directing group such as carbamoyloxy (9a,b,d) the lithiation takes place at the least hindered ortho position.In the absence of an electrophile the lithiated carbamates 9a,d and 10a,d rearrange stereospecifically to the corresponding benzamides 13a,d and 14a,d, respectively.

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