63 results about "Tetrazine" patented technology

The present disclosure generally relates to tetrazine-based targeting agents for bioorthogonal delivery of a payload to a targeted location in a subject for use in, for example, cancer, treatment of tumor growth, and immunotherapy.

The invention discloses a tetrazine probe synthon and a preparation method and application thereof.The preparation method comprises the following steps that under the inert atmosphere, diethyl cyanomethylphosphonate, 3-hydroxypropionitrile, 3-mercaptopropionic acid and hydrazine hydrate are mixed and then react at the room temperature, a sodium nitrite solution is added after the reaction is finished, then acid is continuously added till the reaction system reaches acidity, and a tetrazine probe synthon product is obtained; continuously reacting to obtain an intermediate; and dissolving the intermediate in a solvent in an inert atmosphere, adding triethylamine, slowly adding methanesulfonyl chloride, and reacting at room temperature to obtain the tetrazine probe synthon shown in the formula I. The invention further discloses a preparation method of the tetrazine probe synthon. The tetrazine probe synthon provided by the invention can perform series Heck reaction and HWE reaction, so that controllable combination of functional groups on two sides of a tetrazine coupling probe is realized under mild reaction conditions, and the functional groups on two sides are designed according to actual requirements to regulate and control photophysical properties of the probe. A brand new way is provided for developing a high-performance biological orthogonal fluorescent probe.

The application discloses application of a divinyl tetrazine in cyclization of a linear polypeptide, and a structure formula of the divinyl tetrazine is; the linear polypeptide has at least two free mercapto groups, and the vinyl groups of the divinyl tetrazine are subjected to Michael addition reaction with corresponding mercapto groups to form a ring. The application provides a new use of the divinyl tetrazine, the divinyl tetrazine can be subjected to high-efficiency Michael addition reaction with two natural cysteine mercapto groups on the linear polypeptide through the vinyl groups, so that double-mercapto peg cyclization of the linear polypeptide is realized, and the purpose of limiting the conformation of the linear polypeptide and improving the stability of the linear polypeptide is achieved. Moreover, the divinyl tetrazine can be subjected to a reverse electron demand Diels-Alder reaction with trans-cyclooctene (TCO) after the two vinyl groups are subjected to reaction with mercapto groups, so that functional polypeptides can be modularly constructed by coupling with functional molecules modified with TCO, and related applications are realized.

This invention belongs to the field of semiconductor manufacturing and circuit board electroplating technology, and particularly relates to an acidic copper sulfate electroplating solution containing a tetrazine structure, its preparation method, and its application. The electroplating solution is prepared by the following method: first, anhydrous copper sulfate is dissolved in ultrapure water, and then sulfuric acid, chloride ions, inhibitors, accelerators, and synergist 3,6-bis(pyridin-3-yl)-1,2,4,5-tetrazine are added sequentially under stirring conditions, and the mixture is stirred until homogeneous. This invention also provides a method for using the above electroplating solution in TSV blind via electroplating, including pretreatment of a TSV silicon blind via substrate with a diameter of 10 µm and a depth of 30 µm, using it as a cathode, clamping it with a platinum electrode, and placing it in the copper sulfate electroplating solution for electroplating. The electroplating solution formulation of this invention has a synergistic effect, exhibits excellent filling performance in TSV blind via electroplating, and is suitable for electroplating processes of high aspect ratio microvias.

The present disclosure relates to ureido ligands targeting PSMA comprising a moiety targeting PSMA, a linker, and a pyridazine moiety. The disclosed PSMA-targeted ureido ligands are suitable for use as radiopharmaceuticals, as imaging agents (e.g., diagnostic agents), or for the treatment of prostate cancer, or as diagnostic agents.

A calix[4]arenes of the formula (1a),wherein: Y1, Y2, Y3 and Y4 are selected from hydrogen, halogen, NO2, N3, CN, CHO, COOR′, CONR″2, NR2, triazole moiety and C1-C3-alkyl group, the C1-C3-alkyl group being optionally substituted, Z is a heterocyclic moiety which is selected from the group including of imidazole, benzimidazole, benzothiazole, benzoxazole, purine, tetrazine, oxazole, pyrazole and thiazole, the heterocyclic moiety being optionally substituted, R1 and R2 are selected from hydrogen and C1-C8-alkyl, the C1-C8-alkyl group being optionally substituted, n being an integer between 1 and 4, They exhibit high cytotoxicity against cancer cells.

The application discloses a kind of single-substituted 1,2,4,5-tetrazine compounds based on five-membered heterocyclic ring and preparation method thereof.The single-substituted 1,2,4,5-tetrazine compounds based on five-membered heterocyclic ring keep high reaction rate (10 4 ~10 5 M ‑1 s ‑1 ), improve the LUMO+1 orbital energy of single-substituted tetrazine compound to improve its stability, or improve the reaction ability of tetrazine compound under the same or similar LUMO+1 orbital energy, so that the single-substituted 1,2,4,5-tetrazine compounds based on five-membered heterocyclic ring have higher stability when the reaction rate is certain, have higher reaction rate when the stability is certain, provide a new idea for breaking the limitation of orbital energy and reaction ability with trans-cyclooctene, can promote the retro Diels-Alder reaction of 1,2,4,5-tetrazine compound and trans-cyclooctene in vivo, and is of great significance to the field of medicine.

The present application belongs to the technical field of rubbers, and particularly relates to a rubber composition and a preparation method therefor, and an OTR engineering tire using same. The rubber composition disclosed in the present application comprises (in parts by mass) 100 parts of a diene rubber, 0-1.5 parts of a tetrazine compound, 0.2-1.5 parts of a pyrazolone compound, 0-30 parts of a liquid rubber, 20-100 parts of a reinforcing filler, 0-5 parts of a silane coupling agent, 2-10 parts of a vulcanization activator, and a vulcanization accelerator, a vulcanizing agent, an antioxidant, a resin and a plasticizer. Moreover, the ratios of the tetrazine compound and the liquid rubber are not zero at the same time. The present application can significantly reduce the heat generated by the OTR engineering tire, and can also improve the damage resistance of the tire.

According to the phenothiazine functional precursor, the photosensitizer and the preparation method of the phenothiazine functional precursor, halogen or thienyl is introduced into R1 and / or R2 sites of a benzophenothiazine structure to serve as heavy atoms on the basis of structure-function relationship research of benzophenothiazine site modification, generation of strong spin-orbital coupling can be promoted, and the photosensitizer has the advantages that the photosensitizer can be used as a photosensitizer; further, intersystem crossing of the phenothiazine photosensitizer from an excited singlet state (S1) to a triplet state (T1) is promoted, so that the photosensitive effects of the phenothiazine functional precursor and the corresponding phenothiazine photosensitizer are effectively improved. Besides, after the phenothiazine photosensitizer is modified by adding a tetrazine group, controllable closing and opening of phenothiazine are realized, so that the dark toxicity of phenothiazine is effectively reduced, the targeting property and the treatment effect of the photosensitizer are improved by accessing a targeting group and a drug group into the phenothiazine photosensitizer, and the phenothiazine photosensitizer has a wide application prospect.

The invention relates to a macroporous pyrene tetraketone-triazine covalent organic framework material as well as a synthesis method and application thereof, and belongs to the technical field of organic functional materials. The material is prepared from 2, 7-aminopyrene-4, 5, 9, 10-tetraketone and 4, 4 ', 4' '-(1, 3, 5-triazine-2, 4, 6-triyl) tri (benzaldehyde) through polymerization. The material has a relatively large mesoporous structure, high crystallinity and rich redox active sites. The large-size mesoporous structure is favorable for keeping relatively high ion flux of the diaphragm, the bidirectional catalytic action of pyrene tetraketone conjugated carbonyl can improve the reaction kinetics of the high-load lithium-sulfur battery, and the soft-package lithium-sulfur battery prepared under the conditions of high-activity load and poor electrolyte shows stable cycle performance and relatively high specific capacity.

The present invention relates to fibroblast activation protein (FAP) - based ligands assembled through tetrazine ligation and their use in radiotherapy and imaging. The FAP inhibitor (FAPi) ligand compounds provided herein comprises a FAP targeting moiety, a linker, an IsoF-TCO and a radiolabeled tetrazine. The FAPi targeting compounds are possessing advantageous pharmacokinetic properties and enable quick and efficient modifications of the radiopharmaceuticals allowing a fast renal excretion and reduced liver accumulation.

The invention belongs to the technical field of organic compound preparation, and discloses a photochemical preparation method of a tetraphenylhexahydrotetrazine compound. The preparation method comprises the following steps: mixing an azobenzene compound, biborate, a carbon source and an organic solvent, wherein the carbon source comprises alkyl aldehyde or nitroalkane; and reacting under light irradiation, removing the organic solvent, and separating and purifying to obtain the compound. The tetraphenylhexahydrotetrazine compound with high yield can be prepared by taking an azobenzene compound as a raw material, taking aldehyde or nitroalkane as a carbon source, adding bis (borate), and carrying out illumination in the absence of a metal catalyst within the reaction time of less than 1 hour. Moreover, the preparation method disclosed by the invention shows wide functional group compatibility, so that various types of azobenzene compounds can be converted into tetraphenylhexahydrotetrazine compounds, and the application prospect is wide.

The present invention provides bioorthogonal tetrazine reaction entities for use in pretargeting approaches comprising imaging, therapy and diagnostics specifically pretargeting theranostics. The present invention also provides precursors of the tetrazine reaction entities and kits comprising the tetrazine reaction entity or the precursor of the tetrazine reaction entity and a dienophile with inverse electron demand Diels-Alder cycloaddition reactivity.

The invention relates to the technical field of biological medicine, particularly discloses a novel coupling method of double-target nucleic acid molecules and application thereof, and provides a strategy method for connecting two nucleic acid chains through cyclization reaction between tetrazine and alkene or alkyne. According to the present invention, a cyclization reaction is performed between a nucleic acid chain of a tetrazine group (Strand 1) and a nucleic acid chain of an alkene or alkyne group (Strand 2), a connection unit of dihydropyridazine or pyridazine is generated between the two nucleic acid chains, and four connection modes are selected: between 5'of Strand 1 and 3 'of Strand 2, between 5' of Strand 1 and 5 'of Strand 2, and between 3' of Strand 1 and 5 'of Strand 2. Furthermore, two nucleic acid chains connected with dihydropyridazine or pyridazine are respectively combined with complementary nucleic acid chains according to complementary base pairing to prepare a double-target oligonucleotide drug.

CRISPR-Cas genome editing technology has applications in biomedical research and therapeutics that has led to an increased demand for guide RNAs. Synthesis of chemically modified single-guide RNAs (sgRNAs)>100 nt remains a bottleneck. A tetrazine ligation method is disclosed herein for the preparation of sgRNAs that overcomes this synthesis challenge. For example, a tetrazine moiety on a 3′-end of crRNA and a norbornene moiety on a 5′-end of tracrRNA permits ligation between crRNA and tracrRNA to form an sgRNA under mild conditions. Tetrazine-ligated sgRNAs allow efficient genome editing as demonstrated by reporter models and endogenous loci in human cells. A structural modification of the linker moiety permits achievement of high efficiency editing.

This application relates to additives for imparting low heat generation properties to rubber components. The additive, which is used to impart low heat generation properties to rubber components, contains a tetrazine compound or a salt thereof represented by the following general formula (1). Wherein, X... 1 and X 2 "Same" or "different" refers to a hydrogen atom, alkyl, alkylthio, aralkyl, aryl, arylthio, heterocyclic, or amino group. Each of the above groups may have more than one substituent.

The invention relates to the technical field of chemical separation, in particular to an adsorbent based on a metal organic framework material as well as a preparation method and application of the adsorbent. The adsorbent is constructed by zinc ions, 3, 6-di-4-pyridyl-1, 2, 4, 5-tetrazine ligand and polycycloalkane dicarboxylic acid ligand H2L; h2L is selected from at least one of compounds with the structural formula shown in the attached drawing of the specification. The preparation method comprises the following step of: reacting metal salt and a ligand in a mixed solvent of N, N-dimethylformamide and methanol at 100 DEG C to obtain the metal complex. The adsorbent has the ethane adsorption capacity and selectivity higher than those of ethylene under mild conditions, and can be used for adsorption processes such as a fixed bed, so that ethylene penetrates preferentially, and high-purity ethylene gas is obtained in one step. The material has the advantages of being simple and convenient to synthesize, high in stability and easy to regenerate, and an energy-saving and efficient new scheme is provided for ethane / ethylene separation.

The application discloses a tetrazine cyanine compound and a preparation method and application thereof. The skeleton of the tetrazine cyanine compound is directly connected with a BFI part of cyanine, can better affect the overall fluorescence opening multiple of the tetrazine cyanine compound by adjusting an R1 group, can also realize high-resolution imaging of a lysosome, an endoplasmic reticulum and a mitochondrial membrane by selecting a suitable R1 group and cooperating with a predetermined site molecule, can realize high fluorescence opening multiple in a near-infrared region, can significantly enhance a fluorescence emission signal from an extremely low background level after reacting with BCN, and can also have excellent light stability, wherein the fluorescence intensity of a TBCy3P addition product generated in situ is basically maintained unchanged in the whole irradiation period under continuous 100-frame laser scanning excitation, and the cell morphology is normal.

The present invention addresses the problem of providing a rubber composition with which it is possible to suppress the occurrence of cracks while also improving fuel efficiency. As a means for solving said problem, this rubber composition is characterized by including: a diene rubber (A); a heterocyclic compound (B) having at least one heterocycle selected from the group consisting of a pyrimidine ring, a pyridazine ring, a pyrazine ring, a triazine ring, and a tetrazine ring; and an anti-aging agent (C). The rubber composition is also characterized in that the anti-aging agent (C) includes at least one selected from the group consisting of phenylenediamine-based anti-aging agents (C1-1) represented by a specific structural formula and aminoquinoline-based anti-aging agents (C1-2) represented by a specific structural formula.

The present invention addresses the problem of providing a rubber composition with which it is possible to suppress the occurrence of cracks while also improving fuel efficiency. As a means for solving said problem, this rubber composition is characterized by including: a diene rubber (A); a heterocyclic compound (B) having at least one heterocycle selected from the group consisting of a pyrimidine ring, a pyridazine ring, a pyrazine ring, a triazine ring, and a tetrazine ring; and an anti-aging agent (C). The rubber composition is also characterized in that the anti-aging agent (C) includes a triphenylamine-based anti-aging agent (C1) represented by a specific structural formula.

This disclosure generally relates to tetrazine-based targeting agents for bioorthogonal delivery of payloads to targeted sites in a subject, which have applications, for example, in the treatment of cancer, tumor growth, and immunotherapy.

The present invention discloses a pharmaceutical composition having activity of anti-tumor comprising a therapeutically effective amount of one or more compounds of formula I as the active ingredient, conventional pharmaceutically acceptable carriers, and one or more pharmaceutically acceptable acidic components, wherein said acidic component is selected from a group consisting of oleic acid, stearic acid, linolenic acid, fumaric acid, benzoic acid, tartaric acid, sorbic acid, lactic acid, citric acid, acetic acid and EDTA, wherein X is 0 or S; R is substituted or unsubstituted C3˜C10 straight or branched alkyl, C3˜C10 cycloalkyl, C3˜C10 straight or branched alkenyl or C3˜C10 straight or branched chain alkynyl; and if R has substituting group, said substituting group may be C1˜C6 alkyl, C1˜C6 alkoxy, C1˜C6 alkylthio group, C1˜C6 alkyl amino group, phenyl or phenyl substituted by halogen. Further, said composition may be made into all sorts of conventional dosage forms, in particular the oral dosage forms and topically administered transdermal dosage form. In addition, the invention discloses a method to use the composition for treatment of tumor.

This invention discloses an NPTTz-based anionic energetic complex, prepared by a volatilization method using 6-(4-nitro-1H-pyrazole-1-yl)-[1,2,4]triazolo[4,3-b][1,2,4,5]tetraazine and metal nitrates as raw materials. The NPTTz-based anionic energetic complex of this invention exhibits a detonation response upon laser irradiation, demonstrating good safety and detonation performance. It can be used as a laser-initiated detonator or as a component of explosives and propellants. Furthermore, the NPTTz-based anionic energetic complex of this invention exhibits good catalytic activity and can be used as an ammonium perchlorate catalyst, showing promising application prospects in the field of high-energy insensitive energetic materials.

The invention belongs to the field of medicinal chemistry, and discloses a red-light-started light cage dihydrotetrazine compound or a preparation method and application thereof. In particular to a light cage dihydrotetrazine compound containing dipyrromethene boron (BODIPY) or anthocyanin (CYANINE) or pharmaceutically acceptable salt of the light cage dihydrotetrazine compound, a preparation method of the light cage dihydrotetrazine compound, a pharmaceutical composition containing the light cage dihydrotetrazine compound and pharmaceutical application of the light cage dihydrotetrazine compound. The compound provided by the invention can generate tetrazine under red light starting, overcomes the problems of high toxicity of short-wavelength ultraviolet light and blue light to organisms and poor tissue penetrability, provides a new tool for time-space controllable precise drug delivery and biomarker research, and has wide clinical application prospects.

This invention discloses an anionic energetic complex based on AMPTTz, its preparation method, and its application. AMPTTz is 3-amino-6-(3,5-dimethylpyrazol-1-yl)-1,2,4-triazol[4,3-b]-[1,2,4,5]tetraazine. The general structural formula of the anionic energetic complex based on AMPTTz is [X m (AMPTTz) p Y t (H2O) q ] n In the formula ·zH₂O, X is a metal cation, and Y is an acid radical anion; the values ​​of m range from 1 to 2, p from 1 to 6, t from 1 to 5, q from 0 to 2, and z from 0 to 3. The AMPTTz-based anionic energetic complex prepared in this invention exhibits a detonation response upon laser irradiation, demonstrating good safety and detonation performance. It can be used as a laser-initiated explosive or as a component of explosives and propellants, showing promising application prospects in the field of high-energy insensitive energetic materials. Furthermore, the AMPTTz-based anionic energetic complex prepared in this invention can also serve as a combustion catalyst for modified double-base propellants, significantly improving the combustion rate and reducing the platform pressure index.

The present invention provides dual-functional tetrazine compounds for labeling with either metals including radiometals or with halogens including radiohalogens suitable for therapeutic or diagnostic purposes. Alternatively, the tetrazines can be used as precursors for labeling with a radiohalogen when the compound comprises a leaving group. The tetrazines are specifically engineered to facilitate efficient and stable incorporation of various radionuclides. By integrating a chelator group for radiometals and a leaving group for radiohalogens, these tetrazines offer a flexible and interchangeable structure that facilitates the development of radiopharmaceuticals. The tetrazines are for use in pretargeting therapy, diagnostics, imaging and theranostics. Use of the precursors for labeling with radiohalogen and use of the tetrazines as reagent in tetrazine ligation is moreover disclosed.

The application discloses a preparation method of a four-dimension covalent organic framework with a double interpenetrating structure, and comprises the following steps: 1, 5, 5'-(1, 2, 4, 5-tetrazine-3, 6-diyl) bisphenyl-1, 3-diamine and 1, 3, 5-tri-(p-formylphenyl) benzene are added into a high-pressure-resistant glass container containing a mixed solvent of mesitylene and dioxane, and an acetic acid solution is added; 2, nitrogen is injected into the container, and the container is sealed after degassing; 3, the sealed container is placed in an oven, and heating and heat preservation are carried out; 4, the reactants are cooled, filtered, washed, and vacuum dried, so that a double-interpenetrating four-dimension covalent organic framework with an ffc topological structure is obtained, and the structural formula of the four-dimension covalent organic framework is The yield is about 60%; the four-dimension covalent organic framework material with the double interpenetrating structure is obtained through an aldehyde-amine condensation condensation reaction; the preparation method is simple in operation, excellent in photocatalytic performance, and conducive to the recycling of the catalyst; and is suitable for urea production.

The invention provides a triazole pyridine extractant-hollow tetrazinyl COF composite material as well as a preparation method and application thereof, and relates to the technical field of material preparation. The preparation method comprises the following steps: firstly, taking hydroformylated SiO2 as a hard template, carrying out step-by-step polymerization and alkali etching to obtain a tetraazinyl covalent organic framework (COF) material of an ethylene connecting bond with a hollow structure, and then further introducing an extracting agent molecule with a specific multi-tooth coordination structure into a cavity of the tetraazinyl covalent organic framework (COF) material by utilizing a pressure difference-concentration difference method to obtain the composite material. According to the composite material, the high specific surface area and short mass transfer path of the hollow structure, the strong coordination capability of the tetrazine group and the high selective recognition function of the extraction agent are synergistically integrated, so that the composite material shows high adsorption capacity, fast adsorption kinetics, excellent selectivity and good reusability on thorium ions; the method has important application value in the field of efficient separation and recovery of actinide elements in radioactive wastewater.

The present invention relates to novel tetrazine compounds of formula I, wherein one of R1-R5 is 18F, for use in pretargeted in vivo imaging. The compounds are suitable for use in click chemistry, i.e. reactions that join a targeting molecule and a reporter molecule. The invention further relates to precursors to formula I, wherein one of R1-R5 is SnR3, B(OR)2, B(0H)2. Formula (I).

The application provides a kind of N 6 -(1,3,4-oxadiazol-2-yl)-[1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine and its synthesis method and application, the energetic group is introduced on the [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine skeleton, the N 6 -(1,3,4-oxadiazol-2-yl)-[1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine has the performance advantages of high enthalpy of formation, good stability and low sensitivity, has application potential in high safety and high energy density materials, the preparation method is simple, easy to synthesize, and the yield is high.