21 results about "Nitrogen mustard" patented technology

The application discloses a 4-(1H-benzo[d]imidazol-2-yl)-N,N-bis(2-chloroethyl) aniline derivative and a preparation method and application thereof, and belongs to the technical field of biological medicines. A structural formula is shown in the following formula I: wherein the R substituent is selected from any one of hydrogen, halogen, a carboxyl group, a cyano group, a nitro group and an alkoxy group. The application takes 4-position substituted o-phenylenediamine and 4-[bis(beta-chloroethyl)amino]benzaldehyde as raw materials, and obtains a target molecule through a condensation reaction. At present, similar nitrogen mustard or benzimidazole drug synthesis needs multiple steps of reaction, and separation and purification is complicated. The application has only one step of synthesis, a simple separation method and low requirement on equipment. In vitro anti-tumor experiments show that the target compounds synthesized by the application all have obvious anti-tumor effects, exhibit strong pharmacological activities in inhibiting tumor cell proliferation, and have wide research and development value in the field of anti-tumor drugs.

This invention provides a chlorambucil NO donor prodrug having the structure shown in Formula (I) or a pharmaceutically acceptable salt thereof: Formula (I). It involves reacting chlorambucil with a dihaloalkane to obtain a halochlorambucil intermediate; reacting the halochlorambucil intermediate with silver nitrate to obtain the chlorambucil NO donor prodrug. This invention applies the chlorambucil NO donor prodrug to the preparation of drugs for treating tumors, such as melanoma, lymphoma, leukemia, or breast cancer. This nanosystem exhibits good NO release levels under light irradiation. Cellular experiments have demonstrated its good antitumor effect, providing a new strategy for multimodal combined antitumor therapy.

The invention provides a Motixazotide-nitrogen mustard conjugate and a preparation method and application of a fluorescent probe of the Motixazotide-nitrogen mustard conjugate, and belongs to the field of polypeptide preparation and biological medicine. According to the present invention, a solid phase polypeptide synthesis method is adopted to covalently link a DNA alkylation reagent nitrogen mustard and a CXCR4 targeting peptide Motixazotide, and further couple with a fluorescent dye so as to successfully prepare a series of novel conjugates and fluorescent probes thereof; experiments prove that the Motixazotide-nitrogen mustard conjugate and the fluorescent probe thereof prepared by the invention can be used for remarkably improving the anti-tumor activity of nitrogen mustard and the targeting property of the nitrogen mustard to tumor cells. Meanwhile, the rhodamine B labeled dinitrogen mustard conjugate BCCR has a specific targeting effect on a CXCR4 receptor and a dual targeting effect on a tumor cell nucleus. The conjugate realizes real-time tracing of the whole process of tumor targeting, cell delivery and nuclear localization, and provides a powerful tool for curative effect evaluation and mechanism research, so that the conjugate has good clinical transformation prospect and application value.

The present invention discloses a nitrogen mustard-synergistic strontium ion antibacterial fabric, as well as its preparation method and use. An azo drug, 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide, is prepared using dopamine hydrochloride and N-phenyldiethanolamine. The drug is then coordinated with strontium ions on fabric fibers through in-situ growth to form nanoparticles. Upon contact with bacteria, the functionally coated fabric releases nitrogen mustard within the bacterial environment, forming a strong electrophilic alkylating agent within the cells. This covalently binds to electron-rich groups in DNA, RNA, and some enzymes, deactivating them and killing the bacteria. Furthermore, a large amount of strontium ions slowly released from the antibacterial fabric can be adsorbed on the surface of bacterial cell membranes, causing a voltage difference between the inside and outside of the cell membranes, weakening and rupturing the cell membranes. The strontium ions then enter the cells and hinder their formation and metabolism, thereby achieving a synergistic antibacterial effect.

The application provides a construction and application of a singlet oxygen-mechlorethamine synchronous delivery system, and belongs to the technical field of biological medicines.Based on the anticancer performance of singlet oxygen and mechlorethamine compounds and the overexpression of enzymes in a tumor microenvironment, an endoperoxide-mechlorethamine combined treatment molecule responding to azo reductase is designed and synthesized: the molecule plays a role in a specific tumor microenvironment, releases mechlorethamine and singlet oxygen, and produces specific damage to tumor cells.Further, the drug is wrapped in a liposome to improve the targeting and biological safety of the drug to tumor cells.Meanwhile, in vitro and tumor-bearing mouse experiments show that the molecule has great potential in cancer treatment.

The present invention is about a quinoline based aniline nitrogen mustard conjugates as anti-cancer agent. The present invention particularly relates to quinoline based aniline nitrogen mustard conjugates with anti-cancer activity and process for the preparation thereof. Formula (1)

The invention belongs to the field of medicines, and particularly discloses a light-activated chemotherapy medicine as well as a preparation method and application thereof. The light-activated chemotherapeutic drug comprises a therapeutically effective amount of a compound as shown in a formula (I) or pharmaceutically acceptable salts, esters, isomers and solvates thereof, and pharmaceutically acceptable auxiliary materials. According to the compound, a nitrogen mustard-containing group is coordinated into a ruthenium (II) complex, so that the nitrogen mustard-containing group is caged by the ruthenium (II) complex, the biological activity of the nitrogen mustard group is masked in a dark environment, good biocompatibility is shown, and the nitrogen mustard-containing group has good biocompatibility under a low-power visible light condition. The nitrogen mustard group ligand can be quickly and effectively released, the light-controllable accurate release of the nitrogen mustard medicine is realized, the toxic and side effects of the nitrogen mustard medicine in the treatment process are effectively reduced, and the treatment effect of the compound on cancers is improved. # imgabs0 #

The present invention belongs to the field of drug synthesis technology, and specifically provides a hypoxia-activated prodrug derivative and a synthesis method thereof. Using benzimidazole as raw material, (1-methyl-1H-imidazole-2-nitrile-5-yl)methanol and (1-methyl-1H-imidazole-2-nitrile-4-yl)methanol are obtained by ring opening, decarboxylation, esterification, iodination, bromine substitution, reduction, and cyano substitution; then it is condensed with bromoisophosphoramide nitrogen mustard to obtain N, N'-bis (2-bromoethyl) diaminophosphonic acid (1-methyl-1H-imidazole-2-nitrile-5-yl) methyl ester or N, N'-bis (2-bromoethyl) diaminophosphonic acid (1-methyl-1H-imidazole-2-nitrile-4-yl) methyl ester. After testing the inhibition rate of ovarian cancer cells, the inhibition rate of N, N'-bis (2-bromoethyl) diaminophosphonic acid (1-methyl-1H-imidazole-2-nitrile-5-yl) methyl ester of the present invention is comparable to that of TH-302.

The application relates to an N-oxygenase double-site mutant and application thereof in synthesis of nitrogen mustard, and belongs to the technical field of enzyme engineering. In order to solve the problem that the yield and the yield rate of N-oxygenase in catalyzing 2-aminoimidazole to synthesize nitrogen mustard are low in the prior art, the application provides an N-oxygenase double-site mutant with high catalytic activity. The yield and the yield rate of nitrogen mustard synthesized by the N-oxygenase double-site mutant are 1.68 mM and 42%, which are respectively increased by 2.8 times and 2.3 times compared with those of wild-type N-oxygenase, are the highest level of known biological synthesis of nitrogen mustard at present, and provide a new biological catalysis tool for synthesis of nitrogen mustard.

The application belongs to the technical field of analytical testing, and discloses a detection method of a nitrogen mustard-containing sophoridine chlorophenyl derivative. The purity of the derivative to-be-detected substance is detected by adopting an HPLC-DAD method combined with ion pair reagents. The control conditions of the HPLC-DAD include that the chromatographic column is a C18 column, the detection wavelength is 210-220 nm, the mobile phase A is 0.003-0.008 M sodium heptanesulfonate aqueous solution, and the mobile phase B is methanol. The peak type of R1 and R2 is best, the response value is high, and the baseline separation can be achieved with adjacent impurity peaks, the specificity is good, the detection limit is low, the precision is good, the stability is high, and the detection can be quickly and accurately realized.

This invention provides a method for preparing and applying a class of Motixafortide-nitrogen mustard conjugates and their fluorescent probes, belonging to the fields of peptide preparation and biomedicine. This invention utilizes a solid-phase peptide synthesis method to covalently link the DNA alkylating agent nitrogen mustard with the CXCR4 targeting peptide Motixafortide, and further couple it with a fluorescent dye, successfully preparing a series of novel conjugates and their fluorescent probes. Experimental verification shows that the Motixafortide-nitrogen mustard conjugates and their fluorescent probes prepared in this invention can significantly enhance the antitumor activity and targeting of nitrogen mustard to tumor cells. Simultaneously, the rhodamine B-labeled dinitrogen mustard conjugate BCCR exhibits specific targeting of the CXCR4 receptor and dual targeting of the tumor cell nucleus. These conjugates enable real-time tracking of the entire process of tumor targeting, cell delivery, and nuclear localization, providing a powerful tool for efficacy evaluation and mechanism research, thus possessing promising clinical translational prospects and application value.

The application belongs to the technical field of drug research and development, and particularly relates to a cyclophosphamide or ethylene imine prodrug compound, and further discloses the use thereof for preparing a liver-targeting alkylating agent. The compound disclosed in the application is based on traditional nitrogen mustard and derivatives thereof and ethylene imine alkylating agents, and is metabolically activated by a prodrug form through liver enzymes, further enhances the selectivity of the related compounds, reduces the influence on normal cells, and is metabolically activated by cytochrome P450 (CYP450) to release active ingredients, and has a good application prospect in treating liver-related cancers.

This invention discloses a near-infrared photoactivated nitrogen mustard drug compound, its preparation method, and its applications. The general structural formula of the near-infrared photoactivated nitrogen mustard drug compound is shown below: where R1 and R2 are both optionally selected from methyl, ethyl, n-propyl, n-butyl, n-pentyl, and n-hexyl. This compound reduces the toxic side effects of nitrogen mustard through a prodrug strategy. This compound utilizes the synergistic effect of nitrogen mustard chemotherapy and photodynamic therapy with a photosensitizer to effectively inhibit tumor growth. Simultaneously, the introduction of the photosensitizer imparts fluorescence changes before and after nitrogen mustard drug release, enabling visualization of drug release. This compound has broad application prospects in reducing drug toxicity and anti-tumor activity. The near-infrared photoactivated nitrogen mustard prodrug / drug preparation method provided by this invention is simple, uses inexpensive and readily available raw materials, has a simple synthesis process, and is easy to separate and purify, making it suitable for large-scale production and widespread application.

The invention discloses a preparation method of a sulfur dioxide gas synergistic nitrogen mustard antibacterial fabric, belonging to the technical field of fabric antibacterial. The preparation method is as follows: N-phenyldiethanolamine and phosphorus oxychloride are synthesized to obtain intermediate 1; intermediate 1 and p-aminobenzoic acid are synthesized to obtain intermediate 2; intermediate 2 and p-aminophenol are synthesized to obtain intermediate 3; intermediate 3 and 2,4-dinitrobenzenesulfonyl chloride are synthesized to obtain 4-(4-((4-bis(2-chloroethyl)amino)phenyl)diazenyl)benzamide)phenyl 2,4-dinitrobenzenesulfonate; 4-(4-((4-bis(2-chloroethyl)amino)phenyl)diazenyl)benzamide)phenyl 2,4-dinitrobenzenesulfonate, 2-methylimidazole and zinc nitrate hexahydrate are assembled into nanoparticles on the fabric to obtain a sulfur dioxide gas synergistic nitrogen mustard antibacterial fabric, and the antibacterial fabric can accelerate the decomposition of nanoparticles and improve the antibacterial effect.

The present invention provides a nitrogen mustard active probe and its application. The probe comprises a compound having the structure shown in the following formula. The present invention further provides a method for synthesizing the nitrogen mustard active probe and its application in preparing a nitrogen mustard marker or anti-tumor drug. Furthermore, a nitrogen mustard marker or anti-tumor drug containing the nitrogen mustard active probe as an active component is provided. The probe of the present invention can be used as a bioorthogonal labeling probe, particularly for labeling nitrogen mustard in tissues and cells, and for studying the toxicological mechanisms of nitrogen mustard in anti-tumor and immunosuppressive effects. The probe can be used to explore the direct protein targets of nitrogen mustard, contributing to a deeper understanding of its mechanism of action. The active probe itself has certain anti-tumor and immunosuppressive effects and can be used as an immunosuppressive and / or anti-tumor drug.

The present invention is about a quinoline based aniline nitrogen mustard conjugates as anti-cancer agent. The present invention particularly relates to quinoline based aniline nitrogen mustard conjugates with anti-cancer activity and process for the preparation thereof. Formula (1)

The invention discloses a nitrogen mustard substituted BODIPY phototherapy agent as well as a preparation method and application thereof, and relates to a medical phototherapy agent as well as a preparation method and application thereof. The molecular structure of the phototherapy agent takes BODIPY as a parent nucleus, nitrogen mustard groups are introduced to 3 and 5 sites, and an azo bond is taken as a photoresponse connecting bridge, so that photodynamic therapy, photothermal therapy and targeted release of nitrogen mustard chemotherapeutic drugs are realized, a three-mode synergistic anti-tumor effect is formed, the structural diversity of near-infrared first-area BODIPY dye is enriched, and the phototherapy agent has a good application prospect. And a new material basis is provided for deep application of the material in the fields of biology, material science and the like. The series of compounds have wide derivation development potential, and BODIPY dye molecules with various structures and novel functions can be further developed. The synthesis route is simple, the raw materials are easy to obtain, a new strategy is provided for developing a novel multifunctional phototherapy preparation, and the method has a good application prospect in the field of tumor collaborative treatment.

The invention discloses a hypoxia-responsive dendritic pegylated nitrogen mustard nano prodrug and application thereof, and belongs to the technical field of biological medicines. The invention designs and constructs a hypoxia-responsive dendritic pegylated nitrogen mustard nano prodrug to co-deliver nitrogen mustard and chlorin e6, and the prodrug contains a hypoxia-responsive azobenzene group and a ternary cross-linked pegylated dendritic drug conjugate which loads a chemotherapeutic drug CB through a covalent bond; under the condition of 650 nm near-infrared illumination, nano prodrug-loaded Ce6 releases active oxygen to kill tumor cells, consumes oxygen, increases the degree of hypoxia, the ternary crosslinking link is broken, and polyethylene glycol on the outer layer of the nano prodrug is removed, so that the intake of the nano prodrug by the tumor cells is increased, azobenzene is broken after the nano prodrug enters the tumor cells, and the nano prodrug can be absorbed by the tumor cells. And the chemotherapeutic drug CB is released, so that the photodynamic-chemotherapy combined therapy with enhanced tumor cell uptake is realized.

The present application relates to the technical field of chemical medicine, in particular to a kind of diamino pyrimidine compound containing phenyl nitrogen mustard fragment and its preparation method and application.A kind of diamino pyrimidine compound containing phenyl nitrogen mustard fragment is provided in the present application, its structural formula is as shown in formula (I).The compound is a new compound newly synthesized.The diamino pyrimidine compound containing phenyl nitrogen mustard fragment is novel in structure, has strong inhibitory effect on tumor cells, and has good application prospect in the preparation of antitumor drugs.

The invention belongs to the technical field of modernization of traditional Chinese medicines, and mainly relates to a novel camptothecin derivative as well as a preparation method and medical application thereof. Specifically, on the basis of structural optimization of a traditional Chinese medicine active ingredient camptothecin, 7-ethyl-10-hydroxycamptothecin (SN-38) is chemically modified through a bis (2-chloroethyl) carbamate group, and a novel derivative containing a nitrogen mustard pharmacophore and a camptothecin mother nucleus at the same time is designed and synthesized. And further introducing a phosphate group into the alcoholic hydroxyl group through phosphorylation modification or a salt forming reaction or forming inorganic acid salt to finally obtain the target compound as shown in the formula I. In-vivo and in-vitro experiments prove that the SN-38 derivative disclosed by the invention has the advantages of improving the anti-tumor effect, increasing the drug stability, reducing the toxic and side effects of the drug and the like.

The present invention discloses a hypoxia-responsive supramolecular polypeptide nanoprodrug and its preparation method and application. The hypoxia-responsive supramolecular polypeptide nanoprodrug is prepared from tetraaminoporphyrin-poly(L-lysine)-azobenzene nitrogen mustard and a novel water-soluble column [6] aromatic hydrocarbon AWBpP6. The hypoxia-responsive supramolecular polypeptide nanoprodrug of the present invention increases drug loading efficiency, reduces the toxic side effects of nanomedicines, and improves stability in the form of polymer-prodrug. Under near-infrared light conditions, the porphyrin in the prodrug particles can not only release reactive oxygen species to achieve photodynamic therapy, but also consume oxygen in the process, thereby enhancing chemotherapy mediated by the hypoxic environment. By combining chemotherapy and photodynamic therapy in a dual combination therapy, the effect of anti-tumor treatment is greatly improved.