36 results about "Cyclen" patented technology

Cyclen-based chelates can be used as contrast agents for multi-modal imaging of tissue cells. The cyclen-based chelates are preferably polyazamacrocyclic molecules formed from 1,4,7,10 tetraazacyclododecane (“cyclen”) having varying chelating ions, phosphoester chains, and light harvesting moieties. By changing the chelating ion, phosphoester chain length and / or the light harvesting moiety different imaging techniques, such as MRI, CT, fluorescence and absorption, x-ray and NIR, may be employed to image the tissue cells. Additionally, the cyclen-based chelates may be conjugated to provide for site-specific delivery of the cyclen-based chelate to the desired tissue cells. The cyclen-based chelates may also be delivered to the tissue cells by attaching the cyclen-based chelates to a polymeric delivery vehicle. Although these cyclen-based chelates have a wide variety of application, the preferred use is for imaging of cancer cells, such as brain cancer, for improving resection of a cancerous tissue.

Cyclen-based chelates can be used as contrast agents for multi-modal imaging of tissue cells. The cyclen-based chelates are preferably polyazamacrocyclic molecules formed from 1,4,7,10 tetraazacyclododecane (“cyclen”) having varying chelating ions, phosphoester chains, and light harvesting moieties. By changing the chelating ion, phosphoester chain length and / or the light harvesting moiety different imaging techniques, such as MRI, CT, fluorescence and absorption, x-ray and NIR, may be employed to image the tissue cells. Additionally, the cyclen-based chelates may be conjugated to provide for site-specific delivery of the cyclen-based chelate to the desired tissue cells. The cyclen-based chelates may also be delivered to the tissue cells by attaching the cyclen-based to a polymeric delivery vehicle. Although these cyclen-based chelates have a wide variety of application, the preferred use is for imaging of cancer cells, such as brain cancer, for improving resection of a cancerous tissue.

Cyclen-based chelates can be used as contrast agents for multi-modal imaging of tissue cells. The cyclen-based chelates are preferably polyazamacrocyclic molecules formed from 1,4,7,10 tetraazacyclododecane (“cyclen”) having varying chelating ions, phosphoester chains, and light harvesting moieties. By changing the chelating ion, phosphoester chain length and / or the light harvesting moiety different imaging techniques, such as MRI, CT, fluorescence and absorption, x-ray and NIR, may be employed to image the tissue cells. Additionally, the cyclen-based chelates may be conjugated to provide for site-specific delivery of the cyclen-based chelate to the desired tissue cells. The cyclen-based chelates may also be delivered to the tissue cells by attaching the cyclen-based to a polymeric delivery vehicle. Although these cyclen-based chelates have a wide variety of application, the preferred use is for imaging of cancer cells, such as brain cancer, for improving resection of a cancerous tissue.

The invention relates to a preparation method of a macrocyclic chelating agent and an intermediate thereof, particularly to a preparation method of gadoteridol, gadobutrol and intermediates of gadoteridol and gadobutrol thereof. According to the method of the invention, high-purity t-Bu-DO3A can be simply and conveniently obtained from cyclen in one step, and gadoteridol or gadobutrol is obtainedthrough subsequent related reaction and purification; and the high purity of the final product is achieved by controlling the each link of the process so as to achieve the medicinal standard, the purification step of ion exchange chromatography is not needed, the operation is simple and convenient, the preparation is easy, the yield is high, and the method is particularly suitable for the requirements of industrial production.

The present invention relates to a method for preparing a bifunctional chelator for lanthanide. The method comprises the steps of providing a starting material which has an amino and carboxyl group; protecting the amino with an amino protecting group and the carboxyl with a carboxyl protecting group to produce a protected compound; reacting the protected compound with cyclen to generate a monoalkylated cyclen; reacting the monoalkylated cyclone with an activated compound to generated tetra-alkylated cyclone; removing the amino protecting group with a first protecting group removal reagent; and removing the carboxyl protecting groups with a second protecting group removal reagent to yield a bifunctional chelator having three more carboxyl groups and one or more amino groups.

The invention discloses a preparation method of 1,4,7,10-tetraazacyclododecane-1,4,7-10-tetraacetic acid (DOTA). The preparation method includes the steps of in water phase, subjecting 1,4,7,10-tetraazacyclododecane (cyclen) and XCH2COOR to alkylation reaction under the action of an acid-binding agent; adjusting pH to isolate crude DOTA; recrystallizing. The preparation method is suitable for large-scale industrial production of DOTA; the whole process has no need for purification by ion exchange resin and low-temperature freezing; the product yield s high; the product purity is 99.0% and above; single impurity content is < / =0.05%; residue on ignition is <0.10%; the preparation method meets the quality standard for bulk pharmaceutical chemicals.

The present invention relates to a process for preparing a macrocyclic ligand and for producing a pharmaceutical liquid formulation comprising a complex of said ligand with a lanthanide or similar compounds. The macrocyclic ligand of the present invention is a derivative of tetraaza macrocycles such as 1,4,7,10-tetraazacyclododecane (cyclen), 1,4,7,10-tetrazacyclotridecan (homocyclen) and 1,4,8,11-tetraazacyclotetradecane (cyclam), such as DOTA, TRITA, TETA, DOTMA, TCE-DOTA, DOTA-pNB, D03A, HP-D03A, D03A-butrol, D03MA, ODOTRA, D03A-L2, DOTP, DOTMP, DO2a, THP, THED, DOTAM, DOTTA. The preferred lanthanide and similar compounds are Gadolinium (Gd), Yttrium (Y) and Terbium (Tb). The process of the present invention aims to obtain an accurate balance between the ligand and the lanthanide, and to avoid the presence of free lanthanide in said formulation, by calculating the necessary amount of ligand for a formulation batch, measuring the moisture content of a sample of the material in said batch, calculating the total amount of moisture present of the batch and calculating the total amount of material which is required to prepare the batch size. In this way, the production of a pharmaceutical liquid formulation comprising a complex of a macrocyclic ligand with lanthanide is more accurate, faster and easier. The present invention is thus useful for the production of pharmaceutical liquid formulations comprising a complex of a macrocyclic ligand with a lanthanide, which can be used as contrast agents for magnetic resonance imaging.

The invention discloses a novel chelate resin containing tetraazacyclo and a preparation method of chelate resin, and belongs to the technical field of resin synthesis. The method comprises the following steps: modifying chloromethylate crosslinked polystyrene microsphere (PsCl) by using 1,4,7,10-tetraazacyclodocecane (Cyclen) so as to prepare a novel aza-crown ether resin Ps-Cy, wherein the highest full exchange capacity can achieve 5.3mmol / g. The adsorption of the Ps-Cy to Cu(II) indicates that the maximum adsorption quantity achieves 158.9mg / g. The crosslinked polystyrene microsphere is used as a substrate and the cyclic polyamine compound Cyclen is used as functional group, the substrate is connected with the functional group by using a covalent bond through methylene, the resin structure is stable, the adsorption capacity to metal ion is strong, the adsorption quantity fluctuation is small, and the resin can be repeatedly used.

The present invention provides a compound for restoring contaminated soil or contaminated water for the removal of heavy metals and formaldehyde wherein the compound includes at least one selected from a trientine or a trientine derivative represented by following formula 1, a cyclen or a cyclen derivative represented by following formula 2, and a cyclam or cyclam derivative represented by following formula 3 as an active ingredient.

The invention relates to an improved process for preparation of protected DO3A, such as DO3A-tri-t-butyl ester (1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid tri-t-butyl ester). The compound is prepared as a salt. The process includes a work-up procedure giving DO3A-tri-t-butyl ester as a salt of excellent purity.

The present invention provides a detergent composition for removing heavy metals and formaldehyde, comprising at least one selected from the group consisting of trientine or trientine derivative of Formula (1), cyclen or cyclen derivative of Formula (2), cyclam or cyclam derivative of Formula (3), and a salt thereof.

The invention provides a preparation method of cycleanine, and belongs to the technical field of production and preparation of fine chemicals. The method comprises the following steps: 1) adding a solvent, a ring extender and an acid-binding catalyst into an intermediate bisimidazoline, and performing a reaction in an inert gas atmosphere for a period of time; 2) performing vacuumizing after the reaction is finished in order to remove light components, then adding water and an alkaline catalyst, raising the temperature, performing a reaction for a period of time, and performing vacuumizing toremove the light components; and 3) adding toluene, filtering out a product liquid while hot, and finally performing recrystallization with water-toluene to obtain the cycleanine final product. The intermediate bisimidazoline is prepared by taking toluene as a solvent and triethylenetetramine as a substrate, dropwise adding N,N'-dimethylformamide dimethyl acetal, and performing vacuumizing after the raw materials are dropwise added to extract light components so as to obtain a turbid liquid which is the intermediate bisimidazoline. A single kettle or a multi-kettle combined form can be adoptedin the preparation process of cycleanine, so that the one-time investment cost is reduced; and the solvent has the characteristics of low dosage, recycling realization and low loss.

The invention relates to an improved process for preparation of protected DO3A, such as DO3A-tri-t-butyl ester (1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid tri-t-butyl ester). The compound is prepared as a salt. The process includes a work-up procedure giving DO3A-tri-t-butyl ester as a salt of excellent purity.

The present invention provides a detergent composition for removing heavy metals and formaldehyde, comprising at least one selected from the group consisting of trientine or trientine derivative of Formula (1), cyclen or cyclen derivative of Formula (2), cyclam or cyclam derivative of Formula (3), and a salt thereof.

The invention discloses a preparation method of high-purity trigonine. The present invention uses diethylenetriamine and N-benzyldiacetaldehyde amine as main raw materials, adds desiccant, absorbs the water produced, promotes the generation of imine, and at the same time feeds hydrogen to quickly reduce imine to avoid the decomposition of imine. The reaction is more thorough. The method has the advantages of simple steps, low cost, high yield, low requirement on equipment, environmental protection and suitability for industrialized production.

The invention provides a preparation method of high field gadobutrol. Cycleanine monoformaldehyde is used as a raw material, alkylation reaction is carried out with tert-butyl bromoacetate, then the alkylation product is hydrolyzed, and tricarboxylate intermediate is obtained; the tricarboxylate intermediate and 4,4-dimethyl-3,5,8-three oxygen bicyclo [5.1.0] octane react, then complex reaction ofthe reaction product and gadolinium oxide is carried out, and gadobutrol with higher purity and good yield is obtained.

A directly synthetic method for preparing tris-alkylated 1,4,7,10-tetraazacyclododecanes by the reactions of 1,4,7,10-tetraazacyclododecane (cyclen) and appropriate electrophiles is accomplished in high yield. The method provides operational convenience, starting material availability, cost economy, atom efficiency and reaction insensitivity to temperature, moisture, and concentrations of starting materials.

The invention discloses a preparation method of cyclen and an intermediate thereof, specifically a preparation method of a compound as shown in a formula 4. The method comprises the following step: in water, carrying out a reduction reaction as shown in the specification on a compound as shown in a formula 3 and hydrazine hydrate, wherein X is phosphoric acid or sulfuric acid, when X is phosphoric acid, n is 4 / 3, and when X is sulfuric acid, n is 2. The preparation method has the advantages of low cost, simple operation, easy purification of intermediates and products, high yield and purity, and suitableness for industrial production.

Cyclen based compounds of general formula (I) are disclosed. X is nitrogen and Y, Z are —CH—, or X, Z are —CH— and Y is nitrogen, or X, Y are —CH— and Z is nitrogen. R1 is independently selected from H; COOH; benzyloxycarbonyl; fluorenylmethyloxycarbonyl; tert-butoxycarbonyl; methylcarbonyl; trifluoromethylcarbonyl; benzyl; triphenylmethyl; tosyl; mesyl; benzyloxymethyl; phenylsulfonyl; ethoxycarbonyl; 2,2,2-trichloroethyloxycarbonyl; methoxycarbonyl; methoxymethyloxycarbonyl; R2 is selected from H; methylcarbonyl; tert-butyldimethylsilyl; (C1-C4)alkyl; R3 is independently selected from H; (C1-C6)alkyl.