73 results about "Camptothecin" patented technology

The present invention relates to camptothecin compounds with antitumor activity, their preparation methods and their applications.Specifically, the present invention relates to the following compounds or their pharma- ceutically acceptable forms, their pharmaceutical compositions, their preparation methods and their uses.The compounds can be used as drugs to treat diseases in abnormal cell proliferation. JPEG2024506819000283.jpg44149

Described is an antibody-drug conjugate (ADC) having the formula A-L, wherein A is an antibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a topoisomerase I inhibitor which is cell-permeable, e.g., a camptothecin cytotoxic molecule which is cell-permeable; as a second payload a topoisomerase I inhibitor which is not cell-permeable, e..g., a camptothecin cytotoxic molecule which is not cell-permeable; and as a as a third payload a toxin or a cytotoxin, e.g., an auristatin such asMMAE (Monomethyl auristatin E). Moreover, described is a pharmaceutical composition comprising said ADC and at least one pharmaceutically acceptable ingredient. Further, described method of treating a patient suffering from, being at risk of developing, and / or being diagnosed for a neoplastic disease.

The invention provides a planting method for promoting synthesis of camptothecin and derivatives thereof from nothapodytes pittosporoides. The planting method comprises the following steps: planting a plurality of nothapodytes pittosporoides trees in a planting field; organic fertilizer is applied to the multiple planted nothapodytes pittosporoides trees every first preset time; the planted nothapodytes pittosporoides trees are soaked with cold water for several days, and temperature and water stress is carried out; removing the nothapodytes nothapodytes which do not survive after water stress; introducing microorganisms every second preset time to adjust rhizosphere microorganisms of the nothapodytes pittosporoides trees so as to carry out microorganism stress; watering is stopped in autumn, so that the survival nothapodytes nothapodytes trees are subjected to sunlight stress, and the survival nothapodytes nothapodytes trees enter the sunlight stress period; in the sunlight stress period, synthesis of terpene indole alkaloid of rhizosphere microorganisms is activated, and synthesis of camptothecin and derivatives of camptothecin from nothapodytes pittosporoides is promoted; wherein except for the sunlight stress period, the environment temperature of the planting field is kept at 5 DEG C or above, and the environment humidity is kept at 63%-78%.

A camptothecin conjugate and a preparation method thereof. The camptothecin conjugate has excellent drug activity and kinetic characteristics, and is suitable for preparing a drug for treating tumor-related diseases.

The invention belongs to the field of pesticides, and particularly relates to a botanical weeding composition which comprises an active component A and an active component B, the active component A is paeonol or artesunate, the active component B is 7-ethyl camptothecin, and the mass ratio of the active component A to the active component B is (1: 10)-(10: 1). The botanical herbicidal composition has excellent herbicidal activity on barnyard grass, nutgrass flatsedge and sticktight due to the synergistic effect of the two components, and can be directly developed into a botanical herbicidal active component composition for preventing and controlling gramineae, nutgrass flatsedge and broadleaf weeds in farmland.

The present disclosure relates to a Camptothecin compound having anti-tumor activity, a preparation method therefor, and an application thereof. Specifically, the present disclosure relates to a compound as shown below or a pharmaceutically acceptable form thereof, a pharmaceutical composition thereof, a preparation method therefor, and a use thereof. The compound can be used as a drug for treating diseases in abnormal cell proliferation,

Provided is a method for preparing a camptothecin conjugate. The new method for preparing a camptothecin conjugate exhibits one or more effects selected from the group consisting of a high yield, a simple purification process, low impurities, suitability for industrial production, and high stability.

The invention provides a paclitaxel precursor nano-drug as well as a preparation method and application thereof, and belongs to the technical field of medicinal chemistry. Comprising a paclitaxel dimer prodrug and 7-ethyl10-hydroxy-camptothecin loaded on the paclitaxel dimer prodrug. According to the invention, a paclitaxel dimer prodrug is used as a self-assembly monomer to construct a PTX-SN38 synergistic treatment nano system, and the system has the advantages of dispersibility in water, biocompatibility, tumor specific response, synergistic treatment and the like, and can effectively solve the limitation of paclitaxel and SN38 in anti-tumor treatment.

The invention provides a GSH (glutathione) reduction response type targeted nano-drug based on chondroitin sulfate as well as a preparation method and application of the GSH reduction response type targeted nano-drug. Chondroitin sulfate with CD44 receptor targeting ability and an anti-cancer drug camptothecin are covalently linked through a disulfide bond sensitive to GSH, and the constructed novel targeting nano-drug can accurately recognize human colorectal cancer tumor cells highly expressed by a CD44 receptor in a targeting manner. Meanwhile, the high-concentration glutathione at the tumor site can oxidize and reduce the disulfide bond to cause the fracture of AC-CPT NPs, so that the effective release of the camptothecin medicine at the tumor site is realized, and the anti-tumor effect is further enhanced. The reduction response type targeting nano-drug prepared by the invention solves the problems of poor targeting and biological solubility and limited treatment effect of the traditional anti-cancer drug camptothecin, and provides an innovative strategy for realizing accurate targeting and efficient treatment of cancers.

The invention relates to the technical field of textile processing, and discloses a production process for improving the stain-resistant function of a sweater, the process comprises five steps of pretreatment, stain-resistant solution preparation, dipping treatment, pre-drying curing and finished product treatment: firstly, dedusting, washing, dehydrating and pre-drying a sweater blank to remove impurities; mixing and stirring the modified camptothecin, fatty alcohol-polyoxyethylene ether, water, ethylene glycol and perfluorohexyl ethyl alcohol according to a specific weight part ratio to prepare a stain-resistant solution; then, the pretreated blank is soaked in a stain-resistant solution, and stain-resistant components are fully permeated through constant-temperature soaking, regular stirring and ultrasonic treatment; then, through gradient heating pre-drying and curing, the stain-resistant components are firmly attached to the surfaces of the fibers; and finally, performing finished product treatment such as cooling and shaping to obtain the stain-resistant sweater. The finished sweater produced by the process has a lasting stain-resistant effect, can keep the original properties such as warm keeping and softness of natural fibers, and solves the problem that the traditional sweater is easy to stain.

Described is an antibody-drug conjugate (ADC) having the formula A-L, wherein A is an antibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a topoisomerase I inhibitor which is cell-permeable, preferably a camptothecin cytotoxic molecule which is cell-permeable; and as a second payload a topoisomerase I inhibitor which is not cell-permeable, preferably a camptothecin cytotoxic molecule which is not cell-permeable. Moreover, described is a pharmaceutical composition comprising said ADC and at least one pharmaceutically acceptable ingredient. Further, described is an ADC for use in a method of treating a patient suffering from, being at risk of developing, and / or being diagnosed for a neoplastic disease.

The application discloses a kind of endoplasmic reticulum of tumor cell can be targeted N -(2-hydroxypropyl) methacrylamide (HPMA) polymer-drug conjugate. The chemotherapeutic drug carried by the HPMA polymer is at least one of doxorubicin, epirubicin, pirarubicin, cisplatin, oxaliplatin, camptothecin, paclitaxel, gemcitabine, methotrexate, vinblastine, mitoxantrone, irinotecan, and the linker for connecting the drug and the HPMA polymer is at least one of hydrazone bond, amide bond, ester bond, disulfide bond, and ketosulfenyl bond. The HPMA polymer-drug conjugate targets the drug to the endoplasmic reticulum through receptor-ligand interaction, can cause severe endoplasmic reticulum stress, thereby transporting a large amount of calnexin to the tumor cell membrane surface, greatly improving the immunogenicity of tumor cells, and promoting tumor immunotherapy.

Provided herein are compounds, including compounds of Formula (I''), (I'), and (I), and a pharmaceutically acceptable salts thereof, which comprise a fibroblast activating protein (FAP)-cleavable moiety and are capable of delivering a camptothecin to FAP-expressing tissues (eg., cancers). Also provided herein are pharmaceutical compositions and kits comprising the same, as well as methods of using the same.

The present disclosure provides antibody-drug conjugate (ADC) structures where the antibody-drug conjugate includes a camptothecine or a camptothecine derivative linked to a polypeptide (e.g., an antibody) through a linker. In addition, the disclosure also encompasses compounds and methods for production of such conjugates, as well as methods of using the conjugates.

The invention discloses a camptothecin compound and a conjugate thereof. The invention provides a compound as shown in a formula I, a solvate of the compound, a pharmaceutically acceptable salt of the compound or a solvate of the pharmaceutically acceptable salt of the compound. The camptothecin compound disclosed by the invention has better anti-tumor activity, and the antibody drug conjugate prepared based on the camptothecin compound also has better anti-tumor activity.

The application relates to a kind of SN38-fatty alcohol prodrugs and its self-assembly nanoparticles and application, belong to the field of new excipients and new dosage forms of pharmaceutical preparations, and relates to a kind of 7-ethyl-10-hydroxy camptothecin prodrug antitumor preparation, specifically to the construction of SN38-fatty alcohol prodrug and its self-assembly nanoparticles containing the prodrug, and its application as a drug delivery system in the preparation of antitumor drugs.The structure general formula (I) of SN38-fatty alcohol prodrug or its pharmaceutically acceptable salt is as follows: wherein, n, R, X are described in the claims and the specification.The SN38-fatty alcohol prodrug of the application can be self-assembled into nanoparticles, can effectively improve curative effect, reduce its toxic side effect.

The invention discloses a method for synthesizing a camptothecin chiral precursor with high enantioselectivity, and belongs to the field of organic synthesis. In the invention, the preparation of a chiral precursor amide compound of camptothecin comprises the following steps: synthesizing corresponding aryl (E)-2-ethylbutyl-2-olefine acid ester, mixing the aryl (E)-2-ethylbutyl-2-olefine acid ester with a phase transfer catalyst derived from cinchona alkaloid in an organic solvent, sequentially adding acid, potassium permanganate and a small amount of potassium fluoride solution for reaction, and after the reaction is finished, performing suction filtration to obtain the chiral precursor amide compound of camptothecin. Carrying out amine ester exchange with diethylamine; and evaporating the solvent, and quickly purifying by using a silica gel column to obtain the camptothecin precursor chiral amide compound with high enantioselectivity. The invention aims at providing a new thought and a new method for total synthesis of camptothecin based on a camptothecin chiral precursor reported in literatures, and broadens a synthesis route for synthesizing camptothecin.

This invention discloses a novel class of peptides for targeted cancer therapy and their corresponding drug or fluorescent dye conjugates, belonging to the field of biomedical technology. These peptides are designed based on the optimized structure of natural LHRH-III, enabling them to specifically bind to and efficiently internalize into tumor cells overexpressing luteinizing hormone-releasing hormone receptor (LHRH-R). After fluorescent conjugation, their targeting ability against 4T1 cells is comparable to that of the classic peptide [D-Lys]. 6 The [-LHRH-I] peptide exhibits comparable to or superior performance and significantly improves cellular internalization efficiency. In vivo distribution studies have shown that its liver accumulation is significantly reduced compared to the control group, effectively lowering the risk of hepatotoxicity. Furthermore, by conjugating the targeting peptide with antitumor drugs (such as camptothecin or doxorubicin) via disulfide linkers, the resulting peptide-drug conjugates (PDCs) demonstrate excellent responsive drug release characteristics and good in vitro and in vivo antitumor activity. The peptides and conjugates provided by this invention have potential application value in cancer targeted therapy and diagnosis with high specificity and low toxicity.

The invention discloses a camptothecin-phospholipid conjugate self-assembled nanotube and a preparation method and application thereof, the camptothecin-phospholipid conjugate self-assembled nanotube is formed by self-assembling a phospholipid-camptothecin conjugate, the supermolecule nanotube is provided with a hollow inner cavity, and azide functional groups are distributed on the surface of the inner cavity. Different alkynyl-modified functional molecules (such as fluorescent probes, targeting ligands and other drugs) can be flexibly grafted on the inner cavity click chemical platform of the nanotube. The strategy is especially suitable for refractory tumors (such as triple negative breast cancer) requiring precise drug proportion and synergistic administration, and has wide clinical application potential.

The present invention concerns antibody-conjugate having general structure (2):wherein AB is an antibody capable of targeting Trop-2-expressing tumours and D is selected from the group consisting of taxanes, anthracyclines, camptothecins, epothilones, mytomycins, combretastatins, vinca alkaloids, maytansinoids, enediynes such as calicheamicins, duocarmycins, tubulysins, amatoxins, bleomycins, dolastatins and auristatins, pyrrolobenzodiazepine dimers, indolinobenzodiazepine dimers, radioisotopes, therapeutic proteins and peptides (or fragments thereof), kinase inhibitors, MEK inhibitors, KSP inhibitors, and analogues or prodrugs thereof. These antibody-conjugates exhibit an improved therapeutic index. The invention further concerns a process for preparing the antibody-conjugate according to the invention, a method for targeting Trop-2-expressing cells, medical uses of the antibody-conjugates according to the invention.

We provide camptothecin-based pharmaceuticals and their antibody conjugates. [Solution] A compound of the following formula I and its antibody complex are provided. JPEG2026086826000042.jpg62170 (In formula I, R1 and R2 are independently a C1-C3 alkyl group, -H, -CF3, aryl group, heteroaryl group, etc.)

The application discloses a preparation method of a medical intermediate (R)-7-ethyl camptothecin, and relates to the field of chemical medicine synthesis. The application comprises the following contents: (R)-4-ethyl-4-hydroxy-7,8-dihydro-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione (formula A) and 1-(2-aminophenyl)propan-1-one (formula B) are used as main raw materials, a target compound (R)-7-ethyl camptothecin is obtained through reaction in an organic solvent under the action of a catalyst. The application provides a novel preparation method of the medical intermediate (R)-7-ethyl camptothecin, and the preparation method is simple, stable, high in yield, and suitable for industrial production.

The invention provides a preparation method and application of a camptothecin-elastin-like peptide conjugate capable of being self-assembled, and belongs to the field of nano-drugs. The camptothecin self-assembled prodrug is synthesized through a drug-connexon conjugate, and the obtained camptothecin self-assembled prodrug can be self-assembled in an aqueous solution through pi-pi interaction among camptothecin molecules to form a one-dimensional nanotube structure. The camptothecin self-assembled prodrug adopts the design concept of self-assembled prodrug, camptothecin is used as a structural unit, the camptothecin self-assembled prodrug with hydrophilic and hydrophobic balance is obtained by simply connecting hydrophilic polypeptides with different sequences, the prodrug has high drug loading capacity and improved solubility, and a clearly defined one-dimensional nano structure can be formed by simply dissolving the prodrug in water. The method has the advantages that the method is simple and easy to operate, the repeatability is excellent, the tumor inhibition effect is obviously superior to that of clinical medicine irritecan in in-vivo anti-tumor treatment, nearly 90% of tumor growth inhibition can be achieved, the biological safety is good, and the method has important significance in nano-medicine production preparation and clinical conversion.

The invention discloses an application of brucein D and Vinetoram in preparation of a medicine for treating acute or drug-resistant myelogenous leukemia. Through a large number of experimental screening, the brucein D and the Venotocork are combined for medication, and the test result shows that the brucein D and the Venotocork act on different targets and different signal channels of AML cells to generate a remarkable synergistic anti-tumor effect, and after the brucein D and the Venotocork are combined, the proliferation inhibition and apoptosis induction effects on the AML cells can be directly enhanced, and the anti-tumor effect of the Venotocork D and the AML cells can be improved. The compound can also reverse the drug resistance possibly occurring when the Vinetoram is singly used, and also has a remarkable killing effect on chemotherapy drug-resistant AML cells at the same time. The composition provided by the invention can reduce the dosage of antitumor drugs, reduce drug resistance, reduce adverse reactions and improve the life quality of patients, and has important application prospects.

The invention provides a 7-ethyl-10-hydroxycamptothecin drug precursor with fluorescence activity and a preparation method and use thereof. The method involves that a carboxyl group of a boron dipyrromethene dye molecule is condensed with a hydroxyl group at the 10 position of 7-ethyl-10-hydroxycamptothecin, yielding a 7-ethyl-10-hydroxy-camptothecin drug precursor (BDP-SN38) with fluorescent activity. BDP-SN38 shows good solubility and stability in most pharmaceutically acceptable solvents. Compared with SN38, BDP-SN38 exhibits comparable antitumor activity, has high tumor uptake capacity, and produces strong green fluorescence with the excitation of visible light, thus providing fluorescence-guided bioimaging and further treatment of residual tumors after drug treatment, and having good application prospects in the research of integrated diagnosis and treatment and effective tumor treatment.

The invention relates to a camptothecin compound and a conjugate thereof, or a tautomer, an enantiomer and a diastereoisomer thereof, or a mixture form thereof, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutical composition, a preparation method and an application thereof. The compounds and conjugates can be used for treating proliferative diseases associated with abnormal cell activity.

The application discloses a preparation method and application of a chemotherapy drug and small interfering RNA tumor-targeting co-delivery nano-therapeutic system, and relates to construction and preparation of a tumor-targeting nano-therapeutic system co-loading a chemotherapy drug, camptothecin, and small interfering RNA (siRac1) targeting Rac1. The application uses N,N-dimethylethylenediamine modified mesoporous polydopamine, loads camptothecin and siRac1, and is then modified by hyaluronic acid to obtain a co-delivery nano-therapeutic system with tumor active targeting. Compared with traditional chemotherapy drugs, camptothecin, the application can realize tumor active targeting drug delivery, and can inhibit tumor chemotherapy resistance mediated by Rac1 by silencing the expression of Rac1 through siRac1, so that the sensitivity of drug-resistant tumor cells to the chemotherapy drug, camptothecin, is restored, tumor drug resistance is reversed, the treatment effect of drug-resistant triple-negative drug-resistant breast cancer is significantly improved, and the application has a good clinical application prospect.

The invention discloses a drug delivery nano system based on ROS response as well as a preparation method and application of the drug delivery nano system. The drug delivery nano system comprises nanoparticles and a camptothecin-5-fluorodeoxyuridine prodrug, wherein the nanoparticles are formed by self-assembly of an amphiphilic high-molecular polymer HA-IR-780 with a photosensitive characteristic, and the camptothecin-5-fluorodeoxyuridine prodrug is wrapped in the nanoparticles; and the surface of the drug delivery nano system is modified with a lipid-polyethylene glycol material. When the drug delivery nano-system is applied to preparation of breast cancer drugs, the drug delivery nano-system can be enriched at a tumor site depending on the passive targeting effect of the EPR effect of the drug delivery nano-system, breast cancer chemotherapy / PDT / PTT / combined treatment can be achieved, and the effects of reducing toxicity and enhancing efficacy are achieved to a certain extent.

This invention relates to the preparation of 10-trifluoromethoxycamptothecin compounds and their use in antitumor drugs. The structural formula of these compounds is shown below. In vitro cytotoxicity screening results show that 10-trifluoromethoxycamptothecin compounds possess broad-spectrum antitumor activity, exhibiting strong inhibitory activity against human hepatocellular carcinoma cells (HepG2), human non-small cell lung cancer cells (A549), human colon cancer cells (SW480), human cholangiocarcinoma cells (QBC939), human breast cancer cells (MCF-7), human pancreatic cancer cells (PANC-1), and human pancreatic cancer cells (BxPC-3). Compounds 10-trifluoromethoxycamptothecin I and 7-ethyl-10-trifluoromethoxycamptothecin II showed strong inhibitory effects against all seven tested tumor cell lines, with IC50 values ​​exceeding 100%. 50 The concentrations were 0.913–0.0661 μM and 4.932–0.0578 μM, respectively, both significantly superior to the control drug topotecan. Among them, compounds I and II exhibited the strongest inhibitory activity against the BxPC-3 cell line, with IC50 values ​​of [missing value]. 50 The values ​​were 0.0661±0.0065μM and 0.0578±0.0043μM, respectively. Therefore, 10-trifluoromethoxycamptothecin compounds hold promise for development into a novel antitumor drug.

The application provides a kind of pharmaceutical composition and its preparation method and application, and the active ingredient of pharmaceutical composition is composed of camptothecin, 9-methoxy camptothecin and camptothecin glucoside, and the preparation method comprises: the plant part of Maybium ferrugineum is cleaned, and the pretreated raw material is obtained by drying to change mature and crushing at the first preset temperature;The pretreated raw material is extracted by reflux extraction with the first extraction solvent for the first extraction times, and each extraction is carried out for the first preset time, and the extract obtained by each extraction is combined and concentrated to obtain extract;The extract is dispersed with water, sequentially extracted with petroleum ether, ethyl acetate, and water-saturated n-butanol is extracted to obtain total glycoside;Total glycoside is purified to collect the fraction containing camptothecin, 9-methoxy camptothecin and camptothecin glucoside, and concentrated and crystallized to obtain the pharmaceutical composition.The pharmaceutical composition of the application has significant synergistic antitumor effect, and provides an efficient and low-toxicity treatment option for clinical use.