129 results about "Camptothecin derivative" patented technology

The invention provides a 9-hydroxycamptothecin synthetase and a method for synthesizing the 9-hydroxycamptothecin. The invention discloses the 9-hydroxycamptothecin synthetase for the first time, and establishes a method for producing the 9-hydroxycamptothecin. According to the technical scheme, biological synthesis of the 9-hydroxycamptothecin is achieved, and a new way is provided for producing camptothecin derivatives based on strategies such as synthetic biology.

The present invention discloses a preparation method of camptothecin derivatives. The present invention provides a preparation method of a compound of formula 7, which comprises the following steps: in an organic solvent, the compound of formula 6 is subjected to a deprotection reaction with methanesulfonic acid to obtain the compound of formula 7. The preparation method of the present invention uses a small amount of solvent during post-treatment, is easy to filter, the obtained product is off-white, the product purity and yield are higher, and it is suitable for industrial production. The recrystallization mother liquor obtained from the deprotection reaction is easier to recover, greatly reducing the raw material cost.

The present disclosure relates to a ligand-drug conjugate of a novel structure or a pharmaceutically acceptable salt thereof. Specifically, the present disclosure provides a ligand-drug conjugate having a structural general formula represented by Pc-(L-D)n or a pharmaceutically acceptable salt thereof, a method for preparing same, a pharmaceutical composition comprising the conjugate, and use thereof in treating a tumor.

Disclosed in present invention are a novel cleavable linker compound as shown in formula (1) for a prodrug delivery system, and a pharmaceutically acceptable salt, solvate, polymorph or isomer thereof. Further disclosed are a prodrug compound as shown in formula (J) and formula (L) formed by covalently bonding an albumin or antibody to a camptothecin derivative by means of a novel linker compound, and a pharmaceutically acceptable salt, solvate, polymorph or isomer thereof. Further disclosed are a synthesis method for the compound, and a preparation method for the compound in an enzyme release prodrug system. Further disclosed are a use of the compound in preparation of an anti-tumor drug, and a use of the compound in preparation of an albumin-bound anti-tumor drug or antibody-drug conjugate. The present invention innovatively proposes a structure in which a trigger fragment in the compound is linked to the novel linker by means of p-hydroxyl or para-amino, an active drug is linked to the novel linker by means of the hydroxyl part of the active drug, and a modified fragment is linked to the novel linker by means of an amino group.

The present disclosure is directed toward drugs or toxins; drug conjugates comprising said drugs or toxins and a cleavable linker; and conjugates comprising said drugs or toxins, cleavable linkers, and cell-binding groups. The present disclosure also relates to methods of treating cancers, autoimmune diseases, and inflammatory diseases using the compounds and conjugates of the disclosure.

The invention discloses a camptothecin derivative compound and application thereof, and belongs to the technical field of medicinal chemistry. The structural formula of the camptothecin derivative compound is as shown in formula (1), wherein X is oxygen, nitrogen, a nitrogen atom with alkyl, a sulfur atom, a carbon atom and-SO2-; n is 1 or 2; r1 and R2 are each independently selected from-(CH2) m-; m is 0, 1, 2 or-(CH2) y-CO-; and y is 0, 1 or 2. On the basis of maintaining the pharmacological skeleton of the etixetecan, a series of derivations are performed on the etixetecan to form a series of etixetecan derivatives, and the compounds have the characteristics of high anti-tumor activity, low toxic and side effects and easiness in water dissolution, and have potential application value as anti-tumor single drugs or antibody coupling drugs. # imgabs0 #

The application provides methods of treating a tumor or cancer in a subject using antibody-toxin conjugates having the structure shown in General Formula (I), wherein Ab is conjugated to a camptothecin derivative through a linker. Ab refers to a bispecific antibody that simultaneously targets two different epitopes or targets. In one embodiment, Ab is a bispecific antibody having binding affinity to EGFR and HER3.

The invention relates to a preparation method of a camptothecin derivative and an intermediate thereof. The preparation method comprises the following steps: preparing a compound shown as a formula (V) from a compound shown as a formula (VI), and preparing the compound shown as the formula (IV) or the salt thereof from the compound shown as the formula (V). The method is high in yield, mild in reaction condition and suitable for industrial production. # imgabs0 #

The invention relates to application of a topoisomerase inhibitor and a conjugate thereof. Specifically, the inventor provides a class of camptothecin derivatives, linker conjugates and antibody-drug conjugates with novel structures, and the camptothecin derivatives, linker conjugates and antibody-drug conjugates have excellent anti-tumor activity and good lipophilicity. In-vitro and in-vivo experiments show that the drug conjugate containing the camptothecin derivative disclosed by the invention has an improved anti-tumor curative effect and high safety, and has an application prospect in the field of cancer treatment.

The present invention relates to an antibody-drug conjugate represented by formula (I) having an oxacycloalkyl-substituted camptothecin derivative as a drug toxic moiety, wherein the definitions of each group in the formula are as described in the specification, and the antibody-drug conjugate has a significant antitumor effect. [Formula 1] JPEG2026502963000098.jpg54170

This invention relates to compounds and methods for treating cancer. In various embodiments, the compound includes a heptamethine carbocyanine dye (HMCD) component, a camptothecin derivative component, and a linker moiety (L) connecting the HMCD component and the camptothecin derivative component. In various embodiments, the method includes administering a therapeutically effective amount of the compound to a subject, thereby contacting a tissue of the subject with the compound such that the compound binds to the tissue; detecting the compound bound to the tissue, wherein the presence of the compound bound to the tissue is indicative of the cancer in the subject; and delivering the compound to the tissue thereby treating the cancer in the subject.

The invention relates to preparation of a novel indole camptothecin derivative and an application of the novel indole camptothecin derivative in an anti-tumor aspect. The structural general formula of the compound is shown in the specification. In-vitro cytotoxic activity screening results show that the novel indole camptothecin derivative has broad-spectrum antitumor activity, and shows relatively strong inhibitory activity on human liver cancer cells (HepG2), human non-small cell lung cancer cells (A549), human colon cancer cells (SW480), human intrahepatic bile duct cancer cells (RBE), human breast cancer cells (MCF-7), human pancreatic cancer cells (BxPC3), human bladder cancer cells (T24) and human bladder cancer cells (umuc3). Wherein the anti-tumor activity of the compound D-18 is the most prominent, the compound D-18 shows a relatively strong inhibition effect on the tested 8 tumor cell lines, the IC50 range is 0.2585-10.69 mu M, the compound D-18 is obviously superior to that of a contrast drug irinotecan, and the activity of the compound D-18 is equivalent to that of topotecan. Therefore, the indole camptothecin derivative is expected to be developed into a novel antitumor drug. # imgabs0 #

Disclosed are new anti-HER2 ADCs conjugated to camptothecin derivatives as toxins for therapeutic use. The antitumor effects of the ADCs of Formula (PL-A) (e.g., compounds MB-2a and MB-3a (trastuzumab meditecan)) render these compounds useful for treating cell proliferative diseases such as cancers.

Disclosed are new anti-HER2 ADCs conjugated to camptothecin derivatives as toxins for therapeutic use. The antitumor effects of the ADCs of Formula (PL-A) (e.g., compounds MB-2a and MB-3a (trastuzumab meditecan)) render these compounds useful for treating cell proliferative diseases such as cancers.

The present invention provides a novel camptothecin derivative compound, a pharmaceutically acceptable salt, a stereoisomer, or a prodrug thereof, and a method for preparing same and use thereof. The compound has a structure represented by formula (I) and has good anticancer activity.

Provided is a novel camptothecin derivative or a conjugate thereof, and a preparation method therefor and an application thereof in medicine. Specifically, provided is a compound represented by general formula (A) or a ligand-drug conjugate thereof, a preparation method therefor, and an application of the ligand-drug conjugate and a pharmaceutical composition thereof in the preparation of a drug for the treatment of cancer or immunological diseases.

This invention belongs to the field of pharmaceutical compound technology, and discloses a camptothecin derivative, its preparation method, and its application. The preparation method of the camptothecin derivative includes the following reaction steps: adding camptothecin, isovaleraldehyde / n-butyraldehyde, and Mes-Acr to dichloromethane. + TPA and TFA are mixed under inert gas protection and undergo a Minisci reaction. The product after the reaction is separated and purified to obtain a camptothecin derivative. In summary, a novel camptothecin derivative is provided, and the preparation method is simple. In addition, the novel camptothecin derivative based on this invention can inhibit tumor cell growth and serves as a potential anticancer drug. Specifically, its inhibitory activity against HepG2 liver cancer cells is superior to CPT and SN-38, and its inhibitory activity against MCF-7 breast cancer cells is superior to SN-38.

The present invention relates to a camptothecin derivative represented by Formula I, a pharmaceutical composition, and a method for preparing and using the same. The camptothecin derivative has good tumor-inhibiting activity and can be used to treat or prevent tumors and to prepare medicines for treating or preventing neoplastic diseases. [Formula 1] JPEG2025541854000098.jpg49169

The invention relates to the field of biological medicines, and particularly discloses a camptothecin derivative as well as a preparation method and application thereof. The structural general formula of the camptothecin derivative is # imgabs0, wherein the structural general formula of R is # imgabs1 # R1 is selected from one of CH3, (CH2) 4CH3, citronellol and piperonol; x is selected from one of S, S-S, Se, O, C and C-C; and n is 1 or 2. The camptothecin derivative disclosed by the invention has good in-vitro anti-tumor activity, and the problem that the application of the camptothecin body serving as an anti-cancer drug is limited due to relatively high toxicity is solved.

The present invention relates to: an active camptothecin derivative (a) represented by Formula 1 designed so as to bind to a DDX5 protein and an E3 ligase; a prodrug (b) thereof, preferably an antibody-drug conjugate (ADC) thereof, designed so as to release the active camptothecin derivative (a) at a target site in vivo; the active camptothecin derivative (a) or the FL118 compound shown in the formula 2 is connected with a complex (c) containing a target DDX5 protein ligand through a joint, so that the 1-type topoisomerase inhibition capability in the active camptothecin derivative (a) or the FL118 compound shown in the formula 2 is inactivated. The active camptothecin derivative designed according to the present invention can bind to DDX5 protein in cells and induce cell death by degradation of the DDX5 protein.

The invention relates to a preparation technology of a camptothecin derivative targeted long-acting liposome. Firstly, a long-acting liposome with a targeting function is prepared, folic acid is modified on the surface of the liposome to realize an active targeting function, a metal copper ion and triethanolamine system is used for increasing the drug loading ratio of the liposome, and then the drug loading ratio and the photo-thermal performance of the camptothecin derivative are enhanced by utilizing the pi-pi conjugation effect of the camptothecin derivative and indocyanine green. The long-acting liposome prepared by the invention is uniform in particle size distribution and good in dispersity, can effectively protect a camptothecin lactone ring from being hydrolyzed and inactivated, prolongs the half-life period and stability of a medicine, and effectively solves the problems of poor water solubility, high toxicity, low bioavailability and the like of camptothecin. The prepared targeted long-acting liposome has a targeting property on folate receptor overexpressed tumor cells, further improves the anti-tumor effect of the drug, reduces the toxic and side effects on normal cells, can be applied to targeted therapy of the anti-tumor drug, and has a good application prospect.

Provided are a polypeptide-coupled drug and an anti-tumour use thereof. The polypeptide-coupled drug is a compound of formula (I) or a pharmaceutically acceptable salt thereof. In formula (I), P is a cyclic peptide containing 4-9 amino acids, L is a linking group, and D is selected from topoisomerase I inhibitors; the polypeptide-coupled drug has better tumour growth inhibitory activity. P-L-D (I)

The invention discloses a novel camptothecin compound or a stereoisomer or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the camptothecin compound or the stereoisomer or the pharmaceutically acceptable salt, and application of the camptothecin compound or the stereoisomer or the pharmaceutically acceptable salt as an antitumor drug. According to the structure, R1, R2 and R3 are independently selected from hydrogen, deuterium, halogen, hydroxyl, cyano, sulfydryl, sulfuryl, sulfoxide, nitro, substituted or unsubstituted amido, carboxyl, acylamino, deuterated alkyl, C1-6 alkyl, C1-6 alkoxy, C1-6 halogenated alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C3-6 heterocyclic radical, aryl or heteroaryl; or R1 and R2 as well as R2 and R3 are respectively connected with adjacent carbon atoms to form 5-7-membered cycloalkyl or heterocycloalkyl; the 5-to 7-membered cycloalkyl or heterocyclic cycloalkyl is optionally substituted by one or more halogens or deuterium atoms, alkyl and alkoxy. The compound has a good anti-tumor effect.

This invention provides an irinotecan-conjugated polypeptide compound, its preparation method, and its application, belonging to the field of biomedical technology. Irinotecan (Dxd) is the active pharmaceutical ingredient. Irinotecan belongs to the topoisomerase I inhibitor class—camptothecin derivatives—and is a semi-synthetic small molecule chemotherapeutic drug capable of directly killing cancer cells in the active division phase and inhibiting tumor growth. TYLCTACDYTHH is a highly effective PDPN-targeting peptide that can effectively target the PDPN site in human glioblastoma. In vitro and in vivo experimental results show that the conjugated compound of this invention can significantly inhibit the proliferation of primary glioblastoma cells and effectively inhibit the growth of intracranial orthotopic xenografts in NOD-SCID mice, demonstrating good anti-tumor activity. This compound shows promise for targeted therapy of glioblastoma and has the potential to prolong patient survival.

The anti-cancer use of a camptothecin derivative which demonstrates a surprising resistance to the degrading effects of Human Serum Albumin ("HSA") in vivo is disclosed. Since HSA represents about half of serum protein in human blood, previous camptothecins generally worked poorly or not at all in vivo due to inactivation by HSA among other factors. Since NSS-01 is similar in mechanism of action to other camptothecins, and as demonstrated herein has both: (i) greater anti-tumor activity against various human cancers and (ii) less toxicity at therapeutic dosing - than topotecan and irinotecan; and without wishing to be bound by theory, NSS-01 demonstrated desirable antitumor activity against adenocarcinomas, it therefore should demonstrate desirable antitumor activity against other cancers that are susceptible to Topoisomerase I inhibitors.

Provided are a C9-substituted camptothecin derivative and a conjugate thereof. Specifically disclosed is a compound represented by formula (I) or a pharmaceutically acceptable salt thereof. The camptothecin derivative and the conjugate thereof have a good cell killing effect.

The invention provides a novel antibody drug conjugate based on camptothecin derivatives. The antibody drug conjugate has a structure as shown in the specification. The antibody drug conjugate shows higher spectator killing activity and higher tumor growth inhibiting activity, meanwhile, the killing effect on positive cells is weaker, and higher effectiveness and safety are achieved. # imgabs0 #

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

The invention relates to a topoisomerase inhibitor as well as a conjugate and application thereof. Specifically, the invention discloses a camptothecin derivative with a brand new structure, a linker conjugate and an antibody-drug conjugate. Experimental results show that by using the camptothecin derivative with high lipophilicity, the anti-tumor effect of the ADC drug can be remarkably improved, so that linker conjugates and cytotoxic small molecules are expected to be applied to the field of biological medicines.