102 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.

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 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.

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.

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.

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 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.

The invention relates to a camptothecin derivative and a conjugate thereof as well as a preparation method and medical application of the camptothecin derivative and the conjugate. The invention relates to a novel camptothecin compound derivative, a ligand drug conjugate containing the camptothecin compound derivative, a pharmaceutical composition containing the conjugate, and application of the conjugate in cancer treatment.

The invention provides a camptothecin derivative and an antibody-drug conjugate thereof. The compound is high in activity, small in toxicity and good in affinity, the direct targeted killing effect on tumor cells is achieved through the compound and an antibody drug conjugate, and the antibody drug conjugate containing the antibody is remarkable in cell killing effect and has the very high tumor inhibition rate.

The invention discloses a novel camptothecin derivative, a joint, a ligand-drug conjugate, a pharmaceutical composition containing the camptothecin derivative or conjugate, and corresponding medical application.

The invention relates to a camptothecin derivative as shown in a general formula I, a pharmaceutical composition as well as a preparation method and application of the camptothecin derivative. The camptothecin derivative has good tumor inhibition activity, and can be used for treating or preventing tumors and preparing medicines for treating or preventing tumor diseases.

The present invention discloses a camptothecin polypeptide nanoformulation with variable morphology, its preparation method and application. The camptothecin nanoformulation includes an amphiphilic polypeptide and a camptothecin derivative; the camptothecin derivative is covalently linked to the amphiphilic polypeptide through a disulfide bond. The camptothecin polypeptide nanoformulation has acid responsiveness and morphology transformability. Under normal physiological conditions, the nanoparticle structure is maintained to ensure its permeability at the tumor site; under the slightly acidic conditions of the tumor microenvironment, the morphology of the formulation changes from nanoparticles to nanofibers with a length of not less than 200 nm, which can improve the retention ability of camptothecin, increase its concentration at the tumor site, so as to reduce the administration concentration and achieve efficient killing of cancer cells; the camptothecin polypeptide nanoformulation has specificity, and the overexpressed GSH in cancer cells reduces the disulfide bond to release the original camptothecin drug, which can reduce the toxic side effects of camptothecin on normal cells in the blood circulation and achieve specific killing of cancer cells.

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.

In particular, antibody-drug conjugates (ADCs) that bind to the B7-H3 antigen are provided. Furthermore, pharmaceutical compositions and therapeutic methods for treating cancer using the ADCs provided herein are disclosed. This disclosure provides ADCs comprising an anti-B7-H3 antibody conjugated to a camptothecin derivative toxin or a duostatin derivative toxin via a linker moiety. In embodiments, the anti-B7-H3 antibody binds to B7-H3 expressing cancer cells, enabling selective uptake of the ADC into the cancer cells.

The present invention provides a class of camptothecin derivatives, compositions containing the same, and uses thereof. Specifically, the present invention provides a compound represented by formula (1) and a method for preparing the same, as well as the use of the compound represented by formula (1) and its optical isomers, crystal forms, and pharmaceutically acceptable salts in the preparation of a drug for treating cancer.

The invention discloses a camptothecin derivative as well as a preparation method and application thereof. The camptothecin derivative has a general formula shown as a structural formula (I). Wherein R1 is one of hydrogen, amino, hydroxyl, methyl, methoxyl, nitryl, halogen and trifluoromethyl, R2 is one of hydrogen, methyl, ethyl and halogen, and R3 is one of hydrogen and acetyl. The preparation method comprises the following steps: carrying out condensation reaction on (S)-4-ethyl-4-hydroxy-7, 8-dihydro-1H-pyran O [3, 4-F] indolizine-3, 6, 10 (4H)-ketone and an o-aminobenzaldehyde / acetophenone derivative in N, N-dimethylformamide under the protection of nitrogen, and synthesizing a target compound through the catalysis of trimethylchlorosilane. The camptothecin derivative prepared by the invention has a remarkable antifungal effect, and tests prove that the camptothecin derivative has broad-spectrum inhibitory activity on various plant pathogenic fungi. According to the invention, the resistance limitation of the traditional bactericide is broken through, and an efficient and low-toxicity novel solution is provided for prevention and treatment of fungal diseases of agricultural and forestry crops.