Unlock instant, AI-driven research and patent intelligence for your innovation.

A kind of docetaxel derivative activated by tumor microenvironment targeting and its application

A technology of tumor microenvironment and docetaxel, which is applied in the field of docetaxel derivatives and the preparation of antitumor drugs, can solve problems such as adverse reactions and side effects, and achieve good application prospects and reduced toxicity

Active Publication Date: 2017-09-15
上海亲合力生物医药科技股份有限公司
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the clinical application of this compound is limited because of its severe toxic and side effects and adverse reactions.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A kind of docetaxel derivative activated by tumor microenvironment targeting and its application
  • A kind of docetaxel derivative activated by tumor microenvironment targeting and its application
  • A kind of docetaxel derivative activated by tumor microenvironment targeting and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Example 1: Synthesis of docetaxel derivatives targeted for activation of tumor microenvironment.

[0050] The synthesis process includes the following steps:

[0051] Step 1: Synthesis of Cbz-L-Ala-L-Ala-OMe (Benzyloxycarbonyl-L-alanine-L-alanine methyl ester) (I).

[0052] Dissolve N-benzyloxycarbonyl-L-alanine (N-Cbz-L-Ala) (100g, 0.45mol) in N,N-dimethylformamide (3L), add 1-hydroxybenzene with stirring And triazole (72.6g, 0.54mol) and 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (103.3g, 0.54mol), stirred and reacted for 1 hour, ice Add L-alanine methyl ester (46.2g, 0.45mol) and N,N-diisopropylethylamine (173.8g, 1.34mol) N,N-dimethylformamide dropwise to the bath to 0℃ (1L) solution, after dripping, stir at room temperature for 10h, evaporate the solvent under reduced pressure, dissolve the crude product in dichloromethane (2L), wash with saturated ammonium chloride solution, water and saturated sodium chloride solution in turn, organic The phase was dr...

Embodiment 2

[0074] Example 2: The effect of the different groups of the compound in docetaxel activated by the tumor microenvironment on the drug formulation.

[0075] The different groups of the compound in docetaxel activated by the tumor microenvironment have a huge impact on the formulation of the drug. The synthesized S1, S2, S3 and S4 and various control compounds were vacuum dried, sterilized by gas, and then packed in a sterile room. Before animal experiments, S1, S2, S3 and S4 can be dissolved in solvent 1 (water for injection) or solvent 2 (45% alcohol, 55% water for injection) in a sterile room, and then diluted with water for injection to the desired concentration, and The comparative compounds (C1, C2, C3, C4, C5, C6) did not meet the requirements of the drug formulation, as shown in Table 2 below. Docetaxel is insoluble in water, and the solubility characteristics of docetaxel after modification have changed greatly, the solubility in water increased, and the changes in solubi...

Embodiment 3

[0085] Example 3: Method and content range for determination of the content of S1, S2, S3 and S4 in the obtained product.

[0086] Analytical HPLC (Agilent 1220 series), C8 column 5μm, 4.6mm ID×250mm, mobile phase 0-95% acetonitrile (ACN) was used for S1, S2, S3 and S4 in the obtained product. S1, S2 were measured , The purity of S3 and S4 are in the range of 95%-99%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a tumor microenvironment-targeted activated docetaxel derivative and its application. The tumor microenvironment-targeted activated docetaxel derivative has a structural formula: wherein R1 is Ala, Thr, Val or Ile R2 is any amino acid in Ala, Thr, Val or Asn; n selects any integer from 1 to 300. The docetaxel derivative activated by targeting the tumor microenvironment has the application of preparing antitumor drugs. The tumor microenvironment-targeted and activated docetaxel derivatives provided by the present invention have anti-tumor targeting properties, specific activation properties and immune-promoting properties, and the efficacy of inhibiting tumor growth and metastasis is greatly improved, and the drug The formulation changes, the toxicity is greatly reduced, and it has a very good application prospect.

Description

Technical field [0001] The present invention relates to an anti-tumor drug compound, in particular to a docetaxel derivative with targeted activation of tumor microenvironment and its use for preparing an anti-tumor drug. Background technique [0002] Docetaxel (the structural formula is: ) Is an effective anti-tumor agent widely used at present, mainly used for various solid tumors such as ovarian cancer and breast cancer, and also for lung cancer, colorectal cancer, melanoma, head and neck cancer, lymphoma, and brain tumors. Certain effect. However, the clinical application of this compound has severe side effects and adverse reactions, and its dosage is limited. Docetaxel can have bone marrow toxicity, causing neutropenia, neurotoxicity and cardiovascular toxicity. And can cause allergic reactions, overflow outside the blood vessels can cause local inflammation, hair loss, fatigue and liver toxicity. Therefore, there is a need to provide a targeted activating drug as an an...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07K5/083A61K31/337A61K47/64A61P35/00
Inventor 刘辰刘源
Owner 上海亲合力生物医药科技股份有限公司