Prostate-specific membrane antigen targeting compound with long circulation half-life period as well as preparation method and application thereof

A prostate-specific compound technology, applied in the field of nuclear medicine and molecular imaging, can solve the problems of insufficient combination of drugs and targets, inability to meet therapeutic purposes, low effective dose, etc., to enhance tumor uptake enrichment and retention time, prolong The effect of blood circulation half-life

Inactive Publication Date: 2021-06-22
YANTAI LANNACHENG BIOTECHNOLOGY CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, such metabolic characteristics are very unfavorable for radionuclide therapy, because rapid metabolism and elution lead to low effective dose at the tumor site and short retention time, requiring high dose or more frequent administration to meet treatment needs. Increased the possibility of adverse reactions, can not meet the needs of therapeutic use
Those of ordinary skill in the art know that if the small molecule drug circulates in blood vessels for too short a time or is quickly cleared by the body, the combination of the drug and the target will be insufficient.

Method used

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  • Prostate-specific membrane antigen targeting compound with long circulation half-life period as well as preparation method and application thereof
  • Prostate-specific membrane antigen targeting compound with long circulation half-life period as well as preparation method and application thereof
  • Prostate-specific membrane antigen targeting compound with long circulation half-life period as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] Embodiment 1: the preparation of formula (II-1) compound 10

[0069] Synthesis of Compound 2:

[0070] 4,4'-diamino-3,3'-dimethylbiphenyl (compound 11) (2.12g, 10.0mmol), di-tert-butyl dicarbonate (2.2g, 10.0mmol) and N,N-Diisopropylethylamine (1.3g, 10.0mmol) and 20mL of dichloromethane were stirred overnight at room temperature, and the completion of the reaction was monitored by HPLC (r.t. was 10.13 minutes). Column purification (petroleum ether / ethyl acetate=5:1) yielded compound 2 as a white solid with a yield of 59%.

[0071] Synthesis of compound 3:

[0072] In a 50mL flask, compound 2 (0.31g, 1.0mmol) and 4mL of acetonitrile were dropped into the reaction flask in an ice bath, and 1.5mL of 2M hydrochloric acid was added dropwise to the reaction flask, reacted for 15min, and sodium nitrite (0.068g, 1.0mmol) was added ) was dissolved in 2mL of water, added dropwise into the reaction bottle again, reacted for half an hour, and used as A liquid for later use. In...

Embodiment 2-6

[0090] The compound structure of embodiment 2-6 is as shown in formula (II-2) to formula (II-6), and their preparation method all can refer to embodiment 1, in formula (II-2) and formula (II-3) Preparation of COOH-PEG that will react with compound 6 4 -COOH is replaced by COOH-PEG 2 -COOH, malonic acid or other suitable compounds; in the preparation of formula (II-4) to formula (II-6), the Nα-Fmoc-Nε-Boc-L-lysine of compound 4 reaction is replaced by Boc glycine , while replacing PSMA-617 reacted with compound 7 with PSMA-617-(Fmoc)Lys-, the following corresponding structure is obtained:

[0091]

[0092] or

[0093]

Embodiment 7-30

[0095] With reference to the preparation method of Example 1-6, prepare the compound expressed by the following formula (I):

[0096]

[0097]

[0098]

[0099]

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Abstract

The invention provides a prostate-specific membrane antigen (PSMA) targeting compound with a long circulation half-life period. The structure of the prostate-specific membrane antigen (PSMA) targeting compound is represented by a formula (I), wherein R1 is a prostate specific membrane antigen targeting compound; -(X)n-(CH2)m-(Y)q-, wherein X and Y are independently selected from lysine, glutamic acid or a derivative structure containing lysine and glutamic acid, n is an integer from 0 to 12, m is an integer from 0 to 60, q is an integer from 0 to 12, and each CH2 can be replaced by -O-, -NH(CO)- or -(CO)-NH- alone; L2 is -(CH2)p-, wherein p is an integer from 0 to 30, each CH2 can be substituted individually with -O-, -NH(CO)- or -(CO)-NH-; and R2 is a nuclide chelating group. The invention further provides a radioactive marker based on the structure of the compound; the compound and the radioactive marker have remarkably prolonged blood circulation half-life period and enhanced tumor uptake enrichment and retention time, and are suitable for nuclide treatment and imaging of PSMA high-expression tumors.

Description

technical field [0001] The invention relates to the fields of nuclear medicine and molecular imaging, in particular to a prostate-specific membrane antigen-targeting compound with a long circulation half-life and its preparation label and application. Background technique [0002] Prostate cancer is the second most common cancer in men worldwide and the sixth most common cancer in men in China. In the past ten years, the incidence of prostate cancer in China has risen rapidly, with an average annual growth rate of 12.07%. Elderly men are a high-risk group of prostate cancer, and the older the older the higher the probability of the disease. Prostate cancer is described as a "silent killer", and it is difficult to be detected in the early stage. About two-thirds of the patients have developed to the advanced stage when they are diagnosed. Data show that at least 65% to 75% of prostate cancer patients have bone metastases, bone pain, pathological fractures, limb movement dis...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K5/062C07K7/02C07K1/06C07K1/107C07K1/13A61K51/08A61K45/06A61P35/00
CPCC07K5/06026C07K7/02A61K51/08A61K45/06A61P35/00Y02P20/55C07K5/0812C07K5/0215C07K5/0202A61K51/0497A61K51/0402A61K51/04A61K51/088
Inventor 不公告发明人
Owner YANTAI LANNACHENG BIOTECHNOLOGY CO LTD
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