CN-121991155-A - Abiraterone boron carrying agent with prostate cancer targeting as well as preparation method and application thereof

Abstract

The present disclosure relates to an abiraterone boron carrying agent with prostate cancer targeting, a preparation method and an application thereof, wherein abiraterone borane compounds comprise abiraterone borane and abiraterone borane acetate. The embodiment introduces the borane group into the structure of abiraterone acetate and abiraterone acetate based on the targeting and safety of the abiraterone acetate and the prostate cancer, so as to obtain a novel boron carrying agent for BNCT treatment of the prostate cancer. The novel boron carrying agent not only maintains the CYP17 enzyme inhibition activity of abiraterone and abiraterone acetate, but also provides the possibility of targeting prostate cancer cells for BNCT through the introduction of 10 B isotopes. Through the innovative drug design, the curative effect and the selectivity of BNCT in the treatment of the prostate cancer can be remarkably improved, the damage to normal tissues is reduced, and a safer and more effective treatment option is provided for the prostate cancer patients.

Inventors

• Zhan miao
• WANG NAN

Assignees

• 西北工业大学
• 西北工业大学深圳研究院

Dates

Publication Date

20260508

Application Date

20251224

Claims (7)

1. 1. The abiraterone borane compound is characterized in that the abiraterone borane compound is abiraterone borane or abiraterone Long Peng alkyl acetate, and the chemical formulas of the abiraterone borane and the abiraterone borane acetate are as follows respectively: 、 。
2. 2. The process for the preparation of abiraterone borane compounds as claimed in claim 1, comprising the steps of: S1, sequentially adding sodium borohydride and sodium bicarbonate into anhydrous tetrahydrofuran, then adding abiraterone or abiraterone acetate, and then stirring; s2, adding the THF/H 2 O mixed solution under the protection of nitrogen, and then stirring; s3, after the reaction is finished, extracting, washing, filtering and removing the solvent to obtain an Abiraterone borane or Abiraterone borane acetate crude product; s4, purifying the crude product to obtain abiraterone borane or abiraterone borane acetate.
3. 3. The preparation method of the abiraterone borane compound according to claim 2, wherein in S1, the reaction molar ratio of sodium borohydride, sodium bicarbonate, abiraterone or abiraterone acetate is 2:4:1.
4. 4. Use of an abiraterone borane compound according to claim 1 for the manufacture of a medicament for the treatment of prostate cancer.
5. 5. Use of an abiraterone borane compound according to claim 4 for the manufacture of a medicament for the treatment of prostate cancer, wherein the abiraterone borane compound is used as a prodrug of a medicament for the treatment of prostate cancer.
6. 6. Use of abiraterone boranes according to claim 4 for the manufacture of a medicament for the treatment of prostate cancer, wherein the treatment is boron neutron capture treatment.
7. 7. Use of an abiraterone boron carrier in the manufacture of a medicament for the treatment of prostate cancer, wherein the abiraterone Long Peng carrier comprises an abiraterone borane-like compound as defined in claim 1.

Description

Abiraterone boron carrying agent with prostate cancer targeting as well as preparation method and application thereof Technical Field The invention relates to the technical field of pharmaceutical chemistry, in particular to an abiraterone boron carrying agent with prostate cancer targeting, a preparation method and application thereof. Background Prostate cancer is one of the common malignant tumors that endanger the life of men, and androgen deprivation therapy has been the main therapeutic strategy in the field of prostate cancer treatment. However, as the disease progresses, some patients develop castration-resistant prostate cancer, in which stage the tumor cells no longer rely on androgen growth and androgen deprivation therapy is difficult to effect. In recent years, it has been found that a key enzyme involved in androgen synthesis, 17-alpha hydroxylase/C17, 20-lyase (CYP 17), is highly expressed in testis, adrenal gland and prostate tumor tissue, and its activity is closely related to androgen biosynthesis. Thus, by inhibiting the activity of CYP17 to block androgen synthesis, androgen levels can be reduced in vivo, thereby inhibiting the growth and proliferation of prostate cancer cells. Based on this mechanism, abiraterone has been widely studied and applied in clinical treatment as a CYP17 inhibitor. However, the short half-life of abiraterone, low bioavailability, and its chemical and pharmacokinetic properties limit its immediate use. Abiraterone acetate has been developed as a prodrug thereof in order to improve the stability and bioavailability of the drug. Abiraterone acetate can be quickly converted into an active metabolite Abiraterone in vivo, and plays a pharmacological role in inhibiting CYP 17. Clinical studies show that the combination of abiraterone acetate and corticosteroid can significantly prolong the survival time of metastatic castration resistant prostate cancer patients and improve the quality of life of the patients. Although abiraterone and abiraterone acetate are widely used clinically as first-line drugs, existing treatment schemes still have some limitations, and some patients have acquired drug resistance, and the mechanism is not clear, and may involve androgen receptor mutation and independent signaling pathway activation. Such as side effects of the drug, patient tolerance, compliance with long-term treatment, etc. Therefore, the development of novel CYP17 inhibitors and derivatives thereof, and the optimization of the formulation and the administration route of the drugs, have important scientific significance for improving the treatment effect of the prostate cancer and improving the prognosis of patients. In summary, the existing medicines have the defects in stability, safety, durability and convenience, and the optimization is needed. Accordingly, there is a need to improve one or more problems in the related art as described above. It is noted that this section is intended to provide a background or context for the technical solutions of the present disclosure as set forth in the claims. The description herein is not admitted to be prior art by inclusion in this section. Disclosure of Invention The present invention is directed to a class of abiraterone boron carriers with prostate cancer targeting, and a preparation method and application thereof, and further, to at least some extent, overcome one or more of the problems due to the limitations and disadvantages of the related art. The invention firstly provides an abiraterone borane compound which is abiraterone borane or abiraterone Long Peng acetate, wherein the chemical formulas of the abiraterone borane and the abiraterone borane acetate are as follows: 、。 The invention further provides a preparation method of the Abiraterone borane compound, which comprises the following steps: S1, sequentially adding sodium borohydride and sodium bicarbonate into anhydrous tetrahydrofuran, then adding abiraterone or abiraterone acetate, and then stirring; s2, adding the THF/H 2 O mixed solution under the protection of nitrogen, and then stirring; s3, after the reaction is finished, extracting, washing, filtering and removing the solvent to obtain an Abiraterone borane or Abiraterone borane acetate crude product; s4, purifying the crude product to obtain abiraterone borane or abiraterone borane acetate. In the invention, in S1, the reaction mole ratio of sodium borohydride, sodium bicarbonate, abiraterone or abiraterone acetate is 2:4:1. The invention also provides application of the abiraterone borane compound in preparation of a medicament for treating prostate cancer. In the invention, the abiraterone borane compounds are used as prodrugs of medicaments for treating prostate cancer. In the present invention, the treatment is boron neutron capture treatment. The invention also provides application of the Abiraterone Long Peng carrying agent in preparing a medicament for treating prostate cancer, wherein the Abiraterone