Boron carrying agent for integrated tumor diagnosis and treatment, and preparation method therefor and use thereof

Patent metadata

Field	Value
Publication number	US-12570674-B2
Application number	US-202117908630-A
Country	US
Kind code	B2
Filing date	Mar 1, 2021
Priority date	Mar 3, 2020
Publication date	Mar 10, 2026
Grant date	Mar 10, 2026

Abstract

The present invention relates to a boron carrying agent for integrated tumor diagnosis and treatment, and a preparation method therefor and use thereof. Provided is a compound represented by formula I: wherein an R group is hydrogen or alkyl. A boron atom connected to the benzene ring may be 10B or natural boron, and at least one fluorine atom in —BF 3- is radiolabeled. The present invention generally relates to the fields of radiopharmaceuticals and nuclear medicine. The compound in the present invention can be used for a drug for integrated diagnosis and treatment in tumor diagnosis and BNCT treatment, and by means of the same chemical structure, a reliable distribution result of a drug in vivo is provided.

First claim

What is claimed:

1 . A compound of Formula I:

wherein, R group is hydrogen, alkyl, or methyl.

2 . The compound according to claim 1 , wherein:
the boron atom attached to the benzene ring is 10 B or natural boron, at least one of the fluorine atoms in —BF 3 − is radiolabeled; and the boron atom in —BF 3 − is natural boron.

3 . A composition of a boron-carrying agent comprising the compound according to claim 1 and a pharmaceutically acceptable carrier.

4 . The composition of the boron-carrying agent according to claim 3 , further comprising a component selected from the group consisting of fructose, disodium mercaptoundecahydrododecaborate and dimers thereof, boronated dendrimer-EGF bioconjugates, EGFR monoclonal antibody-borate conjugates, FR-targeted boron-containing liposomes, FR-targeted boron-containing nanoparticles, and borate porphyrins.

5 . A method of preparing the compound according to claim 1 the method, comprising steps of:
producing an intermediate containing double boron trifluoride groups

by adding KHF 2 solution to compound 7

and adding hydrochloric acid to reach an acidity of pH<0; and
increasing the acidity to a pH of 1.5 to 4 to obtain the compound according to claim 1 .

6 . The method according to claim 5 , wherein compound 7 is obtained by:
adding NaOH solution to compound 6

to achieve a final concentration of 0.4-0.6 M,
stirring the solution at room temperature for 20-40 minutes, and
adding concentrated hydrochloric acid for neutralization.

7 . The method according to claim 5 , further comprising obtaining compound 3

by adding N-methyliminoacetic acid to compound 2

8 . The method according to claim 5 , further comprising:

(1) converting p-bromobenzene ethanol

to compound 2
(2) converting compound 2 to compound 3

with the addition of N-methyliminoacetic acid;
(3) converting compound 3 to compound 4

(4) converting compound 4 to compound 5

(5) converting compound 5 to compound 6

(6) converting compound 7 to compound 8

and
(7) converting compound 8 to

9 . A method of treating or diagnosing cancer using the boron-carrying compound according to claim 1 .

10 . The method according to claim 9 , wherein the medicament is a boron-carrying agent for integrated tumor diagnosis and treatment or boron neutron capture therapy.

11 . The method according to claim 9 , wherein the cancer is at least one of squamous cell carcinoma, lung cancer, peritoneal cancer, hepatocellular carcinoma, gastric cancer, pancreatic cancer, melanoma, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatic tumor, breast cancer, colon cancer, colorectal cancer, uterine cancer, salivary gland cancer, kidney cancer, prostate cancer, vulvar cancer, thyroid cancer, head and neck cancer, B-cell lymphoma, or leukemia.

12 . A method of treating or diagnosing cancer using the boron-carrying agent according to claim 3 .

13 . The method according to claim 12 , wherein the boron-carrying agent is for integrated tumor diagnosis and treatment or boron neutron capture therapy.

14 . The method according to claim 12 , wherein the cancer is at least one of squamous cell carcinoma, lung cancer, peritoneal cancer, hepatocellular carcinoma, gastric cancer, pancreatic cancer, melanoma, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatic tumor, breast cancer, colon cancer, colorectal cancer, uterine cancer, salivary gland cancer, kidney cancer, prostate cancer, vulvar cancer, thyroid cancer, head and neck cancer, B-cell lymphoma, or leukemia.

Assignees

• Univ Beijing

Inventors

• Liu Zhibo
• Chen Junyi

Classifications

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title

• A61K51/04

  Organic compounds · CPC title

• A61K41/0095

  Boron neutron capture therapy, i.e. BNCT, e.g. using boronated porphyrins · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K41/00

  Medicinal preparations obtained by treating materials with wave energy or particle radiation {; Therapies using these preparations} · CPC title