Peptoid, and its preparation method and use

Patent metadata

Field	Value
Publication number	US-11370813-B2
Application number	US-201916642572-A
Country	US
Kind code	B2
Filing date	Oct 10, 2019
Priority date	Jan 3, 2019
Publication date	Jun 28, 2022
Grant date	Jun 28, 2022

Abstract

The embodiments disclosed herein provide a peptoid, which is a compound of Formula I or a stereoisomer, a mixture of stereoisomers, or a pharmaceutically acceptable salt thereof. N—R 4 , N—R 3 , N—R 2 , and N—R 1 in Formula I are

respectively. The peptoid has a strong binding ability with EGFR protein. It can be used not only for targeted treatment of diseases associated with EGFR protein, but also for imaging detection or prognosis monitoring of diseases associated with EGFR protein.

First claim

What is claimed is:

1. A peptoid, which is a compound of Formula I, or a stereoisomer, a mixture of stereoisomers, or a pharmaceutically acceptable salt thereof,

wherein N—R 4 , N—R 3 , N—R 2 , and N—R 1 in Formula I are

respectively.

2. The peptoid according to claim 1 , wherein the pharmaceutically acceptable salt is hydrochloride, hydrobromide, sulfate, nitrate, phosphate, formate, acetate, propionate, fumarate, glycolate, pyruvate, malate, malonate, benzoate, cinnamate, mandelate, salicylate, maleate, citrate, succinate, tartrate, mesylate, ethanesulfonate, or p-toluenesulfonate.

3. The peptoid according to claim 1 , which is the compound of Formula I.

4. A pharmaceutical composition comprising:
the peptoid according to claim 1 ; and
a pharmaceutically acceptable adjuvant.

5. The pharmaceutical composition according to claim 4 , wherein the pharmaceutically acceptable adjuvant is any one or more of excipients, diluents, carriers, flavoring agents, binders, and fillers.

6. A pharmaceutical composition comprising:
the peptoid according to claim 2 ; and
a pharmaceutically acceptable adjuvant.

7. A pharmaceutical composition comprising:
the peptoid according to claim 3 ; and
a pharmaceutically acceptable adjuvant.

8. A method for imaging detection or prognostic monitoring of a cancer associated with EGFR protein, comprising administering the pharmaceutical composition according to claim 4 , labeled with flurorphore.

9. The method according to claim 8 , wherein the disease associated with EGFR protein is breast cancer, kidney cancer, colon cancer, rectal cancer, lung cancer, ovarian cancer, head and neck cancer, bladder cancer, pancreatic cancer, or glioma.

10. The method according to claim 9 , wherein the disease associated with EGFR protein is non-small cell lung cancer.

11. A method for preparing the peptoid according to claim 1 , comprising:
(1) carrying out an amidation reaction between a compound of Formula II and an amino group at a terminal end of a solid phase support resin to form an amide bond;

wherein R is OH or Cl;
(2) adding a monomer to replace the bromine atom through a nucleophilic substitution reaction;
(3) repeating steps (1) and (2) until the synthesis of all subunits is completed,
wherein the monomers are added in an order of cysteine, monoprotected tetramethylenediamine, monoprotected tetramethylenediamine, allylamine, 2-aminomethylfuran, α-methylbenzylamine, and 3,4-methylenedioxybenzylamine, wherein the wording “monoprotected” means that one amino group in the diamine is protected by an amino protecting group; and
(4) removing the amino protecting group on the side chain, and cleaving the peptoid from the resin.

12. The method according to claim 11 , wherein the α-methylbenzylamine used is R(+)-α-methylbenzylamine.

13. A chip comprising the peptoid according to claim 1 .

14. The chip according to claim 13 , wherein the peptoid is coupled to a surface of the chip.

15. The chip according to claim 13 , wherein the chip is a microfluidic chip.

16. A kit for identifying circulating tumor cells, comprising: a box body, and the chip according to claim 15 disposed in the box body.

17. A method for detecting circulating tumor cells, comprising contacting the chip of claim 13 with a biological sample.

Assignees

• Beijing Boe Technology Dev Co Ltd
• Boe Technology Group Co Ltd

Inventors

• Zhao Zijian

Classifications

• G01N33/575

  for cancer · CPC title

• B01L3/5027

  by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip · CPC title

• C40B40/10

  Libraries containing peptides or polypeptides, or derivatives thereof · CPC title

• C07K1/04

  on carriers {(C07K1/003, C07K1/006 take precedence)} · CPC title

• C07K7/06 Primary

  having 5 to 11 amino acids · CPC title