Photosensitizer and derivatives and application thereof

Patent metadata

Field	Value
Publication number	US-11504428-B2
Application number	US-201716633087-A
Country	US
Kind code	B2
Filing date	Nov 24, 2017
Priority date	Aug 4, 2017
Publication date	Nov 22, 2022
Grant date	Nov 22, 2022

Abstract

A photosensitizer and derivative, application thereof. The photosensitizer has the structure of general formula I, wherein X is S or Se, Y is organic or inorganic ion, R 1 and R 2 are independently selected from H, alkyl, alkoxy, alkyl amido, alkyl azide and the like; R 3 is selected from H, alkyl, alkoxy, amino sulfonyl, hydroxyl, carboxyl and the like, and L 1 is a linker selected from —(CH 2 ) n1 — or —(CH 2 CH 2 O) n2 —. The derivatives are molecular medicines with drug molecules of anticancer and chemotherapy or tumor targeting function connected to the said photosensitizer. The photosensitizer has excellent near infrared characteristics and low dark toxicity and is used in the field of photodynamic tumor therapy. The introduction of benzophenothiazine or benzophenoselenazine into derivatives with tumor-targeting function could improve the specific uptake of photosensitizer in tumor tissues. Moreover, clinical anticancer drugs can be introduced into the structure of benzophenothiazine or benzophenoselenazine to achieve the purpose of combining therapy of photodynamic therapy and chemotherapy.

First claim

The invention claimed is:

1. A photosensitizer of formula I:

wherein:
X is Se;
Y is selected from halogen ion, ClO 4 − , PF 6 − , BF 4 − , CH 3 COO − , and OTs − ;
R 1 and R 2 are independently selected from H, alkyl, alkoxy, alkylamido, alkyl azide, alkylalkynyl, alkylamino, alkylsulfonyl, alkylhydroxy, and alkylcarboxy;
R 3 is selected from H, alkyl, alkoxy, aryloxy, morpholinyl, carbonyl, amido, azido, alkynyl, amino, sulfonic acid, hydroxy and carboxy; and
L 1 is a linking chain selected from —(CH 2 ) m — and —(CH 2 CH 2 O) n —,
m being an integer from 5 to 20, and n being an integer from 2 to 20.

2. The photosensitizer of claim 1 , wherein R 1 and R 2 are independently selected from H, alkyl group of C 1-5 , alkoxy group of C 1-5 , alkyl alkyne group of C 2-5 , alkyl sulfonyl group of C 2-6 , and alkyl azide group of C 2-6 .

3. The photosensitizer of claim 1 , wherein the said R 3 is selected from amino, carboxyl, hydroxyl, and azido.

4. The photosensitizer of claim 1 , wherein m or n are independently 5, 6, 7 or 8.

5. The photosensitizer of claim 1 , wherein the said photosensitizer of formula I is

6. A method of treating tumor comprising administering an effective amount of a composition to a subject in need thereof, wherein the composition comprises the photosensitizer of claim 1 ; and subjecting the composition to light irradiation.

7. A derivative of the photosensitizer of claim 1 , having a formula of Formula II:

wherein X, Y, R 1 , R 2 , R 3 , and L 1 are as defined in claim 1 , and R 4 is an anticancer and chemotherapy drug molecule or a molecular drug with tumor targeting function.

8. The photosensitizer derivative of claim 7 , wherein R 4 is selected from a1 to a10:

9. The photosensitizer derivative of claim 7 is

10. A method of treating tumor comprising administering an effective amount of a composition to a subject in need thereof, wherein the composition comprises the photosensitizer derivatives of claim 7 ; and subjecting the composition to light irradiation.

Assignees

• Univ Dalian Tech
• Dalian Chromas Bioscience Co Ltd
• Dalian Chromas Biosctence Co Ltd

Inventors

• Peng Xiaojun
• Li Mingle
• Fan Jiangli
• Yao Qichao
• Du Jianjun
• Long Saran
• Wang Jingyun

Classifications

• C07D417/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K31/405

  Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• C07D495/04

  Ortho-condensed systems · CPC title

• C07D293/10

  condensed with carbocyclic rings or ring systems · CPC title