2-(1-n-hexyloxy)ethylchlorin f salt, and pharmaceutical composition and application thereof

A technology of ethyl chlorin and n-hexyloxy, which is applied in the direction of drug combination, pharmaceutical formula, antineoplastic drugs, etc., can solve the problems of increasing the production cost of photosensitizers, and achieve short retention time, strong photodynamic activity, dark less toxic effect

A technology of ethyl chlorin and n-hexyloxy, which is applied in the direction of drug combination, pharmaceutical formula, antineoplastic drugs, etc., can solve the problems of increasing the production cost of photosensitizers, and achieve short retention time, strong photodynamic activity, dark less toxic effect

CN104292235AActive Publication Date: 2015-01-21RAINBOW PHARMATECH
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  • 2-(1-n-hexyloxy)ethylchlorin f salt, and pharmaceutical composition and application thereof
  • 2-(1-n-hexyloxy)ethylchlorin f salt, and pharmaceutical composition and application thereof
  • 2-(1-n-hexyloxy)ethylchlorin f salt, and pharmaceutical composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Embodiment 1: Preparation of 2-(1-hexyloxy)ethyl chlorin f sodium salt (HPS)

[0058] step 1.The preparation of the chlorin f of formula 2

[0059]

[0060] Dissolve 660mg of pheophorbide a methyl ester of formula 1 in pyridine (4ml), add 25% KOH-MeOH solution (50ml), and pass O at 0°C 2 reacted for 1 hour, and then introduced N 2 20 minutes, quickly boil and reflux for 40 minutes, cool slightly, add water (200ml), and use 10% H 2 SO 4 Neutralize to pH 5-6, filter with suction, and after the filter cake is dried, go through silica gel column chromatography (chloroform:methanol=20:1), separate and obtain the chlorin f of formula 2 (black powder, 70mg, yield 12%) .

[0061] Compound of formula 2: UV-vis[CH 3 OH,λ max (nm)(ε)]:662(121104),498(41964),398(436694); 1 H NMR (400MHz, DMSO-d 6 )δ:9.88(1H,s,β-H),9.85(1H,s,γ-H),9.74(1H,s,α-H),9.05(1H,s,δ-H),8.33(1H ,dd,J=18.0,11.6Hz,2a-H),6.45(1H,d,J=18.0Hz,2b-H B ),6.21(1H,d,J=12.0Hz,2b-H A ),4.63(1H,m,8-H),4.47...

Embodiment 2

[0071] Embodiment 2: Preparation of 2-(1-hexyloxy)ethyl chlorin potassium salt (HPK)

[0072] 2-(1-hexyloxy)ethyl chlorin potassium salt (HPK) was prepared in a similar manner to Example 1, except that in step 3, the isopropanol solution of potassium hydroxide was used to replace Sodium hydroxide solution in isopropanol.

[0073] HR-ESI-MS m / z718.00945 gives quasi-molecular ion peak [M+H] + , corresponding to the formula C 38 h 47 N 4 o 5 K 2 (calculated value 718.00833), with an unsaturation of 16.5.

[0074]

Embodiment 3

[0075] Example 3: Activity of Compounds of the Invention as Photosensitizers

[0076] The resuscitated mouse sarcoma S180 cells were inoculated into the peritoneal cavity of female Kunming mice. After 2-3 generations of passage, when the number of viable cells reached more than 90% (tested by trypan blue), they were collected from the peritoneal cavity of mice under sterile conditions. Extract the milky white tumor fluid, add normal saline, and dilute to a cell density of about 1×10 7 Tumor cell suspension, set aside.

[0077] Another 30 female Kunming mice were taken, and 0.2ml of tumor cell suspension was inoculated subcutaneously on the right shoulder blade of each mouse. 6 mice in each group were randomly divided into 5 groups, and 48 hours after inoculation, the mice were administered separately from the tail vein of each group.

[0078] Blank control group (normal saline);

[0079] Positive control group (HPPH0.3mg / kg);

[0080] High dose group (HPS0.32mg / kg);

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Abstract

The invention relates to a 2-(1-n-hexyloxy)ethylchlorin f salt, and a pharmaceutical composition and an application thereof. Specifically, the invention relates to the 2-(1-n-hexyloxy)ethylchlorin f salt used in photo-dynamic therapy and / or sono-dynamic therapy. The salt is soluble in water, and has stable properties. The salt can be used as a photosensitizer and / or a sound-sensitizer. The salt is suitable to be used for treating and diagnosing relatively large malignant, precancerous lesions or benign lesions. The invention also relates to a pharmaceutical composition comprising the novel compound, and the application and a preparation method of the novel compound.

Description

technical field [0001] The present invention relates to novel compounds for use in Photodynamic therapy (PDT) and / or Sonodynamic therapy (SDT). Specifically, the present invention relates to 2-(1-n-hexyloxy)ethyl chlorin f salt, which is soluble in water, stable in properties, can be used as a photosensitizer and / or sound sensitizer, and is suitable for treating and diagnosis of larger malignant tumors as well as precancerous or benign lesions. The present invention also relates to pharmaceutical compositions comprising the novel compounds, uses and preparation methods of the novel compounds. Background technique [0002] In recent years, cancer has become one of the major diseases that seriously threaten human health. It is reported that cancer has become the first cause of death among Chinese patients, and one out of every four Chinese people who died died of cancer. The incidence of cancer is increasing at an average annual rate of 3%-5%. Due to the serious side effect...

Claims

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Application Information

Patent Timeline
21 Jan 2015
Publication
CN104292235A
IPC
C07D487/22; A61K41/00; A61P35/00
CPC
A61K41/0033; A61K41/0071; C07D487/22
Inventors
方起程; 方薇