Amino-modified tetraphenylporphyrin compound as well as preparation method and application thereof

Abstract

The invention relates to an amino-modified tetraphenylporphyrin compound as well as a preparation method and application thereof. The compound has a structure (I) shown in the description, wherein R2 and R3 are positioned at an ortho-position (o-) or meta-position (m-) or para-position (p-) of a benzene ring. The invention relates to the fields of photosensitive medicaments (also known as photosensitizers or photodynamic medicaments) and photodynamic therapy, in particular to a porphyrin photosensitizer, a preparation method thereof and application of the porphyrin photosensitizer in the field of medicine. The photosensitive medicament disclosed by the invention has the advantages of stable chemical property, single component and very strong photodynamic activity, and can be applied to photodynamic therapy of diseases such as tumors, retinal macular degeneration, actinic keratosis, port wine stains and condyloma acuminata.

Description

technical field

[0001] The invention relates to the field of photosensitizing drugs and photodynamic therapy, in particular to a class of amino-modified tetraphenylporphyrin compounds and a preparation method and application thereof. Background technique

[0002] Photodynamic therapy (PDT) is a new method for the treatment of tumors, macular degeneration, actinic keratosis, port wine stains, genital warts and other diseases. Since entering clinical research in the 1970s, PDT has made remarkable achievements in clinical treatment because of its good selectivity, low toxicity, good reproducibility, safety, minimal invasiveness, synergy and Advantages such as relatively low cost stand out, showing huge potential and strong vitality.

[0003] The principle of photodynamic therapy is that after the photosensitizer enters the body, it selectively gathers in the target tissue along with the blood circulation, and then directly irradiates the tumor tissue with a laser of a certain ...

Examples

Embodiment 1

[0034] Preparation of 2-morpholine-5,10,15,20-tetrakis(4-chlorophenyl)porphyrin (photosensitizer 1):

[0035] In a 100mL three-necked flask, 2-nitro-5,10,15,20-tetrakis(4-chlorophenyl)porphyrin (183mg, 0.23mmol) was dissolved in N,N-dimethylformamide (20mL) , adding potassium carbonate (360mg, 2.56mmol) and morpholine (0.2mL), heated to reflux for about 3h, and monitored by TLC until the reaction was complete. The reaction solution was evaporated to dryness, and dichloromethane (150 mL) was added for extraction. The organic phase was washed with water (100 mL×3), washed with saturated brine (100 mL×3), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was subjected to column chromatography (eluent: petroleum ether:dichloromethane=10:1) to obtain a purple solid powder 2-morpholine-5,10,15,20-tetra( 111.4 mg of 4-chlorophenyl) porphyrin, the yield was 58%. 1 H NMR (400MHz, CDCl3): δ8.80-8.68(m, 5...

Embodiment 2

[0037] Preparation of 2-tetrahydropyrrole-5,10,15,20-tetrakis(4-chlorophenyl)porphyrin (photosensitizer 2):

[0038] In a 100mL three-necked flask, 2-nitro-5,10,15,20-tetrakis(4-chlorophenyl)porphyrin (183mg, 0.23mmol) was dissolved in N,N-dimethylformamide (20mL) , adding potassium carbonate (360mg, 2.56mmol) and tetrahydropyrrole (0.2mL), heated to reflux for about 3h, and monitored by TLC until the reaction was complete. The reaction solution was evaporated to dryness, and dichloromethane (150 mL) was added for extraction. The organic phase was washed with water (100 mL×3), washed with saturated brine (100 mL×3), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was subjected to column chromatography (eluent: petroleum ether:dichloromethane=3:1) to obtain a purple solid powder 2-tetrahydropyrrole-5,10,15,20-tetrahydropyrrole (4-Chlorophenyl)porphyrin 90.4 mg, yield 48%. 1 H NMR (400MHz, CDCl...

Embodiment 3

[0040] Preparation of 2-piperidine-5,10,15,20-tetrakis(4-chlorophenyl)porphyrin (photosensitizer 3):

[0041] In a 100mL three-necked flask, 2-nitro-5,10,15,20-tetrakis(4-chlorophenyl)porphyrin (183mg, 0.23mmol) was dissolved in N,N-dimethylformamide (20mL) , adding potassium carbonate (360mg, 2.56mmol) and piperidine (0.3mL), heated to reflux for about 3h, monitored by TLC until the reaction was complete. The reaction solution was evaporated to dryness, and dichloromethane (150 mL) was added for extraction. The organic phase was washed with water (100 mL×3), washed with saturated brine (100 mL×3), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was subjected to column chromatography (eluent: petroleum ether: dichloromethane = 3: 1) to obtain a purple solid powder 2-piperidine-5,10,15,20-tetra( 4-chlorophenyl) porphyrin 88.2 mg, yield 46%. 1 H NMR (400MHz, CDCl 3 ): δ8.83-8.81(m, 3H), 8.76-8...

technical field

[0001] The invention relates to the field of photosensitizing drugs and photodynamic therapy, in particular to a class of amino-modified tetraphenylporphyrin compounds and a preparation method and application thereof. Background technique

[0002] Photodynamic therapy (PDT) is a new method for the treatment of tumors, macular degeneration, actinic keratosis, port wine stains, genital warts and other diseases. Since entering clinical research in the 1970s, PDT has made remarkable achievements in clinical treatment because of its good selectivity, low toxicity, good reproducibility, safety, minimal invasiveness, synergy and Advantages such as relatively low cost stand out, showing huge potential and strong vitality.

[0003] The principle of photodynamic therapy is that after the photosensitizer enters the body, it selectively gathers in the target tissue along with the blood circulation, and then directly irradiates the tumor tissue with a laser of a certain ...

Examples

Embodiment 1

[0034] Preparation of 2-morpholine-5,10,15,20-tetrakis(4-chlorophenyl)porphyrin (photosensitizer 1):

[0035] In a 100mL three-necked flask, 2-nitro-5,10,15,20-tetrakis(4-chlorophenyl)porphyrin (183mg, 0.23mmol) was dissolved in N,N-dimethylformamide (20mL) , adding potassium carbonate (360mg, 2.56mmol) and morpholine (0.2mL), heated to reflux for about 3h, and monitored by TLC until the reaction was complete. The reaction solution was evaporated to dryness, and dichloromethane (150 mL) was added for extraction. The organic phase was washed with water (100 mL×3), washed with saturated brine (100 mL×3), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was subjected to column chromatography (eluent: petroleum ether:dichloromethane=10:1) to obtain a purple solid powder 2-morpholine-5,10,15,20-tetra( 111.4 mg of 4-chlorophenyl) porphyrin, the yield was 58%. 1 H NMR (400MHz, CDCl3): δ8.80-8.68(m, 5...

Embodiment 2

[0037] Preparation of 2-tetrahydropyrrole-5,10,15,20-tetrakis(4-chlorophenyl)porphyrin (photosensitizer 2):

[0038] In a 100mL three-necked flask, 2-nitro-5,10,15,20-tetrakis(4-chlorophenyl)porphyrin (183mg, 0.23mmol) was dissolved in N,N-dimethylformamide (20mL) , adding potassium carbonate (360mg, 2.56mmol) and tetrahydropyrrole (0.2mL), heated to reflux for about 3h, and monitored by TLC until the reaction was complete. The reaction solution was evaporated to dryness, and dichloromethane (150 mL) was added for extraction. The organic phase was washed with water (100 mL×3), washed with saturated brine (100 mL×3), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was subjected to column chromatography (eluent: petroleum ether:dichloromethane=3:1) to obtain a purple solid powder 2-tetrahydropyrrole-5,10,15,20-tetrahydropyrrole (4-Chlorophenyl)porphyrin 90.4 mg, yield 48%. 1 H NMR (400MHz, CDCl...

Embodiment 3

[0040] Preparation of 2-piperidine-5,10,15,20-tetrakis(4-chlorophenyl)porphyrin (photosensitizer 3):

[0041] In a 100mL three-necked flask, 2-nitro-5,10,15,20-tetrakis(4-chlorophenyl)porphyrin (183mg, 0.23mmol) was dissolved in N,N-dimethylformamide (20mL) , adding potassium carbonate (360mg, 2.56mmol) and piperidine (0.3mL), heated to reflux for about 3h, monitored by TLC until the reaction was complete. The reaction solution was evaporated to dryness, and dichloromethane (150 mL) was added for extraction. The organic phase was washed with water (100 mL×3), washed with saturated brine (100 mL×3), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was subjected to column chromatography (eluent: petroleum ether: dichloromethane = 3: 1) to obtain a purple solid powder 2-piperidine-5,10,15,20-tetra( 4-chlorophenyl) porphyrin 88.2 mg, yield 46%. 1 H NMR (400MHz, CDCl 3 ): δ8.83-8.81(m, 3H), 8.76-8...

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