Dopamine transporter imaging medicine and preparation method thereof

A transporter and dopamine technology, applied in the field of dopamine transporter imaging drugs and its preparation, can solve the problems of poor specific selectivity, low ratio of drug target to non-target, and poor stability in vivo

Inactive Publication Date: 2012-01-11
BEIJING NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the currently researched benztropine PET imaging agents often have the following defects, such as low target-to-non-target ratio of the drug, poor specific selectivity, poor stability in vivo, etc., which affect the clinical imaging effect

Method used

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  • Dopamine transporter imaging medicine and preparation method thereof
  • Dopamine transporter imaging medicine and preparation method thereof
  • Dopamine transporter imaging medicine and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Synthesis of 2β-(N-2-bromopyridine-6-carboxamide)-3βchlorobenzene A-1

[0033] (1) The structure of the compound

[0034]

[0035] (2) Synthesis method

[0036] Add 280mg (1mM) 2β-carboxy-3βchlorophentropine and 5ml of anhydrous dichloromethane in a single-necked round-bottomed flask, add dropwise an excess of 1.5ml of oxalyl chloride in dichloromethane solution, and react at room temperature After 1.5 hours, the solvent and unreacted oxalyl chloride were pumped off with a water pump, and then dried with an oil pump to obtain a foamy solid. Then add 5 ml of dichloromethane to dissolve the obtained solid, and add 172 mg (1 mM) of 6-amino-2-bromopyridine and 0.14 ml (1 mM) of triethylamine under nitrogen protection using an ice-salt bath. After reacting at room temperature for 12 hours, stop the reaction, wash the reaction solution repeatedly with deionized water, and back-extract with dichloromethane, combine the dichloromethane layers, dry over anhydrous sodium sul...

Embodiment 2

[0042] Synthesis of 2β-(N-2-bromopyridine-6-methylamine)-3βchlorobenzene B-1

[0043] (1) The structure of the compound

[0044]

[0045] (2) Synthesis method

[0046] Dissolve 0.5g of A-1 in 4ml of THF, add dropwise 3ml of 1M borane THF solution under nitrogen protection, heat to reflux, react for 12 hours, then stop the reaction, remove the solvent under reduced pressure, add 3mL of 1N hydrochloric acid to the residue , boiled for 30min, cooled to room temperature, neutralized with 5mL ammonia water, the obtained precipitate was extracted with dichloromethane, dried over anhydrous sodium sulfate, purified by silica gel chromatography, the solvent ratio was ethyl acetate: n-hexane: triethylamine=6:4 : 0.3, a yellow foamy solid was obtained with a yield of 70%.

[0047] (3) Confirmation of B-1

[0048] h 1 -NMR (CDCl 3, 200MHz): δ (ppm) 1.5-1.8 (m, 3H), 1.8-2.0 (m, 2H), 2.1-2.5 (m, 2H), 2.4-2.5 (s, 3H), 2.8-2.9 (dt, 1H), 3.1-3.3(dt, 2H), 3.3-3.4(t, 2H), 5.9-6.1(d, 2H)...

Embodiment 3

[0052] Synthesis of 2β-(N-2-bromopyridine-5-carboxamide)-3βchlorobenzene A-2

[0053] (1) The structure of the compound

[0054]

[0055] (2) Synthesis method

[0056] Add 280mg (1mM) 2β-carboxy-3βchlorophentropine and 5ml of anhydrous dichloromethane in a single-necked round-bottomed flask, add dropwise an excess of 1.5ml of oxalyl chloride in dichloromethane solution, and react at room temperature After 1.5 hours, the solvent and unreacted oxalyl chloride were pumped off with a water pump, and then dried with an oil pump to obtain a foamy solid. Then add 5 ml of dichloromethane to dissolve the obtained solid, and add 172 mg (1 mM) of 5-amino-2-bromopyridine and 0.14 ml (1 mM) of triethylamine under nitrogen protection using an ice-salt bath. After reacting at room temperature for 12 hours, stop the reaction, wash the reaction solution repeatedly with deionized water, and back-extract with dichloromethane, combine the dichloromethane layers, dry over anhydrous sodium sul...

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PUM

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Abstract

The invention relates to a medicine for developing a dopamine transporter and a preparation method thereof. The medicine has the structure described in the specification, wherein X= -CH2 or -C=O, and R=Br or F18. Novel serial 2 beta amide / amino-3 beta chlorobenzene tropine derivatives containing pyridine groups are designed and synthesized by using 2 beta-carboxyl-3beta chlorobenzene tropine as alead compound, have higher targeting, can be specifically combined with DAT, can be used for marking F-18 by introducing a pyridine ring structure, can be used for carrying out PET development research, and are PD diagnosis developer with favorable application potential.

Description

technical field [0001] The invention relates to a dopamine transporter imaging medicine and a preparation method thereof, in particular to a dopamine transporter target imaging medicine and a preparation method thereof. Background technique [0002] Dopamine transporter (dopamine transporter, DAT) is a kind of membrane protein located in the presynaptic membrane of dopaminergic neuron terminals in substantia nigra-striatum, and it is the uptake site of dopamine. In the brain, the main function of DAT is to re-uptake the excess dopamine neurotransmitter in the synaptic gap back into the dopamine neuron, so as to limit the time, degree and scope of dopamine receptor activation, terminate the transmission of information between nerve cells, and at the same time regulate The level of dopamine in the synaptic cleft maintains the synthesis and storage function of presynaptic dopamine. If the reuptake function of DAT is abnormal, the concentration of DA in the synaptic cleft will ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K51/04C07D451/02A61K101/02
Inventor 朱霖刘晶莹
Owner BEIJING NORMAL UNIVERSITY
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