Positive electron medicine [18F] FPMMP as well as preparation method and midbody thereof

A positron and intermediate technology, applied in the field of 18F positron tracer synthesis, can solve the problems of less than 1 binding ability in vivo, general targeting ability in vivo, unfavorable promotion and use, etc.

Active Publication Date: 2018-03-23
JIANGSU RENMING BIOLOGICAL TECH CO LTD
View PDF6 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Although scientists have conducted a large number of PET studies on the above three tracers to prove their role in quantitatively characterizing the concentration of SV2A targets in vivo, they have not been widely used clinically due to their own limitations: UCB-A and Although the synthesis of UCB-H is relatively convenient, its in vivo targeting ability is average, and its in vivo binding ability (BP ND ) are less than 1, which is unfavorable for popularization; UCB-J has the best targeting performance in vivo, and the BP in the cortex ND The value exceeds 3, and the hippocampus also has 1.6. It is a very potential tracer, but its labeling method requires the use of metal-mediated coupling reactions, which is difficult to achieve in PET centers in many hospitals. More importantly, The peak time in the brain of this tracer often exceeds 40 minutes, and the kinetic speed is too slow to meet clinical needs

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Positive electron medicine [18F] FPMMP as well as preparation method and midbody thereof
  • Positive electron medicine [18F] FPMMP as well as preparation method and midbody thereof
  • Positive electron medicine [18F] FPMMP as well as preparation method and midbody thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1 Synthesis of Side Chain Pyridine Ring System Components

[0054]

[0055] 1 (10g, 66mmol) was dissolved in anhydrous methanol (132mL), sodium borohydride (3.75g, 99mmol) was added gradually at 0°C, and the temperature was slowly raised to 60°C under nitrogen protection and stirred overnight. The next day, the reaction system was lowered to 0°C, and ice water was added dropwise to the mixed system, and the reaction was carefully quenched until the system stopped bubbling, then the reaction system was poured back into ice water (200 mL), and extracted 3 times with ethyl acetate (100mL x 3). The organic phases were combined, backwashed 5 times with saturated brine (50mL x 5), dried over anhydrous magnesium sulfate, filtered, and concentrated. The obtained crude product was separated and purified by column chromatography (ethyl acetate:n-hexane=1:1), and the product 2 was obtained as a light yellow solid with a yield of 6.89g and a yield of 85%.

[0056] 1...

Embodiment 2

[0059] Example 2 Synthesis of Standard Compounds

[0060]

[0061] Potassium carbonate solution is prepared in advance: Dissolve 16.8g of potassium carbonate in 20mL of water.

[0062] Under nitrogen protection, dissolve m-fluorophenylboronic acid 4 (71.8mmol, 10g) in toluene (200mL) solution at room temperature, add [RhCl(COD)] 2 Catalyst (0.9mmol, 0.45g). After stirring for 30 minutes, substrate 5 (30.0mmol, 5.5g) and the above potassium carbonate solution were added successively, and the mixture was slowly raised to 60°C for 12 hours. After cooling down to room temperature, dilute with 100 mL of water, extract three times with ethyl acetate (50 mL x 3), combine the organic phases, backwash once with saturated brine (50 mL), dry over anhydrous magnesium sulfate, filter, and concentrate. The obtained crude product was separated and purified by column chromatography (ethyl acetate:n-hexane=1:10), and the product 6 was obtained as a yellow solid with a yield of 5.27g and ...

Embodiment 3

[0071] Example 3 Synthesis of corresponding iodo compounds

[0072]

[0073] The operation method was the same as the preparation method of compound 6, and the product 10 was separated by silica gel column chromatography as a light yellow liquid with a yield of 81%.

[0074] 1 H NMR (400MHz, CDCl 3 ):7.41(d,1H,J=6.4Hz),7.39(s,1H),7.24(dd,1H,J=11.6,5.6Hz),7.17(d,1H,J=6.0Hz),4.15(dd ,1H,J=8.8,6.8Hz),3.67(dd,1H,J=8.8,6.8Hz),3.51(t,1H,J=7.2Hz),2.89(q,1H,J=6.8Hz),2.68 (q,1H,J=8 Hz),1.54(s,9H);HRMS(EI)m / z calculated for C 15 h 19 BrNO 3 [M+H] + :341.0548, found 341.0543.

[0075]

[0076] The operation method was the same as the preparation method of compound 7, and the product 11 was separated by silica gel column chromatography as an anhydrous liquid, and the yield was 90%.

[0077] 1 H NMR (400MHz, CDCl 3 ):7.41-7.39(m,2H),7.24-7.17(m,2H),6.49(br s,1H),3.79(t,1H,J=7.2Hz),3.67(t,1H,J=6.4Hz ),3.41(q,1H,J=6.0Hz),2.74(q,1H,J=7.2Hz),2.48(q,1H,J=7.2Hz); HRMS(EI)m / z c...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to a positive electron medicine [18F] FPMMP as well as a preparation method and a midbody thereof. The positive electron medicine [18F] FPMMP has a following structure shown in the description. The positive electron medicine [18F] FPMMP can reach the peak value after 10 minutes after the injection to the brain part of the non-human primate animals; the clinic use is convenient; the BPND can reach 2.14 in a cingulate cortex.

Description

technical field [0001] The invention belongs to 18 F positron tracer synthesis field, specifically related to a kind of positron drug [ 18 F] FPMMP and its preparation method and intermediate. Background technique [0002] The release of neurotransmitters from synaptic vesicles at the nerve terminal is a delicate and complex process involving the interaction between a variety of proteins, among which vesicle protein 2 (synaptic vesicle protein 2, SV2) located on the synaptic vesicle membrane is located in the central nervous system. Plays a key role in maintaining nervous system function. The main isoform SV2A in this family of proteins contains 12 hydrophobic transmembrane regions (TMR) and an intrasynaptic vesicle macroloop containing 3 N-glycosylation sites, the latter corresponding to amino acid 498 (N1) , amino acid 548 (N2) and amino acid 573 (N3). [0003] Surgical resection specimens from patients with temporal lobe epilepsy (TLE) showed that the expression of SV...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/06C07D405/14C07D409/14A61K51/04A61K101/02
CPCA61K51/0455C07B2200/05C07D401/06C07D405/14C07D409/14
Inventor 郑超赵新阳秦伟
Owner JIANGSU RENMING BIOLOGICAL TECH CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap