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Derivate for labeling bile acid and reference compound, preparation method and application thereof

A technology of bile acid derivatives and compounds, applied in the field of labeling drug derivatives and their reference compounds

Inactive Publication Date: 2010-11-24
SHANGHAI INST OF APPLIED PHYSICS - CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, so far, 99m Tc nuclide labeling of natural ligand bile acids has not been reported in the literature, this is because the use of natural ligand bile acids as raw materials also requires the synthesis of suitable ligands, and then the introduction of 99m Tc coordinated bifunctional chelating agent

Method used

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  • Derivate for labeling bile acid and reference compound, preparation method and application thereof
  • Derivate for labeling bile acid and reference compound, preparation method and application thereof
  • Derivate for labeling bile acid and reference compound, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 5

[0166] The synthesis of embodiment 5 formula V compound

[0167]

[0168] (1) Synthesis of N-ethylamino[bis(2-methylenepyridine)]cholic acid amide tridentate tricarbonyl rhenium chelate

[0169] Among them, A represents -(CH 2 CH 2 ) x -, x=1, R 1 = H, R 2 =α-OH, R 3 =α-OH, the specific synthesis steps are as follows: 100mg (0.158mmol) III was dissolved in 5mL of absolute ethanol, then added (Et 4 N) 2 [Re(CO) 3 Br 3 ]121mg (0.158mmol), reacted at room temperature (25°C) for 1h, evaporated under reduced pressure to remove the solvent, and separated by plate chromatography to obtain 98mg, yield 70%, m.p.125.7~127.4°C.

[0170] The identification data are as follows:

[0171] IR(KBr): v(O-H)3416, v(C=O)1642, v(C=N)1405cm -1 ;

[0172] 1 H NMR (500MHz, CD 3 OD, δ): 0.70(s, 3H, 18-CH3), 0.91(s, 3H, 19-CH 3 ), 0.92~0.98(m, 1H), 1.05(d, 3H, J=6.3Hz, 21-CH3), 1.10~1.17(m, 1H), 1.22~1.30(m, 2H), 1.33~1.46(m , 5H), 1.51~1.68(m, 6H), 1.71~2.08(m, 8H), 2.20~2.38(m, 4H)...

Embodiment 699m

[0226] Example 6 99m Radiochemical Synthesis of Formula III Compounds by Tc

[0227] 1. fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + radiochemical synthesis of

[0228]

[0229] (a) NaBH 4 , Na 2 CO 3 , potassium sodium tartrate, 30min;

[0230] fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + The synthesis of is mainly according to the method of the literature (Journal of Pharmaceutical and Biomedical Analysis, 2007, 43: 1576-1579.), with slight modifications.

[0231] a.15.0mg KNaC 4 h 4 o 6 4H 2 O, 4.0 mg anhydrous Na 2 CO 3 6.0 mg NaBH 4 , mixed in a 10 mL vial.

[0232] b. Charge CO into it for 30 minutes.

[0233] c. Add 1-2ml of freshly rinsed 99m TCO 4 - Solution (10mCi), 70-80 ℃ water bath 30min, ice-water bath cooling, namely fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + .

[0234] 2. Using fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + Steps for radiolabeling N-ethylamino[bis(2-methylenepyridine)]cholic acid amide ligand:

[0235] take fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + Solut...

Embodiment 799m

[0236] Example 7 99m Radiochemical Synthesis of Formula III Compounds by Tc

[0237] 1. fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + radiochemical synthesis of

[0238] The method and conditions are all the same as (1) in Example 6.

[0239] 2. Using fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + Steps for radiolabeling N-ethylamino[bis(2-methylenepyridine)]cholic acid amide ligand:

[0240] take fac-[ 99m Tc(CO) 3 (H 2O) 3 ] + Solution 0.4ml (1.2mci), add 10 -3 mol / L Compound III N-ethylamino[bis(2-methylenepyridine)]cholic acid amide in dimethyl sulfoxide solution 1.2ml, sealed with a parafilm, placed on an incubator, temperature controlled at 65°C, Rotating speed 1000 rev / mins, time 30min, then adopt high performance liquid chromatography (HPLC) [HPLC system: Merck-Hitachi L-7000 system (connected with UV detector and EG&G Berthold LB 508 radioactivity detector), chromatographic column is C- 18ec reverse-phase column, Ф3mm*250mm, 5μm; HPLC elution gradient (solution A: anhydrous m...

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Abstract

The invention discloses a derivate for labeling bile acid shown in formula VI, wherein A is -(CH2CH2)x- or -(CH2CH2O)m(CH2CH2)n-, x=1-4, preferably 1 or 3, m=1-3, preferably 1, n=1, and R1,R2 and R3 are hydrogen, alpha-OH or beta-OH respectively. The invention also provides a reference compound, a preparation method and an application of the derivate for labeling bile acid. The invention utilizes radioactive nuclide 99mTc to indirectly label bile acid for the first time, and the derivate for labeling bile acid in the invention has good application prospect of raster display.

Description

technical field [0001] The present invention relates to a labeled drug derivative and its reference compound, as well as its preparation method and application, in particular to a labeled bile acid derivative and its reference compound, its preparation method and its application. Background technique [0002] Nuclear medicine can use the special physical properties of labeled nuclides in certain radiopharmaceuticals to image a variety of tumors and their lesions. This unique method of tumor diagnosis has been paid more and more attention in clinic. Currently, radionuclides used for imaging mainly include 131 I. 153 Sm, 117m Sn, 186 Re, 188 Re and 99m Tc et al. in, 99m Tc has attracted much attention in the field of tumor diagnosis because of its excellent physical and chemical properties. 99m The half-life of Tc is 6.01 hours, the energy of gamma rays is 140keV, the radiation damage is small, and it has good imaging resolution, and it can be easily obtained from 99...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J43/00C07F13/00C07J41/00A61K51/04A61K103/10
Inventor 沈玉梅黄立梁朱华张春春
Owner SHANGHAI INST OF APPLIED PHYSICS - CHINESE ACAD OF SCI
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