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Preparation method of deuterium-labeled betamethasone

A technology of betamethasone and deuterium labeling, which is applied in the fields of organic chemistry methods, chemical instruments and methods, steroid isotope introduction, etc., can solve the problems such as no synthesis report of betamethasone deuterium-labeled compounds, and achieve easy labeling and good stability , the effect of high yield

Active Publication Date: 2018-08-24
TLC NANJING PHARMA RANDD CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

There are no reports on the synthesis of betamethasone deuterium-labeled compounds at home and abroad

Method used

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  • Preparation method of deuterium-labeled betamethasone
  • Preparation method of deuterium-labeled betamethasone
  • Preparation method of deuterium-labeled betamethasone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] A preparation method of deuterium-labeled betamethasone, such as figure 1 shown, including the following steps:

[0036] (1) Preparation of compound III:

[0037]

[0038] 30 g of betamethasone (compound II) was suspended in 400 ml of chloroform and 600 ml of 7 mol / L hydrochloric acid mixed solvent, and 64.21 g of paraformaldehyde was added in an ice bath. The reaction mixture was stirred at 30°C for 3 hours, the reaction solution was extracted three times with 300 ml of chloroform, and spin-dried to obtain 30.2 g of crude product, which was crystallized with methanol and dichloromethane to obtain 28 g of compound III, with a yield of 84.4%, MS: 435.5 [M+ H] + . 1 H NMR (400MHz, CDCl 3 ):δ0.88(s,3H),1.1(m,4H),1.52(s,3H),1.60~2.7(9H),3.35(m,1H),3.99~4.18(dd,2H),4.35( s,1H),4.85(s,1H),5.07(d,2H),5.13(s,1H),6.17(s,1H),6.27(d,1H),7.45(d,1H).

[0039] (2) Preparation of Compound IV:

[0040]

[0041] Suspend 10 g of compound III in 400 ml of dichloromethane, add...

Embodiment 3

[0074] Anti-inflammatory and anti-allergic experiments of embodiment 3 deuterium-labeled betamethasone

[0075] 1. Xylene-induced mouse auricle swelling experiment (mouse ear swelling method)

[0076] Get 60 mice, be divided into 7 groups at random, namely blank control (normal saline) group, model group, aspirin group and deuterium-labeled betamethasone (compound I) (0.05g / ml) intragastric administration, continuous 3d, The volume of administration is 0.1ml / 10g. One hour after the last administration, smear 0.05ml of xylene on both sides of the right ear of the mouse evenly, and the left ear is not applied as a control. Ear pieces were punched at the same position in both ears, and the weight of the ear pieces was weighed on an analytical balance. The difference in weight was used as the degree of swelling, and the swelling inhibition rate was calculated.

[0077] Ear swelling (%) = (right ear weight - left ear weight) / left ear weight × 100%

[0078] Inhibition rate of ea...

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Abstract

The invention discloses a preparation method of deuterium-labeled betamethasone. The method is characterized in that betamethasone is used as an initiator and the deuterium-labeled betamethasone is synthesized through five-step reaction. According to the preparation method disclosed by the invention, optimal preparation steps and reaction conditions are screened out through a large number of experiments; the whole technology is reasonable in design and the operability is high. The deuterium-labeled betamethasone prepared by the preparation method disclosed by the invention has the characteristics that the purity can reach 98 percent or above, the yield is high, and isotope abundance is greater than 97 percent. The deuterium-labeled betamethasone prepared by the preparation method disclosedby the invention has the advantages that test and control samples can be provided for the study on a metabolic mechanism and an anti-inflammatory mechanism of the betamethasone; in addition, the deuterium-labeled betamethasone has important potential anti-inflammatory value and other application value.

Description

technical field [0001] The invention belongs to the technical field of isotope-labeled drug synthesis, and relates to a preparation method of deuterium-labeled betamethasone. Background technique [0002] Betamethasone is a steroidal potent glucocorticoid with anti-inflammatory, anti-allergic, and anti-immune effects, and is widely used in dermatology. The pure product is white or off-white loose lump or powder. The chemical name is (8S,9R,10S,11S,13S,14S,16S,17R)-9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7 ,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one, the molecular weight is 392.46, the molecular formula is C22H29FO5, and the structural formula is as follows: [0003] [0004] Deuterium is a non-radioactive stable isotope of hydrogen, symbol D. The isotopic abundance of deuterium in nature is about 0.016%. The deuterium-labeled compound is a compound in which hydrogen atoms or part of hydrogen atoms in the compou...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J5/00C07J71/00C07B59/00
CPCC07B59/007C07B2200/05C07J5/0076C07J71/0005
Inventor 杨石陈国雨张池易天
Owner TLC NANJING PHARMA RANDD CO LTD
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