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Kyotorphin modified fatty amine/alcohol derivative, and preparation method and application thereof

A compound and anti-inflammatory drug technology, applied in the field of artificially synthesized polypeptide compounds, can solve the problems of poor oral activity

Inactive Publication Date: 2014-01-22
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the design of analgesics, the inventors realized that Kyoto phenol (Tyr-Arg) is a potential analgesic dipeptide, and its poor oral activity

Method used

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  • Kyotorphin modified fatty amine/alcohol derivative, and preparation method and application thereof
  • Kyotorphin modified fatty amine/alcohol derivative, and preparation method and application thereof
  • Kyotorphin modified fatty amine/alcohol derivative, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Example 1 prepares N G -Arg(NO 2 )

[0022] Under the condition of ice-salt bath stirring, add 80ml concentrated nitric acid to 500ml eggplant bottle, then slowly add 80ml concentrated sulfuric acid. After 10 min, 47.33 g (272 mmol) of L-Arg was added in batches, and the reaction mixture was stirred and reacted for 2 h in an ice-salt bath. Slowly add 96ml of ice water to the reaction mixture, then slowly add concentrated ammonia water, adjust the pH to 8, then adjust the pH to 6 with glacial acetic acid, a large amount of colorless solid precipitates, put it in a refrigerator at 4°C to continue crystallization. Filter under reduced pressure, discard the filtrate, dissolve the filter cake with hot water at 80°C, and put it in a refrigerator at 4°C for recrystallization. Filter under reduced pressure at room temperature to collect 52.5 g of insoluble matter as a colorless solid with a yield of 88%. ESI-MS (m / e): 220 [M+H] + .

Embodiment 2

[0023] Embodiment 2 prepares N α -Boc-N G -Arg(NO 2 )

[0024] Weigh 1.752g (8mmol) N G -Arg(NO 2 ) into the reaction bottle, add 3ml of water to dissolve, under the condition of ice bath, slowly add 8ml of 1N NaOH dropwise, will dissolve 1.92g (Boc) 2 Slowly pour the dioxane of O into it, adjust the pH of the reaction solution to 9, and react for 48 hours. During this period, the CO in the reaction system is pumped every 2 hours 2 once. After the reaction is complete as detected by TLC, adjust the pH of the reaction solution to 7, spin off dioxane, then adjust the pH of the reaction solution to 2, extract the reaction solution three times with ethyl acetate, and then wash the ethyl acetate layer three times with saturated NaCl , to obtain the ethyl acetate layer with anhydrous NaSO 4 Dry overnight, filter to remove NaSO 4 , spin-dried ethyl acetate to obtain 2.4 g of the title compound as a colorless solid, yield 94%. ESI-MS (m / e): 320 [M+H] + .

Embodiment 3

[0025] Embodiment 3 prepares N G -Arg(NO 2 )-OBzl

[0026] Take 6.57g (30mmol) N G -Arg(NO 2 ) into the reaction flask, then add 6.21g of sodium benzenesulfonate, 50ml of benzyl alcohol, and 20ml of cyclohexane, and react in an oil bath at 80°C for 8h. , to obtain 14.1 g of the title compound as a colorless solid, with a yield of 98%. ESI-MS (m / e): 310 [M+H] + .

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Abstract

The invention discloses a kyotorphin (Tyr-Arg) modified fatty amine / alcohol derivative, a preparation method and application thereof in serving as an analgesic and an anti-inflammatory agent. The structure of the kyotorphin modified fatty amine / alcohol derivative has a general formula I, Tyr-Arg-XCH2(CH2)nCH3, wherein X represents NH or O, and n is 6, 8, 10, 12, 14 or 16. According to the kyotorphin modified fatty amine / alcohol derivative, the analgesic activity of the compound shown in the general formula is evaluated by adopting a mouse thermal tail-flick method model; the anti-inflammation activity of the compound shown in the general formula I is evaluated by adopting a mouse ear swelling model; an experimental result reflects that the 12 compounds represented by the general formula I have excellent analgesic activity and relatively high anti-inflammation activity under the condition of the same dosage; and the kyotorphin modified fatty amine / alcohol derivative can be applied to production of analgesics and anti-inflammatory agents.

Description

technical field [0001] The present invention relates to an artificially synthesized polypeptide compound, in particular to a compound obtained by protecting and modifying the carboxyl end of a dipeptide with fatty amine and fatty alcohol, its preparation method and its use in the preparation of analgesic and anti-inflammatory drugs. application. Background technique [0002] As one of the main vital signs of human beings, pain has important biological significance. The World Pain Conference recognized pain as the "fifth vital sign of human beings" after breathing, pulse, body temperature and blood pressure, and many patients are suffering from pain. At present, the analgesics used clinically have their own side effects, such as the addiction of opioid analgesics and the irritation of salicylic analgesics to the gastrointestinal tract. Finding analgesics is a hot spot in the research of new drugs one. In the design of analgesics, the inventors realized that kyotophenol (Ty...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K5/065C07K1/06A61K38/05A61P29/00
CPCY02P20/55
Inventor 赵明彭师奇于言言
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES