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4-methoxy methyl-4-(N-propionyl) aniline piperidine compound and preparation method and application thereof

A technology of methoxymethyl and aniline piperidine, applied in the field of 4-methoxymethyl-4-aniline piperidine compounds, which can solve problems such as slow recovery, waste of medical resources, and increased operational complexity

Active Publication Date: 2012-08-01
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to its rapid metabolism, anesthesiologists need to adjust the dosage of the two drugs at any time during the operation to maintain an effective drug concentration, which increases the complexity of the operation. Therefore, many clinical doctors prefer to use analgesia Alfentanil and midazolam, which have a longer sedation time, will slow the recovery of patients after surgery, prolong the stay in the operating room, and lead to a waste of medical resources to a certain extent

Method used

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  • 4-methoxy methyl-4-(N-propionyl) aniline piperidine compound and preparation method and application thereof
  • 4-methoxy methyl-4-(N-propionyl) aniline piperidine compound and preparation method and application thereof
  • 4-methoxy methyl-4-(N-propionyl) aniline piperidine compound and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] Dissolve the compound of formula (Ⅳ) (CAS number: 61086-18-8) (65 mg, 0.236 mmol) and acrylic acid (51 mg, 0.708 mmol) in 20ml di Chloromethane, stirred overnight at room temperature. After the reaction solution was concentrated, it was purified by preparative thin layer (dichloromethane / methanol=8:1) to obtain 56 mg of a yellow oily intermediate, with a yield of 68%.

[0018] .

[0019] This intermediate (56 mg, 0.161 mmol), Cs 2 CO 3 (105 mg, 0.322 mmol) and (55 mg, 0.241 mmol) were dissolved in 10ml of acetone and stirred overnight at room temperature. After the reaction solution was concentrated, it was purified by thin layer (developing solvent: cyclohexane / ethyl acetate = 1:1), and n=2 and R in the formula (I) were 30 mg of yellow oily product, yield 34%.

[0020] Product structure detection results:

[0021] NMR instrument: Bruker WH-300 (300 MHz) spectrometer, TMS is the internal standard, and the unit of δ is ppm.

[0022] Mass spectrometer: Agilent ...

Embodiment 2

[0026] The compound of formula (IV) (138 mg, 0.5 mmol), triethylamine (253 mg, 2.5 mmol) (or pyridine 200 mg, 2.5 mmol) and 3-bromo-n-propanol ( 348 mg, 2.5 mmol) was dissolved in 4ml of dichloromethane, stirred overnight at room temperature. After the reaction solution was concentrated and purified by thin layer (developing solvent: dichloromethane / methanol = 6:1), 170 mg of a yellow oily intermediate was obtained, with a yield of 99% (when the acid removal agent was pyridine, 160 mg of the intermediate was obtained, with a yield of 93%).

[0027] After propofol chloroformate was prepared from propofol and phosgene according to the reported method, the above-mentioned intermediate (170 mg, 0.5 mmol), triethylamine (101 mg, 1 mmol) and propofol Porphenol chloroformate was dissolved in 20ml of dichloromethane, stirred overnight at room temperature, and the reaction solution was concentrated and purified by preparative thin layer (developing solvent: cyclohexane / ethyl acetate =...

Embodiment 3

[0034] Pharmacological activity experiment:

[0035] 1. Anesthetic activity test:

[0036] 20 male Kunming mice with a body weight of 20-30 grams were randomly divided into 4 groups, and the compound of the present invention was prepared into a solution with normal saline, and 5 mice in each group were administered via the tail vein, and the disappearance of the righting reaction was observed. No, as an indicator of narcotic effects. The results of the anesthetic activity experiments are shown in Table 1.

[0037] Table 1 The anesthetic activity test result of the compound of the present invention

[0038] compound Dose (mg / kg) Is the righting reflex gone? normal saline — no Propofol 15 yes

[0039] The results in Table 1 show that the compound of the present invention has an anesthetic effect and can cause the reversible disappearance of righting reflex in mice.

[0040] 2. Analgesic activity test:

[0041]At room temperature of 20°C, ...

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Abstract

The invention relates to a 4-methoxy methyl-4-(N-propionyl) aniline piperidine compound and a preparation method and application thereof. The structure of the compound is shown in Formula (I), wherein n is 2 or 3 and R is optional. The compound has good water solubility and stability and can achieve analgesic and sedative effects simultaneously. Thus, the compound is applicable to analgesia and sedation of patients needing postoperative care, and is particularly conducive to operation of the automatic dosing system by patients, and the operations by anesthesia doctors can be reduced.

Description

technical field [0001] The invention relates to a compound with general anesthesia and analgesic effect, especially 4-methoxymethyl-4-(N-propionyl)aniline piperidine compound, a preparation method and pharmaceutical use of the compound. Background technique [0002] In the medical activities of clinical operation and postoperative monitoring, the combined use of analgesia, sedation and anesthesia drugs ensures the patient's surgical compliance. The current clinical anesthesia is monitored anesthesia under the control of doctors. Anesthesiologists need to pay attention to the patient's vital signs at any time and carry out targeted treatment of the patient's pain. The realization of these treatments mainly depends on the use of various analgesic and sedative drugs. Currently commonly used analgesic drugs are opioid agonists, such as fentanyl and remifentanil. Remifentanil (Remifentanil, 3 [4 (methoxycarbonyl) - 4- (N-phenylpropanylamino) 1-piperidine] propionate methyl este...

Claims

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Application Information

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IPC IPC(8): C07D211/58A61K31/4468A61P25/20A61P23/00A61P29/00
Inventor 刘进张文胜杨俊
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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