Bisamidocyanogen androstanes derivates, preparation method and use thereof

A technology of bisaminoandrostane and derivatives is applied in the directions of steroids, drug combinations, pharmaceutical formulations, etc., to achieve the effects of rapid onset of action, short duration of maintenance, and strong muscle relaxation.

Inactive Publication Date: 2009-03-25
NANJING MESE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, shortly after racuronium bromide was used in clinical anesthesia, 21 cases of sev...

Method used

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  • Bisamidocyanogen androstanes derivates, preparation method and use thereof
  • Bisamidocyanogen androstanes derivates, preparation method and use thereof
  • Bisamidocyanogen androstanes derivates, preparation method and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1: Synthesis of 2β, 16β-bis(1-piperidinyl)-3α, 17β-acetoxy-5α-androstane (A-6)

[0025] Using 5α-androst-2-en-17-one as raw material, it is prepared by esterification of isopropenyl acetate, oxidation of m-chloroperoxybenzoic acid, ring-opening addition with piperidine, reduction of sodium borohydride, and acetylation of acetyl chloride Compound A-6, specific preparation method references: Buckett W.R.; Hewett C.L.; Savage D.S.. Pancuronium Bromide and Other Steroidal Neuromuscular Blocking Agents Containing Acetylcholine Fragments

[0026] [J]. J. Med. Chem, 1973, 16(10): 1116-1124.

Embodiment 2

[0027] Example 2: 1-[3α,17β-diacetoxy-2β(1-piperidinyl)-5α-androstane-16β-yl]-1-acetonitrile piperidine bromide (A-8)

[0028] Dissolve A-6 (4.5g, 8.3mmol) in a mixed solution of acetonitrile (40mL) and acetone (10mL), add bromoacetonitrile (11g, 92mmol), carry out nitrogen protection, stir at room temperature for 40h, and concentrate under reduced pressure. Acidified alumina column chromatography, eluting with isopropanol-ethyl acetate (volume ratio = 2:5) to give an oily product, refined with acetone, and dried to give off-white solid A-8 (3.2 g, yield 51.2%) , mp: 148.8-151.3℃.

[0029]

[0030] 1 HNMR (DMSO-d 6 )H-Hcosy, HSQC δ ppm: 0.70-0.72 (1H, m, 9-position CH, related to 9-position C), 0.75 (3H, s, 18-position CH 3), 0.97 (3H, s, 19 CH 3 ), 0.94-0.99, 1.68-1.71 (2H, m, 28 CH 2 , related to 27, 29 H), 1.21-1.25 (1H, m, 14 CH, related to 8, 15 H), 1.25-1.27 (2H, m, 6 CH 2 , related to 5 and 7 H), 1.24-1.32, 1.69-1.73 (2H, m, 7 CH 2 , related to 6 and 8-positio...

Embodiment 3

[0033] Example 3: 1,1'-[3α,17β-diacetoxy-5α-androstane-2β,16β-diyl]-bis[1-acetonitrile piperidine](A-9) dibromide

[0034] Dissolve A-6 (4.5g, 8.3mmol) in a mixed solution of acetonitrile (40mL) and acetone (10mL), add bromoacetonitrile (21g, 175mmol), under nitrogen protection, stir at about 40°C for 40h, and concentrate under reduced pressure , the product was subjected to alumina (75-240 mesh) column chromatography, eluted with isopropanol-ethyl acetate (volume ratio = 3:1) to obtain an oil, refined with acetone, and dried to obtain an off-white solid A-9 ( 2.8g, yield 43.7%), mp: 147.8-150.9°C.

[0035]

[0036] 1 HNMR (DMSO-d 6 )H-Hcosy, HSQC δ ppm: 0.79 (3H, s, 18 CH 3 ), 0.88-0.99 (1H, m, 9-position CH, related to 9-position C), 0.89 (3H, s, 19-position CH 3 ), 0.88-0.90, 1.63-1.69 (2H, m, 7 CH 2 , related to 6 and 8-bit H), 1.02-1.06 (1H, m, 2-bit-N + CH-), 1.10-1.18, 1.40-1.44 (2H, m, 6 CH 2 , related to 5, 7 H), 1.22-1.33 (1H, m, 14 CH, related to 8, 15 H),...

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PUM

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Abstract

The invention discloses a diamino etioallocholane derivative, a preparation method and the application thereof. The structure of the derivative is shown as the formula (I) or the formula (II), wherein, R1 or R2 is respectively C1-4 alkyl, C1-4 nitrile group or C1-4 alkynyl independently; R3 is C2-4 alkyl, C1-4 nitrile group or C1-4 alkynyl. Through the determination of activity, the compound has stronger muscle-relaxing action, and the holding time of one-time intravenous thereof is short.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and specifically relates to a diaminoandrostane derivative, a preparation method and an application thereof. Background technique [0002] 1996 was the 150th anniversary of William Morton's public demonstration of ether anesthesia at the Massachusetts General Hospital in Boston, USA, and also the 150th anniversary of the founding of modern anesthesiology. Since then, it has developed very slowly in the first nearly 100 years, and there are only a few kinds of anesthetics, and the anesthesia technique is also very simple. Since Griffiths and Johnson first used neuromuscular blockers in 1942, they have revolutionized the old anesthesia method, using balanced anesthesia to replace the method of completing anesthesia with a single anesthetic, that is, using different drugs to complete the three purposes of anesthesia , sleep-pain relief-muscle relaxation, opened a new era of surgery. Neuromuscular...

Claims

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Application Information

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IPC IPC(8): C07J43/00A61K31/58A61P21/02
Inventor 季刚李飞王殿广陈萍赵萍
Owner NANJING MESE PHARMA
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