469-79-4

Basic information

• Product Name: ketobemidone
• Synonyms: ketobemidone;1-[4-(3-Hydroxyphenyl)-1-methylpiperidin-4-yl]-1-propanone;Cetobemidone;Ethyl 4-(3-hydroxyphenyl)-1-methylpiperidin-4-yl ketone;1-[4-(m-Hydroxyphenyl)-1-methyl-4-piperidyl]-1-propanone;1-Propanone, 1-[4-(3-hydroxyphenyl)-1-methyl-4-piperidinyl]-;1-Propanone, 1-[4-(m-hydroxyphenyl)-1-methyl-4-piperidyl]-;A 21 Lundbeck
• CAS NO: 469-79-4
• Molecular Formula: C₁₅H₂₁NO₂
• Molecular Weight: 247.37
• EINECS: 207-421-0
• Product Categories: Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 469-79-4.mol
• Article Data: 5

Chemical Properties

• Melting Point: 156-157°
• Boiling Point: 390.37°C (rough estimate)
• Flash Point: 190.4 °C
• Appearance: /
• Density: 1.0267 (rough estimate)
• Vapor Pressure: 1.11E-06mmHg at 25°C
• Refractive Index: 1.5130 (estimate)
• Solubility: Freely soluble in water, soluble in ethanol (96 per cent), very slightly soluble in methylene chloride.
• PKA: pKa 8.52/9.65(H2O) (Uncertain)
• CAS DataBase Reference: ketobemidone(CAS DataBase Reference)
• NIST Chemistry Reference: ketobemidone(469-79-4)
• EPA Substance Registry System: ketobemidone(469-79-4)

Safety Data

• Hazardous Substances Data: 469-79-4(Hazardous Substances Data)

Usage

Chemical Properties

ketobemidone is white or almost white, crystalline powder.

Originator

Ketobemidone,Shanghai Lancheng Corporation

Uses

ketobemidone is an opioid analgesic. Used as a substitute to morphine for postoperative pain in children.

Manufacturing Process

The process includes the following steps: 1. 80 weight parts (w.p.) powder of sodium amide was added to 147 w.p. 3- methoxy-benzylcyanide, 156 w.p. N,N-bis(2-chloroethyl)-N-methylamine and 350 w.p. toluene in 6-8 portions by stirring at 40°-45°C. The mixture was slowly heated to 100°-105°C with stirring for 1 hour at this temperature. Some water was added after cooling, the toluene layer was treated with diluted HCl and it therefrom was adjusted to a alkaline pH by addition of sodium hydroxide, extracted with ether and the ether layer dried over Na2CO3. The solvent was removed; the distillation of the residue gave 4-cyan- 4-(3-metoxyphenyl)-1-methylpiperidine as a colorless oil; BP 150°C at 2 mm/Hg, hardened by standing; MP 44°C. The yield was 65-68%. 2. The solution of ethyl magnesium bromide from 36 w.p. magnesium and 165 w.p. ethyl bromide in 700 w.p. ether was added to 230 w.p. above cyanide in 330 w.p toluene. The mixture was refluxed for 1 hour. Then the ether was slowly distilled and the residue was stood for 1 hour at water bath temperature. After cooling with an ice the mixture was acidified by addition of HCl to adjust the congo acid pH. 4-(3-Methoxyphenyl-1-methyl-4- propipnylpiperidine was prepared by a saturation of above solution with NH3 and it therefrom was dried over K2CO3 and distilled to give a colorless product BP 184°-185°C at 6 mm/Hg. 3. The mixture 261 w.p 4-(3-methoxyphenyl)-1-methyl-4-propipnylpiperidine and 750 w.p. HBr (BP 126°C) was refluxed for 1 hour. Then 2/3 of acid was distilled on an oil bath and the hot water was added to the rest. The title product was precipitated by NH3 as the oil that became hard and after recrystallisation from ethylacetate had MP 156°-157°C.

Therapeutic Function

Narcotic analgesic

InChI:InChI=1/C15H21NO2/c1-3-14(18)15(7-9-16(2)10-8-15)12-5-4-6-13(17)11-12/h4-6,11,17H,3,7-10H2,1-2H3

Upstream product

• 55-86-7 mechlorethamine hydrochloride 
• 105-59-9 N-Methyldiethanolamine 
• 51-75-2 nitrogen mustard 
• 19924-43-7 3-methoxyphenylacetonitrile 
• 50-00-0 formaldehyd 
• 15847-72-0 Norketobemidone 
• 43152-59-6 1-[4-(3-methoxy-phenyl)-1-methyl-piperidin-4-yl]-propan-1-one 
• 5460-79-7 1-methyl-4-(m-methoxyphenyl)-4-cyanopiperidine 

Downstream Products

• 107419-07-8 1-[4-(3-acetoxy-phenyl)-1-methyl-[4]piperidyl]-propan-1-one 
• 87764-56-5 1-[4-(3-ethoxycarbonyloxy-phenyl)-1-methyl-[4]piperidyl]-propan-1-one 

Relevant articles and documents

COMPOSITIONS AND METHODS FOR THE TREATMENT OF SEVERE PAIN

The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of severe pain may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of postoperative pain, cancer pain, kidney stones pain, fractures, local pain, chronic pain, chemotherapy induced pain, neuropathic pain, post herpetic neuralgia, neuralgia, motor neurone disease, diabetic neuropathy, postherpetic neuralgia, injury, post-operative pain, osteoarthritis, rheumatoid arthritis, multiple sclerosis, spinal cord injury, migraine, HIV related neuropathic pain, cancer pain and lower back pain.

Opioids and efflux transporters. Part 3: P-glycoprotein substrate activity of 3-hydroxyl addition to meperidine analogs

Numerous studies have shown that many clinically employed opioid analgesics are substrates for P-glycoprotein (P-gp), suggesting that up-regulation of P-gp may contribute to the development of central tolerance to opioids. The studies herein focus on the development of SAR for P-gp substrate activity in the meperidine series of opioids. Addition of a 3-OH to meperidine and the ketone analog of meperidine yielding bemidone and ketobemidone, respectively, significantly increased P-gp substrate affinity. The results of this study have implications in the development of novel analgesics to be utilized as tools to study the contribution of P-gp on the development of central tolerance to opioids.

Some Spiro Analogues of the Potent Analgesic Ketobemidone

A series of spiro analogues of the potent narcotic ketobemidone have been prepared and found to be devoid of opiate activity.Additional pharmacology and possible implications for the mode of binding of ketobemidone to the analgesic receptor are discussed.