ラメルテオン

ラメルテオン 化学構造式
196597-26-9
CAS番号.
196597-26-9
化学名:
ラメルテオン
别名:
ラメルテオン;ラメルテオン (JAN);N-[2-[(S)-1,6,7,8-テトラヒドロ-2H-インデノ[5,4-b]フラン-8-イル]エチル]プロピオンアミド;ロゼレム;N-[2-[(S)-2,6,7,8-テトラヒドロ-1H-インデノ[5,4-b]フラン-8β-イル]エチル]プロピオンアミド;N-{2-[(8S)-1H,2H,6H,7H,8H-インデノ[5,4-b]フラン-8-イル]エチル}プロパンアミド;(S)-N-[2-(1,6,7,8-テトラヒドロ-2H-インデノ[5,4-b]フラン-8-イル)エチル]プロピオンアミド
英語名:
Ramelteon
英語别名:
Rozerem;(S)-N-(2-(2,6,7,8-tetrahydro-1H-indeno[5,4-b]furan-8-yl)ethyl)propionamide;N-[2-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl]propanamide;DF883;TAK-375;CS-1962;RAMELTEON;Rhodialux;rac Rozerem;Rametylamine
CBNumber:
CB0496858
化学式:
C16H21NO2
分子量:
259.34
MOL File:
196597-26-9.mol
MSDS File:
SDS

ラメルテオン 物理性質

融点 :
113-1150C
比旋光度 :
D20 -57.8° (c = 1.004 in chloroform)
沸点 :
455.3±24.0 °C(Predicted)
比重(密度) :
1.119±0.06 g/cm3(Predicted)
闪点 :
2℃
貯蔵温度 :
Sealed in dry,Store in freezer, under -20°C
溶解性:
ジメチルスルホキシド、エタノール、メタノール、
外見 :
個体
酸解離定数(Pka):
16.37±0.46(Predicted)
色:
結晶性
InChI:
InChI=1S/C16H21NO2/c1-2-15(18)17-9-7-12-4-3-11-5-6-14-13(16(11)12)8-10-19-14/h5-6,12H,2-4,7-10H2,1H3,(H,17,18)/t12-/m0/s1
InChIKey:
YLXDSYKOBKBWJQ-LBPRGKRZSA-N
SMILES:
C(NCC[C@H]1C2=C3CCOC3=CC=C2CC1)(=O)CC
CAS データベース:
196597-26-9(CAS DataBase Reference)
安全性情報
  • リスクと安全性に関する声明
  • 危険有害性情報のコード(GHS)
主な危険性  F,Xn
Rフレーズ  11-20/21/22-36
Sフレーズ  16-36/37
RIDADR  UN 1648 3 / PGII
WGK Germany  2
HSコード  2932.99.7000
有毒物質データの 196597-26-9(Hazardous Substances Data)
絵表示(GHS) GHS hazard pictograms
注意喚起語 警告
危険有害性情報
コード 危険有害性情報 危険有害性クラス 区分 注意喚起語 シンボル P コード
H302 飲み込むと有害 急性毒性、経口 4 警告 GHS hazard pictograms P264, P270, P301+P312, P330, P501
注意書き

ラメルテオン 価格 もっと(7)

メーカー 製品番号 製品説明 CAS番号 包装 価格 更新時間 購入
富士フイルム和光純薬株式会社(wako) W01W0118-0337 ラメルテオン 98.0+% (HPLC)
Ramelteon 98.0+% (HPLC)
196597-26-9 100mg ¥15000 2024-03-01 購入
富士フイルム和光純薬株式会社(wako) W01W0118-0337 ラメルテオン 98.0+% (HPLC)
Ramelteon 98.0+% (HPLC)
196597-26-9 500mg ¥60000 2024-03-01 購入
東京化成工業 R0216 ラメルテオン >98.0%(GC)
Ramelteon >98.0%(GC)
196597-26-9 100mg ¥11900 2023-06-01 購入
東京化成工業 R0216 ラメルテオン >98.0%(GC)
Ramelteon >98.0%(GC)
196597-26-9 1g ¥74000 2023-06-01 購入
Sigma-Aldrich Japan SML2262
Ramelteon
196597-26-9 10MG ¥25400 2024-03-01 購入

ラメルテオン 化学特性,用途語,生産方法

外観

白色~うすい黄色、結晶性粉末~粉末

効能

催眠薬, メラトニン受容体作動薬

商品名

ロゼレム (武田薬品工業)

説明

Ramelteon, also known as N-[2-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl]propanamide, is a melatonin agonist developed by Takeda Pharmaceuticals, Inc. It was approved by the FDA for marketing in the United States in September 2005 and is marketed under the name Rozerem. It is used to treat difficult-to-sleep and short-term insomnia. Ramelteon is effective for both chronic and short-term insomnia. Unlike most treatments of insomnia that target the GABA (g-aminobutyric acid) receptor complex, ramelteon is an agonist of the melatonin receptor. In particular, it has high selectivity for the MT1 and MT2 subtypes, which have been implicated in the maintenance of circadian rhythms, over the MT3 receptor responsible for other melatonin functions. Its lack of affinity for not only the GABA receptor complex but also neurotransmitter, dopaminerigic, opiate, and benzodiazepine receptors suggests an improved safety profile devoid of the abuse potential of the hypnotic drugs that target these receptors. As such, ramelteon is not a scheduled drug.

化学的特性

Crystalline Solid

使用

Ramelteon is a selective melatonin receptor agonist of MT1 and MT2 approved for the treatment of insomnia (trouble in sleeping). It acts as a sedative and hypnotic agent. Ramelteon is the only prescription sleep aid not designated as a Schedule IV controlled substance.

一般的な説明

The melatonin molecule was modified mainly by replacing the nitrogen of the indole ring with a carbon to give an indane ring and by incorporating 5-methoxyl group in the indole ring into a more rigid furan ring. The selectivity of the resulting ramelteon for MT1 receptor is eight times more than that of MT2 receptor. Unlike melatonin, it is more effective in initiating sleep (MT1 activity) rather than to readjust the circadian rhythm (MT2 activity). It appears to be distinctly more efficacious than melatonin but less efficacious than benzodiazepines as a hypnotic. Importantly, this drug has no addiction liability (it is not a controlled substance). As a result, it has recently been approved for the treatment of insomnia.

合成

Vilsmeier-Haack reaction on benzofuran 112 provided aldehyde 113 (100%), which was converted to olefin 114 (88%) by Horner-Emmons reaction with triethylphosphonoacetate, and was followed by hydrogenation of the olefin to give ester 115 (100%). In order to avoid the cyclization of the acid chloride intermediate into the wrong position, the benzene ring was protected by bromination. Both bromination and hydrolysis of the ester is accomplished in a single pot to give acid 116. Thus the ester is brominated with bromine in sodium acetate and acetic acid at 0°C and RT for several hours followed by quenching of remaining bromide by sodium thiosulfate. The resulting acidic solution was taken up in acetonitrile and refluxed for 2hr to provide the acid 116 in 73% yield. The conversion of the acid to acid chloride was done by reacting with thionyl chloride in odichlorobenzene at 40°C for 30 to 40 min after which the reaction was cooled to 0°C . Aluminum trichloride was added and the reaction mixture was stirred at 0°C for 30 min to deliver cyclized ketone 117 in 92% yield. After completion of the cyclization, the bromines are removed by hydrogenation (86%) and resulting ketone 118 was then reacted under Horner-Emmons condition with diethyl cyano phosphonate to give vinyl nitrile 119 in 84% yield. Selective reduction of the nitrile was accomplished by hydrogenation under basic condition (sodium hydroxide in toluene) in the presence of the activated cobalt at 25-50°C for 6.5 hr. The amine was recovered as hydrochloride salt 120 (99% yield) by treating the amine with HCl in methanol. In the next step, the amine salt 120 was taken up in toluene and treated with sodium hydroxide followed by hydrogenation of the mixture with [RuCl(benzene)(R)-BINAP]Cl as catalyst to provide chiral amine 121, after several work up and palladium catalyzed hydrogenations, in 73% overall yield. Final acylation of the amine with propionyl chloride in the presence of aqueous sodium hydroxide in THF at room temperature gave the desired product ramelteon (XVI), after crystallization, in 97% yield.
説明図

参考文献

[1] KATOKOKI. Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist.[J]. Neuropharmacology, 2005. DOI:10.1016/j.neuropharm.2004.09.007.
[2] MIYAMOTO M. Pharmacology of Ramelteon, a Selective MT1/MT2 Receptor Agonist: A Novel Therapeutic Drug for Sleep Disorders[J]. CNS Neuroscience & Therapeutics, 2009. DOI:10.1111/j.1755-5949.2008.00066.x.
[3] MCGECHANADAM  WellingtonKeri. Ramelteon.[J]. CNS drugs, 2005. DOI:10.2165/00023210-200519120-00007.
[4] BORJANANCY L   DanielKaren L. Ramelteon for the treatment of insomnia.[J]. Clinical therapeutics, 2006. DOI:10.1016/j.clinthera.2006.10.016.

ラメルテオン 上流と下流の製品情報

原材料

準備製品


ラメルテオン 生産企業

Global( 394)Suppliers
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ATK CHEMICAL COMPANY LIMITED
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sales@coreychem.com China 29914 58

ラメルテオン  スペクトルデータ(1HNMR)


196597-26-9(ラメルテオン)キーワード:


  • 196597-26-9
  • rac N-[-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl]propanamide
  • rac Ramelteon
  • rac Rozerem
  • TAK-375
  • RAMELTEON(FORR&DONLY)
  • (S)-N-[2-(1,6,7,8-Tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide
  • N-[-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-β]furan-8-yl]ethyl]propanamide
  • Ramelteon (approx. 90% S)
  • RAMELTEON
  • rac N-[-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-β]furan-8-yl]ethyl]propanamide
  • N-[-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl]propanamide
  • rac Ramelteon DISCONTINUED. See R110051
  • RaMelteon(TAK-375)
  • N-(2-(2,6,7,8-tetrahydro-1H-indeno[5,4-b]furan-8-yl)ethyl)propionaMide
  • RaMelteon,(S)-N-[2-(1,6,7,8-Tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionaMide
  • Ramelteon solution
  • Ramelteon, >=99%
  • CS-1962
  • TAK-375; ROZEREM; TAK375; TAK 375;
  • N-[2-[(8S)-2,6,7,8-tetrahydro-1H-cyclopenta[e][1]benzofuran-8-yl]ethyl]propanamide
  • UNII-901AS54I69
  • Propanamide, N-[2-[(8S)-1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl]-
  • Ramelteon USP/EP/BP
  • DF883
  • RamelteonQ: What is Ramelteon Q: What is the CAS Number of Ramelteon Q: What is the storage condition of Ramelteon Q: What are the applications of Ramelteon
  • P Sanduvor 3035
  • Rhodialux
  • Rozerem
  • (S)-N-(2-(2,6,7,8-tetrahydro-1H-indeno[5,4-b]furan-8-yl)ethyl)propionamide
  • N-[2-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl]propanamide
  • ラメルテオン
  • ラメルテオン (JAN)
  • N-[2-[(S)-1,6,7,8-テトラヒドロ-2H-インデノ[5,4-b]フラン-8-イル]エチル]プロピオンアミド
  • ロゼレム
  • N-[2-[(S)-2,6,7,8-テトラヒドロ-1H-インデノ[5,4-b]フラン-8β-イル]エチル]プロピオンアミド
  • N-{2-[(8S)-1H,2H,6H,7H,8H-インデノ[5,4-b]フラン-8-イル]エチル}プロパンアミド
  • (S)-N-[2-(1,6,7,8-テトラヒドロ-2H-インデノ[5,4-b]フラン-8-イル)エチル]プロピオンアミド
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