ガランタミン
(4aS,8aS)-3-メトキシ-11-メチル-4aα,5,9,10,11,12-ヘキサヒドロ-6H-ベンゾフロ[3a,3,2-ef][2]ベンゾアゼピン-6β-オール · ガランタミナ · (4aS,8aS)-4a,5,9,10,11,12-ヘキサヒドロ-3-メトキシ-11-メチル-6H-ベンゾフロ[3a,3,2-ef][2]ベンゾアゼピン-6β-オール · (-)-ガランタミン · (4S,6R,9S)-12-メチル-17-メトキシ-14,2-[1]プロペン[1]イル[3]イリデン-3-オキサ-12-アザトリシクロ[7.5.0.04,9]テトラデカン-1(14),7-ジエン-6-オール · ガランタミン · (8aS)-3-メトキシ-5,6,9,10,11,12-ヘキサヒドロ-11-メチル-4aαH-ベンゾフロ[3a,3,2-ef][2]ベンゾアゼピン-6β-オール · リコレミン
識別子と物理属性
| CAS No. | 357-70-0 |
|---|---|
| 分子式 | C17H21NO3 |
| 平均分子量 | 287.35 g/mol |
| 単同位体質量 | 287.15214353 g/mol |
| SMILES | COc1ccc2c3c1OC1CC(O)C=CC31CCN(C)C2 |
| InChIKey | ASUTZQLVASHGKV-UHFFFAOYSA-N |
| PubChem CID | 3449 |
| ChEMBL | CHEMBL1623394 |
| ChEBI | CHEBI:91735 |
| DTXSID | DTXSID70859345 |
| 現地名 | ガランタミン |
化学・物理的性質
| XLogP | 1.8 |
|---|---|
| 極性表面積 | 41.9 |
| 水素結合供与体数 | 1 |
| 水素結合受容体数 | 4 |
| 回転可能結合数 | 1 |
| 重原子数 | 21 |
| 形式電荷 | 0 |
| 複雑度 | 440 |
| 医薬品 | Pharmaceuticals |
| 融点 | 119-1210C |
| 比旋光度 | D20 -118.8° (c = 1.378 in ethanol) |
| 沸点 | 429.65°C (rough estimate) |
| 密度 | 1.0662 (rough estimate) |
| 屈折率 | 1.5022 (estimate) |
| 貯蔵条件 | Sealed in dry,Room Temperature |
| 溶解度 | ≥14.37 mg/mL in DMSO≥14.43 mg/mL in H2O with gentle warming≥45 mg/mL in EtOH with gentle warming |
| 外観・状態 | Powder |
| pKa（酸解離定数） | pKa 8.32 (Uncertain) |
| 色 | White to off-white |
| InChI | InChI=1S/C17H21NO3/c1-18-8-7-17-6-5-12(19)9-14(17)21-16-13(20-2)4-3-11(10-18)15(16)17/h3-6,12,14,19H,7-10H2,1-2H3/t12-,14-,17-/m0/s1 |
| InChIKey | ASUTZQLVASHGKV-JDFRZJQESA-N |
| SMILES | N1(C)CC2=CC=C(OC)C3O[C@]4([H])[C@@](C=C[C@H](O)C4)(C2=3)CC1 |
| CAS データベース | 357-70-0(CAS DataBase Reference) |
| NISTの化学物質情報 | Galantamin(357-70-0) |
化学的特性
Off-White Solid
安全性と法規制
| 毒性 | LD50 intraperitoneal in mouse: 10mg/kg |
|---|---|
| 有害物質データ | 357-70-0(Hazardous Substances Data) |
用途
解説
ガランタミン,無色の柱状晶．融点127～129 ℃．[α]20D－119°(エタノール)．抗コリンエステラーゼ作用を有し，臭化水素酸塩は小児麻ひの後遺症に有効である．森北出版「化学辞典（第2版）
用途
AChE阻害薬アルツハイマー型認知症治療薬。中枢性可逆的アセチルコリンエステラーゼ（AChE）阻害薬として実用化された。認知症状の改善作用をもつ。
説明
Galantamine is an Amaryllidaceae alkaloid which is first obtained from the plant of snowdrop (Galanthus nivalis), and nowadays, it’s extracted from the plants of Narcissus and Galanthus species or obtained from chemosynthesis. In many areas in Europe such as Bulgaria, eastern Turkey, and the Caucasus, the plants of Galanthus are native species. But its earliest pharmaceutical applications are seldom known. Plaitakis and Duvoisin hypothesized that “moly” in ancient Homer’s epic might be snowdrops. In Homer’s epic Odyssey, “moly” was used as an antidote by Odysseus against Circe’s poisonous drugs. To be used as an antidote may be the plants of Galanthus’ oldest medicinal records. But there is not much evidence for that. There is little evidence of the traditional application of the plants of Galanthus, and it is certain that until the Second World War, the plants of Galanthus and other genera of Amaryllidaceae were not frequently used in European drugsItalian scholar Iannello studied Pancratium illyricum L., an Amaryllidaceae species endemic to Sardinia, and isolated a new galantamine-type alkaloid in its leaves. This new galantamine-type compound exhibited a pronounced invitro AChE inhibitory activity (IC50 = 3.5±1.1 μM) in comparison with the reference standard galantamine hydrobromide (IC50=1.5±0.2μM)
天然物の起源
Galanthamine is a bulb plant found throughout the world.
来歴
In the early 1950s, Soviet Union’s scientists started modern medicine research of galantamine. In 1951, the Soviet Union’s pharmacologist Mashkovsky and Kruglikova-Lvova firstly proved its AChE-inhibiting properties, which was published in the paper. In 1957, the Bulgarian pharmacologist Paskov etal. found that the plants of Galanthus were the richest sources of galantamine, which opened a way for its commercial development by the company Sopharma in Bulgaria. Galantamine hydrobromide was launched into market under the trade name Nivalin. Initially, Nivalin was used in anesthesia to antagonize the effects of non-depolarizing muscle relaxants, and since then, it was rapidly introduced in other areas of medicineGalantamine hydrobromide was launched into market for the indication of mild to moderate Alzheimer’s disease firstly in 1995, developed by Sanochemia Pharmaceuticals. In the United States, galantamine hydrobromide was developed by Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, and was listed under the trade name Razadyne in 2001. So far, galantamine hydrobromide has been marketed in more than 20 countries and regions, such as the United States, Europe, and Japan.