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| 化学名: | ペルゴリド·メタンスルホン酸 | | 英語化学名: | Pergolide mesylate salt | | 别名: | 8BETA-[(METHYLTHIO)METHYL]-6-PROPYLERGOLINE MESYLATE SALT;8-BETA-[(METHYLTHIO)METHYL]-6-PROPYLERGOLINE MONOMETHANE SULFONATE;Pergolide mesylate EPIV;Pergolidemetylsulfonate;(8b)-8-[(Methylthio)methyl]-6-propylergoline Mesylate;Celance;Nopar;Permax | | CAS番号: | 66104-23-2 | | 分子式: | C20H30N2O3S2 | | 分子量: | 410.59 | | EINECS: | | | カテゴリ情報: | LOCOID;API;Intermediates & Fine Chemicals;Neurochemicals;Pharmaceuticals | | Mol File: | 66104-23-2.mol |  |
| 融点 | 252-254°C | | 比旋光度 | aD20 between -18.0° and -23.0° (c = 10 mg/ml in DMF) | | 貯蔵温度 | Inert atmosphere,Store in freezer, under -20°C | | 溶解性 | ethanol: soluble2mg/mL | | 酸解離定数(Pka) | pKa (66% DMF) 7.8(at 25℃) | | 外見 | solid | | 色 | white | | 光学活性 (optical activity) | [α]20/D 35°, c = 0.2 in pyridine(lit.) | | InChIKey | UWCVGPLTGZWHGS-PLBOZXOQNA-N | | SMILES | C12=C3C=CC=C1[C@@]1([H])C[C@H](CN(CCC)[C@]1([H])CC2=CN3)CSC.S(=O)(=O)(O)C |&1:6,9,15,r| | | CAS データベース | 66104-23-2(CAS DataBase Reference) |
| 主な危険性 | T+ | | Rフレーズ | 28 | | Sフレーズ | 28-36/37-45 | | RIDADR | UN 1544 | | WGK Germany | 3 | | RTECS 番号 | KE6345000 | | HSコード | 2939690000 |
| | ペルゴリド·メタンスルホン酸 Usage And Synthesis |
| 用途 | ドーパミンD2 受容体に作用し、
ドーパミン作動作用を示します。 | | 用途 | ドパミンD2 受容体に作用し、 ドパミン作動作用を示します。 | | 効能 | パーキンソン病治療薬, ドパミン受容体作動薬 | | 商品名 | ペルマックス (協和発酵キリン) | | 説明 | Pergolide mesylate is a potent, long-acting dopamine agonist useful in the treatment of
Parkinson’s disease and hyperprolactinemia, Compared with lergotrile, pergolide mesylate
has shown less toxicity and lower propensity for inducing psychosis. | | 説明 | Pergolide is a potent dopamine D1 and D2 receptor agonist (Kis = 111 and 0.495 nM, respectively, for rat striatal receptors). It depresses dopaminergic firing in paralyzed rats (ED50 = <20 μg/kg), an effect that can be reversed by the dopamine D2-selective antagonist spiperone or the dopamine D1-selective antagonist SCH 23390 . Pergolide (0.025 and 0.05 mg/kg) increases the volume threshold for inducing bladder contraction in a cynomolgus monkey model of Parkinson''s disease induced by MPTP. It also reduces carrageenan-induced paw edema in adrenalectomized rats (ED50 = 0.4 mg/kg). | | 化学的特性 | White to Off-White Solid | | Originator | Lilly (USA) | | 使用 | dopamine receptor agonist, anti-Parkinson's agent | | 使用 | glucocorticoid, antiinflammatory | | 使用 | A dopaminergic agonist that also decrease plasma prolactin concentrations. An antiparkinsonian agent | | 定義 | ChEBI: A methanesulfonate salt obtained from pergolide by mixing eqimolar amount of pergolide and methanesulfonic acid. A dopamine D2 receptor agonist which also has D1 and D2 agonist properties, it i
used in the management of Parkinson's disease, although it was withdrawn from the U.S. and Canadian markets in 2007 due to an increased risk of cardiac valve dysfunction. | | Manufacturing Process | Dimethyl disulfide (73.6 ml, 0.79 mol) and tri-n-butylphosphine (79.6 ml, 0.32 mol) were added to a solution of 9,10-dihydrolysergol in (8.1 g, 0.032 mol) in the 150 ml of anhydrous DMF and were stirred at room temperature for 6 hours under a nitrogen atmosphere. Dimethyl disulfide of the reaction mixture was removed under vacuo. A solution of the residue in ethyl acetate was extracted with 3.7% HCl (aq.). The aqueous layer was basified with ammonium hydroxide to a pH of 10 and then extracted with ethyl acetate. Removal of ethyl acetate followed by a silica gel column purification eluting with 10% MeOH/CH2Cl2 gave5.5.g of D-6-methyl-8β(methylthiomethyl)ergoline (60%).
A solution of D-6-methyl-8β-(methylthiomethyl)ergoline (0.4 g, 0.0014 mol) and NaI (0.63 g, 0.0042 mol) in 10 ml of propionic anhydride was refluxed for 40 hours. The reaction mixture was guenched with a 10% Na2CO3 solution and extracted by ethyl acetate. The combined organic layers were washed with a saturated brine solution, dried with magnesium sulfate and concentrated to produce oil. The oil was purified by silica gel column, eluting with 10% MeOH/CH2Cl2 to give 0.33 g of D-1,6-dipropionyl-8β(methylthiomethyl)ergoline.
LiAlH4 (0.6 g, 0.0156 mol) was slowly added to a solution of D-1,6dipropionyl-8β-(methylthiomethyl)ergoline in the 20 ml anhydrous THF at 0°C under nitrogene atmosphere. The mixture was stirred at 0°C for 30 min and then at room temperature for 4 hours. The reaction was cooled to 0°C and 0.6 ml of water was slowly added. The mixture was stirred at 0°C for 10 min and 1.8 ml of 15% NaOH (aq.) and 2.5 ml of water were added respectively. The mixture was stirred for 30 min at room temperature and then filtered. Excess of the solvent was removed under reduced pressure to give 150 mg of 8β-((methylthio)methyl)-6-propyl-ergoline or pergolide (yield: 68%). Ergoline,8-((methylthio)methyl)-6-propyl-, monomethanesulfonate, (8β)- may be prepared by mixing of components in solution. | | brand name | Permax (Valeant). | | Therapeutic Function | Dopamine agonist | | Biochem/physiol Actions | Dopaminergic agonist; suppresses pituitary secretion of prolactin; anti-Parkinsonian agent. |
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