阿莫曲普坦 | 154323-57-6

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 阿莫曲普坦
• 中文别名: N,N-二甲基-2-(5-((吡咯烷-1-基磺酰基)甲基)-1H-吲哚-3-基)乙胺；阿莫曲坦；3-(2-二甲胺乙基)-5-(1-吡咯烷基磺酰甲基)-1H-吲哚
• 英文名称: almotriptan
• 英文别名: N,N-dimethyl-2-(5-((pyrrolidin-1-ylsulfonyl)methyl)-1Hindol-3-yl)ethan-1-amine；N,N-dimethyl-2-[5-(pyrrolidin-1-ylsulfonyl-methyl)-1H-indol-3-yl]-ethanamine；N,N-dimethyl-2-[5-(pyrrolidin-1-ylsulfonylmethyl)-1H-indol-3-yl]ethanamine；3-[2-(dimethylamino)ethyl]-5-(pyrrolidin-1-ylsulfonylmethyl)-1H-indole；3-[(2-dimethylamino)ethyl]-5-(1-pyrrolidinylsulfonylmethyl)indole
• CAS: 154323-57-6
• 化学式: C₁₇H₂₅N₃O₂S
• 分子量: 335.47
• InChiKey: WKEMJKQOLOHJLZ-UHFFFAOYSA-N

物化性质

• 沸点：
  538.7±60.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)
• 物理描述：
  Solid
• 溶解度：
  1.21e-01 g/L
• 碰撞截面：
  175.8 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  64.8
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

almotriptan已知的人体代谢物包括甲基(2-{5-[(吡咯烷-1-磺酰基)甲基]-1H-吲哚-3-基}乙基)胺和2-羟基-almotriptan。

Almotriptan has known human metabolites that include methyl(2-{5-[(pyrrolidine-1-sulfonyl)methyl]-1H-indol-3-yl}ethyl)amine and 2-hydroxy-almotriptan.

来源:NORMAN Suspect List Exchange

代谢

肝脏。 消除途径：阿莫曲普坦主要通过肾脏排泄（约口服剂量的75%），约40%的给药剂量以原形从尿液中排出。大约13%的给药剂量通过粪便排出，包括未改变和代谢后的。

Hepatic. Route of Elimination: Almotriptan is eliminated primarily by renal excretion (about 75% of the oral dose), with approximately 40% of an administered dose excreted unchanged in urine. Approximately 13% of the administered dose is excreted via feces, both unchanged and metabolized. Half Life: 3-4 hours

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

阿莫曲坦与人类5-HT1B和5-HT1D受体具有高亲和力，导致颅脑血管收缩。

Almotriptan binds with high affinity to human 5-HT_1B and 5-HT_1D receptors leading to cranial blood vessel constriction.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 药物性肝损伤

药物：阿莫曲坦

Compound:almotriptan

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注释：无 DILI（药物性肝损伤）担忧

DILI Annotation:No-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

标签部分：无匹配

Label Section:No match

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 美国食品药品监督管理局批准的药物标签用于研究药物诱导的肝损伤，《药物发现今日》，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按人类发展药物诱导肝损伤风险排名的最大参考药物清单。《药物发现今日》2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 消除途径

阿莫曲坦主要通过肾脏排泄（约占总口服剂量的75%），大约40%的给药剂量以原型药物形式在尿液中排出。大约13%的给药剂量通过粪便排出，包括未改变的和代谢后的形式。

Almotriptan is eliminated primarily by renal excretion (about 75% of the oral dose), with approximately 40% of an administered dose excreted unchanged in urine. Approximately 13% of the administered dose is excreted via feces, both unchanged and metabolized.

来源:DrugBank

吸收、分配和排泄

• 分布容积

180到200升

180 to 200 L

来源:DrugBank

吸收、分配和排泄

• 清除

57 L/h [健康] 34.2 L/h [中度肾功能损害（肌酐清除率在31至71 mL/min之间）] 9.8 L/h [严重肾功能损害（肌酐清除率在10至30 mL/min之间）]

57 L/h [healthy] 34.2 L/h [moderate renal impairment (creatinine clearance between 31 and 71 mL/min)] 9.8 L/h [severe renal impairment (creatinine clearance between 10 and 30 mL/min)]

来源:DrugBank

安全信息

• 海关编码：
  2935009090
• 储存条件：
  | 室温 |

制备方法与用途

生物活性方面，阿尔莫特里班（Almotriptan）是一种5-HT1B/1D受体激动剂，用于研究偏头痛。

靶点包括：

• 5-HT_1B 受体
• 5-HT_1D 受体

反应信息

• 作为反应物：
  描述：

  阿莫曲普坦 在 丁二酸 作用下， 以 乙酸乙酯 为溶剂， 反应 15.0h， 生成 almotriptan succinate
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF 1-[[[3-[2-(DIMETHYLAMINO)ETHYL]-1H-INDOL-5-YL]METHYL]SULFONYL] PYRROLIDINE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
  [FR] PROCEDE DE PREPARATION DE 1-[[[3-[2-(DIMETHYLAMINO)ETHYL]-1H-INDOL-5-YL]METHYL]SULFONYL]PYRROLIDINE ET DE SES SELS PHARMACEUTIQUEMENT ACCEPTABLES

  摘要：

  公开号：

  WO2010113183A3
• 作为产物：
  描述：

  almotriptan succinate 在 氨 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 0.5h， 生成 阿莫曲普坦
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF 1-[[[3-[2-(DIMETHYLAMINO)ETHYL]-1H-INDOL-5-YL]METHYL]SULFONYL] PYRROLIDINE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
  [FR] PROCEDE DE PREPARATION DE 1-[[[3-[2-(DIMETHYLAMINO)ETHYL]-1H-INDOL-5-YL]METHYL]SULFONYL]PYRROLIDINE ET DE SES SELS PHARMACEUTIQUEMENT ACCEPTABLES

  摘要：

  公开号：

  WO2010113183A3

文献信息

• [EN] COMPOUNDS AND THEIR USE AS BACE INHIBITORS<br/>[FR] COMPOSÉS ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE BACE
  申请人：ASTRAZENECA AB

  公开号：WO2016055858A1

  公开（公告）日：2016-04-14

  The present application relates to compounds of formula (I), (la), or (lb) and their pharmaceutical compositions/preparations. This application further relates to methods of treating or preventing Αβ-related pathologies such as Down's syndrome, β- amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia, including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease.

  本申请涉及式(I)、(Ia)或(Ib)的化合物及其药物组合物/制剂。本申请进一步涉及治疗或预防与Αβ相关的病理学，如唐氏综合症，β-淀粉样蛋白血管病，如但不限于脑淀粉样蛋白血管病或遗传性脑出血，与认知损害相关的疾病，如但不限于MCI（“轻度认知损害”），阿尔茨海默病，记忆丧失，与阿尔茨海默病相关的注意力缺陷症状，与疾病如阿尔茨海默病或痴呆症相关的神经退行性疾病，包括混合性血管性和退行性起源的痴呆，早老性痴呆，老年性痴呆和与帕金森病相关的痴呆的方法。
• [EN] QUINAZOLINE DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO<br/>[FR] DÉRIVÉS DE QUINAZOLINE, COMPOSITIONS ET UTILISATIONS ASSOCIÉES
  申请人：UNIV EMORY

  公开号：WO2013181135A1

  公开（公告）日：2013-12-05

  The disclosure relates to quinazoline derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to inhibitors of NADPH-oxidases (Nox enzymes) and/or myeloperoxidase.

  该披露涉及喹唑啉衍生物、组合物以及相关方法。在某些实施例中，该披露涉及NADPH-氧化酶（Nox酶）和/或髓过氧化物酶的抑制剂。
• [EN] SPIROLACTAM CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR DE CGRP À BASE DE SPIROLACTAME
  申请人：MERCK SHARP & DOHME

  公开号：WO2013169567A1

  公开（公告）日：2013-11-14

  The present invention is directed to spirolactam analogues which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及螺内酰胺类似物，其为CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的这类疾病中使用这些化合物和组合物。
• [EN] PYRROLE COMPOUNDS FOR THE TREATMENT OF PROSTAGLANDIN MEDIATED DISEASES<br/>[FR] COMPOSES PYRROLIQUES DESTINES AU TRAITEMENT DE MALADIES INDUITES PAR PROSTAGLANDINE
  申请人：GLAXO GROUP LTD

  公开号：WO2003101959A1

  公开（公告）日：2003-12-11

  Compounds of formula (I) or a pharmaceutically acceptable derivative thereof: wherein A, R1, R2a, R2b, Rx, R8, and R9 are as defined in the specification, a process for the preparation of such compounds, pharmaceutical compositions comprising such compounds and the use of such compounds in medicine, in particular their use in the treatment of prostaglandin mediated diseases such as pain, inflammatory, immunological, bone, neurodegenerative or renal disorder.

  式(I)的化合物或其药学上可接受的衍生物：其中A、R1、R2a、R2b、Rx、R8和R9如规范中所定义，一种制备这种化合物的方法，包括这种化合物的药物组合物以及这种化合物在医学中的用途，特别是它们在治疗前列腺素介导的疾病，如疼痛、炎症、免疫、骨骼、神经退行性或肾脏疾病中的用途。
• [EN] INDANE DERIVATIVES AS MGLUR7 MODULATORS<br/>[FR] DÉRIVÉS D'INDANE UTILISÉS COMME MODULATEURS DE MGLUR7
  申请人：TAKEDA PHARMACEUTICALS CO

  公开号：WO2017131221A1

  公开（公告）日：2017-08-03

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4a and R4b are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy. The compounds of formula (I) are mGluR7 modulators.

  本发明提供了式（I）的化合物及其药学上可接受的盐，其中R1、R2、R3、R4a和R4b如规范中定义，其制备方法，含有它们的药物组合物以及它们在治疗中的用途。式（I）的化合物是mGluR7调节剂。