那拉曲坦 | 121679-13-8

• 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: 那拉曲坦
• 中文别名: 纳拉曲坦；诺拉替坦；那拉曲坦; 纳拉曲坦
• 英文名称: naratriptan
• 英文别名: N-Methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethanesulphonamide；2-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]ethanesulfonic acid methylamide；N-methyl-2-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]ethanesulfonamide；[N-methyl-3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]ethanesulfonamide；N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethanesulfonamide
• CAS: 121679-13-8
• 化学式: C₁₇H₂₅N₃O₂S
• 分子量: 335.47
• InChiKey: AMKVXSZCKVJAGH-UHFFFAOYSA-N

物化性质

• 熔点：
  170-171°
• 沸点：
  541.3±60.0 °C(Predicted)
• 密度：
  1.227±0.06 g/cm3(Predicted)
• 物理描述：
  Solid
• 溶解度：
  35 mg/mL
• 碰撞截面：
  174.3 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)：
  2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  73.6
• 氢给体数：
  2
• 氢受体数：
  4

ADMET

代谢

主要在肝脏进行。在体外，纳拉曲坦通过广泛的细胞色素P450同工酶代谢，转化为多种无活性代谢物。

Primarily hepatic. <i>In vitro,</i> naratriptan is metabolized by a wide range of cytochrome P450 isoenzymes into a number of inactive metabolites.

来源:DrugBank

代谢

主要在肝脏进行。在体外，纳拉曲坦通过广泛的细胞色素P450同工酶代谢为多种无活性代谢物。 半衰期：5-8小时

Primarily hepatic. <i>In vitro,</i> naratriptan is metabolized by a wide range of cytochrome P450 isoenzymes into a number of inactive metabolites. Half Life: 5-8 hours

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

曲普坦类药物的三种不同药理作用被认为是其对偏头痛的治疗效果的原因：(1) 刺激突触前5-HT1D受体，这有助于抑制硬脑膜血管扩张和炎症；(2) 通过在大脑干中的5-HT1B/1D受体激动作用，直接抑制三叉神经核细胞的兴奋性；(3) 由于血管5-HT1B受体的激动作用，导致脑膜、硬脑膜、大脑或软脑膜血管的血管收缩。

Three distinct pharmacological actions have been implicated in the antimigraine effect of the triptans: (1) stimulation of presynaptic 5-HT1D receptors, which serves to inhibit both dural vasodilation and inflammation; (2) direct inhibition of trigeminal nuclei cell excitability via 5-HT1B/1D receptor agonism in the brainstem and (3) vasoconstriction of meningeal, dural, cerebral or pial vessels as a result of vascular 5-HT1B receptor agonism.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 药物性肝损伤

化合物：纳拉曲坦

Compound:naratriptan

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI标注：模糊的DILI关注

DILI Annotation:Ambiguous DILI-concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

严重等级：4

Severity Grade:4

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

不良反应部分

Label Section:Adverse reactions

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

吸收良好（74%口服生物利用度），吸收迅速，血浆浓度在2-5小时后达到峰值。在偏头痛发作期间，吸收速率较慢。

Well absorbed (74% oral biovaility), absorption is rapid with peak plasma concentrations after 2-5 hours. The rate of absorption is slower during a migraine attack.

来源:DrugBank

吸收、分配和排泄

• 分布容积

170升

170 L

来源:DrugBank

吸收、分配和排泄

• 清除

6.6毫升/分钟/千克

6.6 mL/min/kg

来源:DrugBank

安全信息

• 海关编码：
  2935009090
• 储存条件：
  2-8℃

制备方法与用途

生物活性：Naratriptan是5-HT1受体激动剂，可用于治疗偏头痛。

靶点：

• 5-HT₁受体

反应信息

• 作为反应物：
  描述：

  那拉曲坦 以79的产率得到盐酸那拉曲坦
  参考文献：
  名称：

  Indole derivatives

  摘要：

  公开了式(I)的化合物：##STR1## 其中R.sub.1代表H或C.sub.1-6烷基；R.sub.2代表H或C.sub.1-6烷基；R.sub.3代表H；R.sub.4代表H或C.sub.1-3烷基；以及药学上可接受的盐和溶剂（例如水合物）。这些化合物被指示为治疗偏头痛、群发性头痛、慢性阵发性半侧头痛和与血管疾病相关的头痛的有用药物。还公开了它们的制备过程和中间体以及含有它们的制药组合物。

  公开号：

  US04997841A1
• 作为产物：
  描述：

  盐酸那拉曲坦 在 sodium hydroxide 作用下， 以 水 为溶剂， 生成 那拉曲坦
  参考文献：
  名称：

  Preparation, characterization and buccal permeation of naratriptan

  摘要：

  Naratriptan (NAR) is currently used for the management of migraine as the hydrochloride salt (NAR.HCl) and is administered as an oral tablet. This work evaluates the feasibility of buccal delivery of NAR in order to ensure faster onset of action and avoid the side-effects associated with conventional oral formulations. We hypothesized that the unionized form of NAR would permeate buccal tissue to a greater extent than the salt. Therefore the first stage of this work required preparation of the free base from NAR.HCl. Characterisation of the base with thermal and elemental analyses confirmed its purity; log P and log D values were also determined. The pH permeation profile of NAR was also determined in the range 7.4-10. Solubility studies in non-aqueous solvents indicated that Transcutol (TM) (TC) and dipropylene glycol (DPG) were suitable vehicles for the free base. Maximum amounts of NAR which permeated after 6 h were similar to 130 mu g/cm(2). Based on the pH permeation results and studies conducted at two different doses NAR appears to permeate porcine buccal tissue via the transcellular route. Finally, estimates of likely systemic values suggest that optimised formulations should be taken forward for in vivo evaluation. (C) 2015 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ijpharm.2015.07.035

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] COMPOUNDS THAT MODULATE EGFR ACTIVITY AND METHODS FOR TREATING OR PREVENTING CONDITIONS THEREWITH<br/>[FR] COMPOSÉS MODULANT L'ACTIVITÉ DES RÉCEPTEURS EGFR ET MÉTHODES POUR TRAITER OU PRÉVENIR DES TROUBLES À L'AIDE DE CEUX-CI
  申请人：GATEKEEPER PHARMACEUTICALS INC

  公开号：WO2011140338A1

  公开（公告）日：2011-11-10

  Provided are compounds and methods for treating or preventing kinase-mediated disorders therewith.

  提供了用于治疗或预防激酶介导的疾病的化合物和方法。
• [EN] NAPHTHALENE CARBOXAMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] COMPOSÉS DE NAPHTHALÈNE CARBOXAMIDE, MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1
  申请人：MERCK SHARP & DOHME

  公开号：WO2011149801A1

  公开（公告）日：2011-12-01

  The present invention is directed to naphthalene carboxamide compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimers disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的萘甲酰胺化合物，它们是M1受体阳性变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。该发明还涉及包含这些化合物的药物组合物，以及在治疗由M1受体介导的疾病中使用这些化合物和组合物。
• [EN] KINASE INHIBITORS FOR THE TREATMENT OF DISEASE<br/>[FR] INHIBITEURS DE KINASE POUR LE TRAITEMENT D'UNE MALADIE
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2015006492A1

  公开（公告）日：2015-01-15

  The invention relates to compounds and their use in the treatment of disease. Novel irreversible inhibitors of wild-type and mutant forms of EGFR, FGFR, ALK, ROS, JAK, BTK, BLK, ITK, TEC, and/or TXK and their use for the treatment of cell proliferation disorders are described.

  这项发明涉及化合物及其在治疗疾病中的应用。描述了用于治疗细胞增殖紊乱的新型EGFR、FGFR、ALK、ROS、JAK、BTK、BLK、ITK、TEC和/或TXK的野生型和突变型不可逆抑制剂及其应用。
• [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。

表征谱图