10-(3-二甲基氨基-2-甲基丙基)-2-甲氧基吩噻嗪马来酸盐 | 7104-38-3

• 物质功能分类: 原料药 - 神经系统用药 - 抗精神病药
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 10-(3-二甲基氨基-2-甲基丙基)-2-甲氧基吩噻嗪马来酸盐
• 中文别名: 马来酸左美丙嗪；左美丙嗪马来酸盐
• 英文名称: Levomepromazine maleate
• 英文别名: methotrimeprazine maleate；methotrimeprazine maleate salt；Neuractil；(Z)-but-2-enedioic acid;(2R)-3-(2-methoxyphenothiazin-10-yl)-N,N,2-trimethylpropan-1-amine
• CAS: 7104-38-3
• 化学式: C₄H₄O₄*C₁₉H₂₄N₂OS
• 分子量: 444.552
• InChiKey: IFLZPECPTYCEBR-VIEYUMQNSA-N

物化性质

• 熔点：
  176-179°C
• 比旋光度：
  D20 -17° (c = 5 in chloroform)
• 溶解度：
  可溶于氯仿（少许）、DMF（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  4.21
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  8

安全信息

• 危险等级：
  6.1(b)
• 危险品运输编号：
  3249
• 包装等级：
  III
• 危险类别：
  6.1(b)
• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  10-(3-二甲基氨基-2-甲基丙基)-2-甲氧基吩噻嗪马来酸盐 在 盐酸 、 potassium nitrite 作用下， 以 水 、 丙酮 为溶剂， 反应 0.5h， 以0.4 g的产率得到
  参考文献：
  名称：

  The cytochrome P450-catalyzed metabolism of levomepromazine: a phenothiazine neuroleptic with a wide spectrum of clinical application

  摘要：

  The aim of the present study was to identify cytochrome P450 isoenzymes (CYPs) involved in the 5-sulfoxidation and N-demethylation of the aliphatic-type phenothiazine neuroleptic levomepromazine in human liver. Experiments were performed in vitro using cDNA-expressed human CYP isoforms (Supersomes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4), liver microsomes from different donors and CYP-selective inhibitors. The obtained results indicate that CYP3A4 is the main isoform responsible for levomepromazine 5-sulfoxidation (72%) and N-demethylation (78%) at a therapeutic concentration of the drug (10μM). CYP1A2 contributes to a lesser degree to levomepromazine 5-sulfoxidation (20%). The role of CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1 in catalyzing the above-mentioned reactions is negligible (0.1-8%). Moreover, at a higher, toxicological concentration of the neuroleptic (100μM), the relative contribution of CYP1A2 to levomepromazine metabolism visibly increases (from 20% to 28% for 5-sufoxidation, and from 8% to 32% for N-demethylation), while the role of CYP3A4 significantly decreases (from 72% to 59% for 5-sulfoxidation, and from 78% to 47% for N-demethylation). The obtained results indicate that the catalysis of levomepromazine 5-sulfoxidation and N-demethylation in humans shows a strict CYP3A4 preference, especially at a therapeutic drug concentration. Hence pharmacokinetic interactions involving levomepromazine and CYP3A4 substrates (e.g. tricyclic antidepressants, calcium channel antagonists, macrolide antibiotics, testosterone), inhibitors (e.g. ketoconazole, erythromycin, SSRIs) or inducers (e.g. rifampicin, carbamazepine) are likely to occur.

  DOI：

  10.1016/j.bcp.2014.05.005

文献信息

• Substituted 1,3-thiazole compounds, their production and use
  申请人：——

  公开号：US20040053973A1

  公开（公告）日：2004-03-18

  (1) A 1,3-thiazole compound of which the 5-position is substituted with a 4-pyridyl group having a substituent including no aromatic group or (2) a 1,3-thiazole compound of which the 5-position is substituted with a pyridyl group having at the position adjacent to a nitrogen atom of the pyridyl group a substituent including no aromatic group has an excellent p38 MAP kinase inhibitory activity.

  (1) 一种1,3-噻唑化合物，其5位被取代为含有一个取代基的4-吡啶基团，该取代基不包括芳香基，或者(2) 一种1,3-噻唑化合物，其5位被取代为一个吡啶基团，该吡啶基团的氮原子邻近位置有一个取代基，该取代基不包括芳香基，具有出色的p38 MAP激酶抑制活性。
• BENZAZEPINE DERIVATIVE, PROCESS FOR PRODUCING THE SAME, AND USE
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1422228A1

  公开（公告）日：2004-05-26

  The present invention provides a novel benzazepine derivative represented by formula : wherein, R1 is a 5- or 6-membered aromatic ring, R2 is lower alkyl group, etc., Y is an optionally substituted imino group, ring A and ring B are independently an optionally substituted aromatic ring, W is formula -W1-X2-W2- (W1 and W2 are independently S(O)m1 (m1 is 0, 1 or 2), etc., and X2 is an optionally substituted alkylene groupetc. ), a preparation method and use thereof.

  本发明提供了一种新型的苯并氮杂环衍生物，其由以下公式表示： 其中，R1是一个5-或6-成员的芳香环，R2是低级烷基团等，Y是可选地取代的亚氨基，环A和环B是独立地选自一个可选地取代的芳香环，W是公式-W1-X2-W2-（W1和W2是独立地为S(O)m1（m1是0、1或2）等，X2是一个可选地取代的亚烷基团等），其制备方法及其用途。
• [EN] HETEROCYCLIC COMPOUNDS AND THEIR USE AS RETINOID-RELATED ORPHAN RECEPTOR (ROR) GAMMA-T INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEUR UTILISATION EN TANT QU'INHIBITEURS GAMMA-T DU RÉCEPTEUR ORPHELIN APPARENTÉ AUX RÉCEPTEURS DES RÉTINOÏDES (ROR) )
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2016002968A1

  公开（公告）日：2016-01-07

  Provided are heterocyclic compounds having a RORγt inhibitory action represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

  提供的是具有RORγt抑制作用的杂环化合物，其由公式(I)表示：其中每个符号如说明书中定义，或其盐。
• MEDICINAL COMPOSITIONS
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1402900A1

  公开（公告）日：2004-03-31

  The present invention relates to an agent for the prophylaxis or treatment of pain, an agent for suppressing activation of osteoclast, and an inhibitor of osteoclast formation, which contains a p38 MAP kinase inhibitor and/or a TNF-α production inhibitor.

  本发明涉及一种用于预防或治疗疼痛的药剂，一种用于抑制破骨细胞活化的药剂，以及一种包含p38 MAP激酶抑制剂和/或TNF-α产生抑制剂的破骨细胞形成抑制剂。
• CONCOMITANT DRUGS
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1354603A1

  公开（公告）日：2003-10-22

  The present invention relates to a pharmaceutical agent containing one or more kinds of a p38 MAP kinase inhibitor and/or a TNF-α production inhibitor and one or more kinds of drugs selected from the group consisting of (1) a non-steroidal antiinflammatory drug, (2) a disease-modifying anti-rheumatic drug, (3) an anti-cytokine drug, (4) an immunomodulator, (5) a steroid and (6) a c-Jun N-terminal kinase inhibitor in combination. This combination agent is useful as a prophylactic or therapeutic agent of the diseases such as rheumatism, arthritis and the like, and other diseases.

  本发明涉及一种含有一种或多种p38 MAP激酶抑制剂和/或TNF-α产生抑制剂以及从（1）非甾体抗炎药、（2）疾病修饰性抗风湿药、（3）抗细胞因子药物、（4）免疫调节剂、（5）类固醇和（6）c-Jun N末端激酶抑制剂中选择的一种或多种药物的药物制剂。这种组合药剂可用作预防或治疗风湿病、关节炎等疾病以及其他疾病的药物。