莫西赛利 | 54-32-0

• 物质功能分类: 原料药 - 神经系统用药 - 脑代谢调节药
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 莫西赛利
• 中文别名: 百里胺；MOXISYLYTE盐酸盐
• 英文名称: thymoxamine
• 英文别名: Moxisylyte；carlytene；[2-(4-acetoxy-2-isopropyl-5-methyl-phenoxy)-ethyl]-dimethyl-amine；[2-(4-Acetoxy-2-isopropyl-5-methyl-phenoxy)-aethyl]-dimethyl-amin；[4-[2-(dimethylamino)ethoxy]-2-methyl-5-propan-2-ylphenyl] acetate
• CAS: 54-32-0
• 化学式: C₁₆H₂₅NO₃
• 分子量: 279.379
• InChiKey: VRYMTAVOXVTQEF-UHFFFAOYSA-N

物化性质

• 沸点：
  371ºC at 760 mmHg
• 熔点：
  145ºC
• 溶解度：
  >47.4 ug/ml

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

甲氧基锡的药代动力学特性使其被认为是一种前药，因为它的生物转化非常迅速。这种药物在血浆和组织中被伪胆碱酯酶迅速水解，产生主要代谢物去乙酰氧基-甲氧基胺。这个初级代谢物随后被细胞色素P450单加氧酶系统去甲基化，形成去乙酰-去甲基-甲氧基胺。这两个主要代谢物都具有药理活性。尿和粪便中甲氧基锡的药代动力学研究显示存在8种不同的代谢物，其中两种极性很高，对酶促水解有抵抗力。从这些代谢物中，已经检测到了主要代谢物的硫酸盐和葡萄糖苷酸共轭物。

The pharmacokinetic profile of moxisylyte can make this drug to be considered as a prodrug as its biotransformation is very rapid. This drug gets rapidly hydrolyzed by pseudocholinesterase in plasma and tissues to give the major metabolite deacetyl-thymoxamine. This first metabolite is later demethylated by the cytochrome P450 monooxygenase system to form deacetyl-demethyl-thymoxamine. Both of this major metabolites are pharmacologically active. The pharmacokinetic studies with moxisylyte in urine and feces have shown the presence of 8 different metabolites, where two of them are highly polar and resistant to enzymatic hydrolysis. From this metabolites, it has been detected the sulfate and glucuronide conjugates of the major metabolites.

来源:DrugBank

毒理性

• 药物性肝损伤

化合物：莫西沙星

Compound:moxisylyte

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注解：最令人关注的药物性肝损伤

DILI Annotation:Most-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

严重等级：8

Severity Grade:8

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

已撤回

Label Section:Withdrawn

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. 用于研究药物诱导肝损伤的FDA批准药物标签，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：按在人体内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

• 吸收

Moxisylyte口服给药后迅速吸收。在其剂量范围内，从10到30毫克的Cmax和AUC值的药代动力学特征呈线性。静脉给药后，最大血浆浓度为352.8纳克/毫升，AUC为152.6微克·小时/升。在临床前试验中，生物利用度始终大约为10%。

Moxisylyte is rapidly absorbed after oral administration. Its pharmacokinetic profile is linear in the dose range from 10 to 30 mg for the values of Cmax and AUC. After intravenous administration, the maximal plasma concentration was of 352.8 ng/ml with an AUC of 152.6 mcg h/L. In preclinical trials, the bioavailability was always presented in approximately 10%.

来源:DrugBank

吸收、分配和排泄

• 消除途径

Moxisylyte的主要消除途径是通过肾脏。当静脉给药时，所有代谢物通过尿液完全排出的比例为75%，口服给药时为69%。从消除曲线来看，Moxisylyte的两个主要代谢物在尿液中的特定范围分别是：脱乙酰硫氧胺为50%，N-单去甲基脱乙酰硫氧胺为10%。通过粪便排出的量仅占给药剂量的14%。

The major elimination route of moxisylyte is via the kidneys. The complete elimination of all the metabolites by urine is of 75% when administered intravenously and 69% when administered orally. From the elimination profile, The specific ranges of the two major metabolites of moxisylyte in the urine are of 50% and 10% for desacetyl-thymoxamine and N-monodemethyl-desacetyl-thymoxamine respectively. The fecal elimination corresponded only to the 14% of the administered dose.

来源:DrugBank

吸收、分配和排泄

• 分布容积

在临床前试验中，比格犬的分布体积范围在0.83-0.98升/千克。

In preclinical trials, the volume of distribution presented for beagle dogs is in the range of 0.83-0.98 L/kg.

来源:DrugBank

吸收、分配和排泄

• 清除

在临床前试验中，比格犬的血浆清除率为7.17毫升/分钟/千克。

In preclinical trials, the plasma clearance was of 7.17 ml min/kg for beagle dogs.

来源:DrugBank

安全信息

• 海关编码：
  2922509090

反应信息

• 作为反应物：
  描述：

  莫西赛利 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以93%的产率得到2-(4-羟基-5-甲基-2-丙-2-基苯氧基)乙基-二甲基氯化铵
  参考文献：
  名称：

  Nitrosated and nitrosylated alpha-adrenergic receptor antagonists, compositions and methods of use

  摘要：

  本发明描述了新型硝化和/或硝基化α-肾上腺素受体拮抗剂，以及包含至少一种硝化和/或硝基化α-肾上腺素受体拮抗剂的新型组合物，以及可选地包含一种或多种捐赠、转移或释放一氧化氮、提高内源性内皮衍生松弛因子水平、刺激内源性一氧化氮合成或是一氧化氮合成酶底物的化合物，和/或一种或多种血管活性药物。本发明还提供了包含至少一种α-肾上腺素受体拮抗剂和一种或多种捐赠、转移或释放一氧化氮、提高内源性内皮衍生松弛因子水平、刺激内源性一氧化氮合成或是一氧化氮合成酶底物，和/或一种或多种血管活性药物的新型组合物。本发明还提供了用于治疗或预防男性和女性的性功能障碍、增强男性和女性的性反应，以及治疗或预防良性前列腺增生、高血压、充血性心力衰竭、变异性（Printzmetal）心绞痛、青光眼、神经退行性疾病、血管痉挛性疾病、认知障碍、急迫性尿失禁或过度活跃膀胱，以及逆转麻醉状态的方法。

  公开号：

  US20020143007A1
• 作为产物：
  描述：

  2-(4-羟基-5-甲基-2-丙-2-基苯氧基)乙基-二甲基氯化铵 以98%的产率得到
  参考文献：
  名称：

  MADZAKI, MITSUO;TAKEHDA, XIROMITSU;YAMAKAVA, TOMIO

  摘要：

  DOI：

文献信息

• Dibenzyl Amine Compounds and Derivatives
  申请人：Chang George

  公开号：US20070213371A1

  公开（公告）日：2007-09-13

  Dibenzyl amine compounds and derivatives, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases in some mammals, including humans.

  二苯基胺化合物及其衍生物，含有这种化合物的药物组合物以及使用这种化合物提高某些血浆脂质水平，包括高密度脂蛋白胆固醇，并降低其他一些血浆脂质水平，如低密度脂蛋白胆固醇和甘油三酯，并据此治疗由高密度脂蛋白胆固醇水平低和/或低密度脂蛋白胆固醇和甘油三酯水平高加重的疾病，如动脉粥样硬化和心血管疾病在某些哺乳动物，包括人类。
• 5-HT RECEPTOR MODULATORS
  申请人：Kapadnis Prashant Bhimrao

  公开号：US20130053372A1

  公开（公告）日：2013-02-28

  The invention relates to compounds of formula (I), useful for treating disorders mediated by the 5-hydroxytryptamine (serotonin) receptor IB (5-HT1B), e.g. vascular disorders, cancer and CNS disorders. The invention also provides methods of treating such disorders, and compounds and compositions etc. for their treatment.

  本发明涉及式(I)化合物，用于治疗由5-羟基色胺（血清素）受体IB（5-HT1B）介导的疾病，例如血管疾病、癌症和CNS疾病。本发明还提供了治疗这些疾病的方法，以及用于治疗的化合物和组合物等。
• SUBSTITUTED AMIDE COMPOUNDS
  申请人：Pfizer Inc.

  公开号：US20140315928A1

  公开（公告）日：2014-10-23

  The present invention is directed at substituted amide compounds, pharmaceutical compositions containing such compounds and the use of such compounds to reduce plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans.

  本发明涉及替代酰胺化合物，含有这种化合物的药物组合物以及利用这种化合物降低血浆脂质水平，如LDL-胆固醇和甘油三酯，并据此治疗由高水平的LDL-胆固醇和甘油三酯加重的疾病，如动脉粥样硬化和心血管疾病，在哺乳动物，包括人类中的应用。
• Novel N-acylated heterocycles
  申请人：Recordati S.A.

  公开号：US20030162777A1

  公开（公告）日：2003-08-28

  Described are compositions comprising a muscarinic receptor antagonist and an N-acylated heterocycle derivative having affinity for serotonergic receptors, and enantiomers, diastereoisomers, N-oxides, polymorphs, solvates and pharmaceutically acceptable salts thereof. The combination of a muscarinic receptor antagonist and an N-acylated heterocycle, or an enantiomer, diastereoisomer, N-oxide, polymorph, solvate or pharmaceutically acceptable salt thereof, is useful in the treatment of patients with neuromuscular dysfunction of the lower urinary tract and diseases related to 5-HT 1A receptors.

  描述了包含一种肌氨酸受体拮抗剂和一种对5-HT 1A 受体具有亲和力的N-酰化杂环衍生物的组合物，以及它们的对映体、二对映体、N-氧化物、多型体、溶剂合物和药用可接受盐。肌氨酸受体拮抗剂和N-酰化杂环，或其对映体、二对映体、N-氧化物、多型体、溶剂合物或药用可接受盐的组合，在治疗患有下尿路神经肌肉功能障碍和与5-HT 1A 受体相关疾病的患者中是有用的。
• Tyrosine kinase inhibitors
  申请人：——

  公开号：US20020137755A1

  公开（公告）日：2002-09-26

  The present invention relates to compounds which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals.

  本发明涉及抑制、调节和/或调控酪氨酸激酶信号传导的化合物，含有这些化合物的组合物，以及使用它们治疗依赖于酪氨酸激酶的疾病和病况的方法，如在哺乳动物中的血管生成、癌症、肿瘤生长、动脉粥样硬化、老年性黄斑变性、糖尿病视网膜病变、炎症性疾病等。