AMMC | 327594-35-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: AMMC
• 英文别名: 3-[2-(N,N-diethyl-N-methylamino)ethyl]-7-methoxy-4-methylcoumarin；3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin；US9173935, Ammc；diethyl-[2-(7-methoxy-4-methyl-2-oxochromen-3-yl)ethyl]-methylazanium
• CAS: 327594-35-4
• 化学式: C₁₈H₂₆NO₃
• 分子量: 304.409
• InChiKey: IWAUXKQGXMTXLR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

Schembl237672 已知的人类代谢物包括 AMHC（3-[2-(N,N-二乙基-N-甲基铵)乙基]-7-羟基-4-甲基香豆素）。

Schembl237672 has known human metabolites that include AMHC (3-[2-(N,N-diethyl-Nmethylammonium)ethyl]-7-hydroxy-4-methylcoumarin).

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  AMMC 在 cytochrome P₄₅₀ 2D₆ 作用下， 生成 3-[2-(N,N-diethylamino)ethyl]-7-hydroxy-4-methylcoumarin
  参考文献：
  名称：

  Pharmacokinetic evaluation of the anticancer prodrug simmitecan in different experimental animals

  摘要：

  目的 研究具有强效抗肿瘤活性的水溶性基米替康 (L-2-Z) 酯前药西米替康 (L-P) 在不同实验动物中的药代动力学和分布，并评估其药物相互作用潜力。 SD大鼠单次静脉推注剂量的L-P（3.75、7.5和15 mg/kg）。通过 LC/MS 定量测量和代谢物分析，研究了 L-P 及其活性代谢物 L-2-Z 的药代动力学、组织分布、排泄和代谢。使用超滤方法检查 L-P 和 L-2-Z 与大鼠血浆蛋白的结合。还检查了比格犬对 L-P 的全身暴露以及人肝癌 SMMC-7721 细胞裸鼠异种移植模型肿瘤中的药物分布。研究了不同物种的体外肝微粒体羧酸酯酶对 L-P 的代谢。使用商业筛选试剂盒检查 L-P 和 L-2-Z 对细胞色素 P450 酶的影响。 L-P 到 L-2-Z 的体内生物转化表现出显着的物种差异，大鼠中的平均消除半衰期 t1/2 约为 1.4 小时，狗中为 1.9 小时。 L-P和L-2-Z的全身暴露水平以剂量依赖性方式增加。在大鼠中，大约 66% 的 L-P 和 79% 的 L-2-Z 与血浆蛋白结合。在患有人类肝癌的大鼠和裸鼠中，大多数器官组织的L-P浓度显着高于相应的血浆水平。在肿瘤组织中，L-P水平与血浆相当，而L-2-Z水平低于L-P水平。在大鼠中，L-P主要通过胆汁排泄消除，但代谢在完整L-P的消除中起着重要作用。最后，L-P和L-2-Z在体外对CYP3A4的活性有中等程度的抑制作用。 L-P和L-2-Z的消除半衰期相对较短，L-P主要通过胆汁排泄消除。 L-P 转化为 L-2-Z 的物种差异以及由于 CYP3A4 抑制而导致的潜在药物间相互作用应在进一步研究中考虑。

  DOI：

  10.1038/aps.2013.74

文献信息

• [EN] URACIL-TYPE GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS AND METHODS RELATED THERETO<br/>[FR] ANTAGONISTES DE TYPE URACIL GONADOLIBÉRINE ET LES MÉTHODES AFFÉRENTES
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2005113516A1

  公开（公告）日：2005-12-01

  Compounds having utility as GnRH receptor antagonists and for treatment of a variety of sex-hormone related conditions in both men and women. Such compounds have the following structure (I): (I) wherein R1a, R1b, R1c, R2a, R2b, R3, R4, R5, R6, R7, n and X are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of structure (I) in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

  具有作为GnRH受体拮抗剂的效用，并用于治疗男性和女性的各种与性激素相关疾病的化合物。这些化合物具有以下结构（I）：（I）其中R1a、R1b、R1c、R2a、R2b、R3、R4、R5、R6、R7、n和X如本文所定义，包括立体异构体、前药和其药用可接受盐。还公开了含有结构（I）化合物的组合物，与药用可接受载体结合，以及与使用该组合物拮抗需要该物质的受试者中的促性腺激素释放激素相关的方法。
• CALCIUM-SENSING RECEPTOR-ACTIVE COMPOUNDS
  申请人：Fenscholdt Jef

  公开号：US20120101039A1

  公开（公告）日：2012-04-26

  A compound of general formula I their use as calcium receptor-active compounds for the prophylaxis, treatment or amelioration of physiological disorders or diseases associated with disturbances of CaSR activity, such as hyperparathyroidism, pharmaceutical compositions comprising said compounds, methods of treating diseases with said compounds, and the use of said compounds in the manufacture of medicaments.

  一种通用化学式I的化合物，其用作钙受体活性化合物，用于预防、治疗或改善与CaSR活性紊乱相关的生理紊乱或疾病，如甲状旁腺功能亢进症，包括所述化合物的药物组合物，使用所述化合物治疗疾病的方法，以及所述化合物用于制造药物。
• Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis
  申请人：——

  公开号：US20030236227A1

  公开（公告）日：2003-12-25

  The subject invention provides pharmaceutical compounds useful in the treatment of Type II diabetes. These compounds are advantageous because they are readily metabolized by the metabolic drug detoxification systems. Particularly, thiazolidinedione analogs that have been designed to include esters within the structure of the compounds are provided. This invention is also drawn to methods of treating disorders, such as diabetes, comprising the administration of therapeutically effective compositions comprising compounds that have been designed to be metabolized by serum or intracellular hydrolases and esterases. Pharmaceutical compositions of the ester-containing thiazolidinedione analogs are also taught.

  该发明提供了在治疗2型糖尿病中有用的药物化合物。这些化合物具有优势，因为它们可以被代谢药物解毒系统迅速代谢。特别地，设计了包含酯基的噻唑烷二酮类似物的化合物。该发明还涉及治疗疾病的方法，如糖尿病，包括给予经设计为能够被血清或细胞内酯酶代谢的化合物的治疗有效组合物。还教授了含酯基的噻唑烷二酮类似物的药物组合物。
• PYRIDINONE COMPOUNDS
  申请人：Borzilleri Robert M.

  公开号：US20080114033A1

  公开（公告）日：2008-05-15

  The invention is directed to pyridinone compounds useful for modulating Met kinase, having the following structure: and is further directed to pharmaceutical compositions comprising the compound; and methods for treating proliferative diseases, such as cancer by the administration of this compound.

  这项发明涉及对吡啶酮化合物的调节，该化合物对调节Met激酶具有以下结构： 并且还涉及包含该化合物的药物组合物；以及通过给予该化合物治疗增殖性疾病，如癌症的方法。
• [EN] PYRIMIDINE-2, 4-DIONE DERIVATIVES AS GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE PYRIMIDINE-2, 4-DIONE UTILISES COMME ANTAGONISTES DU RECEPTEUR D'HORMONE LIBERANT DE LA GONADOTROPHINE
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2005007165A1

  公开（公告）日：2005-01-27

  GnRH receptor antagonists are disclosed that have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1a, R1b, R1c, R2a, R2b, R3, R4, R5, R6 and X are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

  GnRH受体拮抗剂被披露，对男性和女性的各种与性激素相关的疾病具有治疗作用。本发明的化合物具有以下结构：其中R1a、R1b、R1c、R2a、R2b、R3、R4、R5、R6和X的定义如本文所述，包括立体异构体、前药和其药用可接受盐。还披露了含有本发明化合物的组合物与药用可接受载体的组合物，以及与在需要时对抗性腺激素释放激素的使用方法。