马西瑞林 | 381231-18-1

• 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: 马西瑞林
• 英文名称: Macimorelin
• 英文别名: 2-amino-N-[(2R)-1-[[(1R)-1-formamido-2-(1H-indol-3-yl)ethyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-methylpropanamide
• CAS: 381231-18-1
• 化学式: C₂₆H₃₀N₆O₃
• 分子量: 474.6
• InChiKey: UJVDJAPJQWZRFR-DHIUTWEWSA-N

物化性质

• 沸点：
  948.6±65.0 °C(Predicted)
• 密度：
  1.309±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  145
• 氢给体数：
  6
• 氢受体数：
  4

ADMET

代谢

根据一项体外人肝脏微粒体研究，Macimorelin主要通过CYP3A4介导的代谢过程。

Macimorelin predominantly undergoes CYP3A4-mediated metabolism according to an *in vitro* human liver microsomes study.

来源:DrugBank

吸收、分配和排泄

• 吸收

Macimorelin是一种新型、合成的生长激素释放肽（ghrelin）激动剂，能够从胃肠道被很好地吸收。在禁食至少8小时的功能性生长激素缺乏症（AGHD）患者口服0.5mg/kg的Macimorelin后，最大血浆浓度（Cmax）在0.5到1.5小时之间观察到。更高剂量的药物显示出与剂量成正比的血浆浓度增加。液体餐减少了Macimorelin的Cmax和AUC，分别降低了55%和49%。

Macimorelin is a novel, synthetic ghrelin agonist, which is readily absorbed from the gastrointestinal tract. The maximum plasma concentration (Cmax) was observed between 0.5 and 1.5 hours following oral administration of 0.5mg/kg macimorelin to patients with AGHD under fasting for at least 8 hours. Higher doses of drug demonstrate a dose-proportional increase in plasma concentrations. A liquid meal decreased the macimorelin Cmax and AUC by 55% and 49%, respectively.

来源:DrugBank

吸收、分配和排泄

• 分布容积

在单次口服剂量为0.5毫克/千克的macimorelin后，中央室的平均分布体积为5,733.4 ± 565.7升。

Following a single oral dose of 0.5 mg/kg macimorelin, the mean volume of distribution of the central compartment is 5,733.4 ± 565.7L.

来源:DrugBank

吸收、分配和排泄

• 清除

在单次口服剂量为0.5毫克/千克的macimorelin后，吸收部分的平均清除率（Cl/F）为37,411.0 ± 4,554.6毫升/分钟。

Following a single oral dose of 0.5 mg/kg macimorelin, the mean clearance over the fraction absorbed (Cl/F) was 37,411.0 ± 4,554.6 mL/min.

来源:DrugBank

文献信息

• Organic compounds
  申请人：Beattie David

  公开号：US20100035898A1

  公开（公告）日：2010-02-11

  There are described cyclohexyl amide derivatives useful as corticotropin releasing factor (CRF 1 ) receptor antagonists.

  描述了环己基酰胺衍生物，可用作促肾上腺皮质激素释放因子（CRF1）受体拮抗剂。
• PYRAZOLO[5,1B]OXAZOLE DERIVATIVES AS CRF-1 RECEPTOR ANTAGONISTS
  申请人：Devereux Nicholas James

  公开号：US20110190360A1

  公开（公告）日：2011-08-04

  There are described 4-difluoromethoxyphenyl pyrazolo[5.1-b]oxazole derivatives of Formula I: which are useful as corticotropin releasing factor (CRF) receptor antagonists and as pharmaceuticals.

  描述了Formula I的4-二氟甲氧基苯基吡唑[5.1-b]噁唑衍生物，这些衍生物可用作促肾上腺皮质激素释放因子（CRF）受体拮抗剂和药物。
• Quinazolinone Derivatives Useful as Vanilloid Antagonists
  申请人：Chen Weichun

  公开号：US20100197705A1

  公开（公告）日：2010-08-05

  There is described a new polymorphic form of 4-(7-Hydroxy-2-isopropyl-4-oxo-4H-quinazolin-3-yl)-benzonitrile having structural formula I(B) and to a method of preparing it. There is further a process or method for the manufacture of a pharmaceutically active quinazolinone compounds of the formula I wherein the symbols have the meanings given in the description, said process comprising reacting a compound of the formula II, wherein R 4 * is R 1 *—C(═O)— wherein R 1 * is independently selected from the group of meanings of R 1 as defined for a compound of the formula I so that R 1 * and R 1 are identical to or different from each other, or R 4 * is especially H, and R 1 and R 3 , R 5 and R 6 are as defined for a compound of the formula I, or a salt thereof, under simultaneous or sequential condensation and cyclisation conditions with an aniline compound of the formula III, wherein R 2 and m are as defined for a compound of the formula I. Further reactions and related embodiments are also claimed and disclosed.

  本文描述了一种4-(7-羟基-2-异丙基-4-氧代-4H-喹唑啉-3-基)-苯甲腈的新多晶型式I(B)，以及其制备方法。此外，本文还提供了一种制备具有式I中所给符号所表示含义的药物活性喹唑啉酮化合物的过程或方法，该过程包括将式II的化合物与式III的苯胺化合物在同时或顺序缩合和环化条件下反应，其中R4*为R1*—C(═O)—，其中R1*独立地选自于式I化合物所定义的R1的含义组，使得R1*和R1相同或不同，或R4*特别为H，而R1和R3、R5和R6如式I中所定义，或其盐。本文还声明和揭示了进一步的反应和相关实施方式。
• CYCLOHEXYL AMIDE DERIVATIVES AS CRF RECEPTOR ANTAGONISTS
  申请人：Atkinson Benjamin

  公开号：US20110201629A1

  公开（公告）日：2011-08-18

  There are described cyclohexyl amide derivatives of Formula I, which are useful as corticotropin releasing factor (CRF) receptor antagonists and as pharmaceuticals.

  描述了一种公式I的环己基酰胺衍生物，其作为促肾上腺皮质激素释放因子（CRF）受体拮抗剂和药物是有用的。
• Pyrazolo[5,1b]oxazole Derivatives as CRF-1 Receptor Antagonists
  申请人：Devereux Nicholas James

  公开号：US20120295942A1

  公开（公告）日：2012-11-22

  There are described 4-difluoromethoxyphenyl pyrazolo[5.1-b]oxazole derivatives useful as corticotropin releasing factor (CRF 1 ) receptor antagonists.

  这是一种描述了4-二氟甲氧基苯基吡唑并[5.1-b]噁唑衍生物，可用作促肾上腺皮质激素释放因子（CRF1）受体拮抗剂。