培格列扎 | 331744-64-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 培格列扎
• 中文别名: 草酸酯1,3-二氯-α-[2-(二丁基氨基)乙基]-6-(三氟甲基)菲-9-甲醇酸
• 英文名称: [14C]-Peliglitazar
• 英文别名: Peliglitazar；2-[(4-methoxyphenoxy)carbonyl-[(1S)-1-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]ethyl]amino]acetic acid
• CAS: 331744-64-0
• 化学式: C₃₀H₃₀N₂O₇
• 分子量: 530.577
• InChiKey: CUADMYMMZWFUCY-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  培格列扎 、 L-赖氨酸 以 乙醇 为溶剂， 反应 3.0h， 生成 peliglitazar
  参考文献：
  名称：

  PROCESS FOR PREPARING NOVEL CRYSTALLINE FORMS OF PELIGLITAZAR, NOVEL STABLE FORMS PRODUCED THEREIN AND FORMULATIONS

  摘要：

  本发明提供了一种选择性制备新型稳定晶型的工艺，即选择性和一致地制备游离酸佩利格利他酯的N-1形式、游离酸佩利格利他酯的N-2形式和游离酸佩利格利他酯的L-赖氨酸盐的P-1形式。该工艺优选采用产生具有适当流动性和所需粒径的晶体的溶剂系统。本发明还提供了新型游离酸N-1晶体、游离酸N-2晶体、游离酸L-赖氨酸盐P-1晶体的制药组合物，以及采用这些新型晶体治疗糖尿病、血脂异常和动脉粥样硬化的方法。

  公开号：

  US20070238770A1
• 作为产物：
  描述：

  methyl 2-[(4-methoxyphenoxy)carbonyl-[(1S)-1-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]ethyl]amino]acetate 以63的产率得到培格列扎
  参考文献：
  名称：

  Substituted acid derivatives useful as antidiabetic and antiobesity agents and method

  摘要：

  提供了一些具有以下结构的化合物，其中Q为C或N，A为O或S，Z为O或键，X为CH或N，R1、R2、R2a、R2b、R2c、R3、Y、x、m和n的定义如本文所述。这些化合物可用作抗糖尿病、降血脂和抗肥胖剂。

  公开号：

  US06653314B2

文献信息

• Plasma Stability-Dependent Circulation of Acyl Glucuronide Metabolites in Humans: How Circulating Metabolite Profiles of Muraglitazar and Peliglitazar Can Lead to Misleading Risk Assessment
  作者：Donglu Zhang、Nirmala Raghavan、Lifei Wang、Yongjun Xue、Mary Obermeier、Stephanie Chen、Shiwei Tao、Hao Zhang、Peter T. Cheng、Wenying Li、Ragu Ramanathan、Zheng Yang、W. Griffith Humphreys

  DOI：10.1124/dmd.110.035048

  日期：2011.1

  Muraglitazar and peliglitazar, two structural analogs differing by a methyl group, are dual peroxisome proliferator-activated receptor-α/γ activators. Both compounds were extensively metabolized in humans through acyl glucuronidation to form 1- O -β-acyl glucuronide (AG) metabolites as the major drug-related components in bile, representing at least 15 to 16% of the dose after oral administration. Peliglitazar AG was the major circulating metabolite, whereas muraglitazar AG was a very minor circulating metabolite in humans. Peliglitazar AG circulated at lower concentrations in animal species than in humans. Both compounds had a similar glucuronidation rate in UDP-glucuronic acid-fortified human liver microsomal incubations and a similar metabolism rate in human hepatocytes. Muraglitazar AG and peliglitazar AG were chemically synthesized and found to be similarly oxidized through hydroxylation and O -demethylation in NADPH-fortified human liver microsomal incubations. Peliglitazar AG had a greater stability than muraglitazar AG in incubations in buffer, rat, or human plasma (pH 7.4). Incubations of muraglitazar AG or peliglitazar AG in plasma produced more aglycon than acyl migration products compared with incubations in the buffer. These data suggested that the difference in plasma stability, not differences in intrinsic formation, direct excretion, or further oxidation of muraglitazar AG or peliglitazar AG, contributed to the observed difference in the circulation of these AG metabolites in humans. The study demonstrated the difficulty in doing risk assessment based on metabolite exposure in plasma because the more reactive muraglitazar AG would not have triggered a threshold of concern based on the recent U.S. Food and Drug Administration guidance on Metabolites in Safety Testing, whereas the more stable peliglitazar AG would have.

  Muraglitazar 和 peliglitazar 是两种结构相似的显著不同于一个甲基组的化合物，都是双重的过氧化物增殖物活化受体-α/γ 激活剂。这两种化合物在人体内经过酰基葡萄糖醛酸化被广泛代谢，形成 1-O-β-酰基葡萄糖醛酸（AG）代谢物，作为胆汁中主要的药物相关成分，口服给药后至少占剂量的 15% 到 16%。在体内，peliglitazar AG 是主要的循环代谢物，而 muraglitazar AG 在人体内则是非常微量的循环代谢物。与人类相比，peliglitazar AG 在动物种群中以较低浓度循环。这两种化合物在 UDP-葡萄糖醛酸强化的人肝微粒体培养中具有相似的葡萄糖醛酸化速率，而在人体肝细胞中的代谢速率也相似。Muraglitazar AG 和 peligrositazar AG 经过化学合成，被发现通过氢氧化和 O-去甲基化在 NADPH 强化的人肝微粒体培养中有相似的氧化反应。相比于 muraglitazar AG，peliglitazar AG 在缓冲液、鼠或人类血浆（pH 7.4）的培养中表现出更大的稳定性。与在缓冲液中的培养相比，muraglitazar AG 或 peliglitazar AG 在血浆中的培养中产生了更多的无糖部分而不是酰基迁移产物。这些数据表明，血浆稳定性之间的差异，而不是 muraglitazar AG 或 peliglitazar AG 内在形成、直接排泄或进一步氧化的差异，导致了在人体中观察到的这两种 AG 代谢物循环的差异。这项研究表明，基于血浆中代谢物暴露进行风险评估的困难，因为反应性更强的 muraglitazar AG 不会根据美国食品和药物管理局关于安全性测试中代谢物的最新指导触发关注的阈值，而更稳定的 peliglitazar AG 则会。
• COMPOUNDS AND METHODS FOR TREATING INSULIN RESISTANCE SYNDROME
  申请人：Cohen Stephen Michael

  公开号：US20140227289A1

  公开（公告）日：2014-08-14

  The present invention relates to a method of treating or preventing insulin resistance syndrome in an animal body by administering an inhibitor of protein kinase RNA-like endoplasmic reticulum kinase (PERK) gene, or a functional variant thereof, or an inhibitor of PERK protein or a functional variant thereof or a method of reducing activity of transcription factors of the FOXO family (Foxo 1, 3a, 4 and 6) by administering an inhibitor of protein kinase RNA-like endoplasmic reticulum kinase (PERK) gene, or a functional variant thereof, or an inhibitor of PERK protein or a functional variant thereof. The present invention also relates to different compounds and methods for using PERK gene or PERK protein.

  本发明涉及通过给动物体内注射蛋白激酶RNA样内质网激酶（PERK）基因的抑制剂或其功能变体，或PERK蛋白或其功能变体的抑制剂，或通过给动物体内注射蛋白激酶RNA样内质网激酶（PERK）基因的抑制剂或其功能变体，或PERK蛋白或其功能变体的抑制剂来减少FOXO家族转录因子（Foxo 1、3a、4和6）活性的方法，用于治疗或预防动物体内的胰岛素抵抗综合征。本发明还涉及不同的化合物和使用PERK基因或PERK蛋白的方法。
• PROPHYLACTIC AGENT AND/OR THERAPEUTIC AGENT FOR CATARACT, MEDICINAL COMPOSITION FOR PREVENTING AND/OR TREATING CATARACT, USE OF PPAR ACTIVATOR FOR PRODUCING SAME, AND EYEDROPS
  申请人：University of Fukui

  公开号：EP3733203A1

  公开（公告）日：2020-11-04

  Provided are agents for prevention and therapeutic treatment of cataract that act by a different mechanism from conventional agents, and use of a PPAR activator for production of such agents. An agent for prevention and/or therapeutic treatment of cataract, containing a PPAR activator as an active ingredient, is used.

  本发明提供了预防和治疗白内障的药剂，其作用机理与传统药剂不同，还提供了使用 PPAR 激活剂生产此类药剂的方法。一种用于预防和/或治疗白内障的药剂含有 PPAR 激活剂作为活性成分。
• Methods of Treating Neuropathic Pain with Agonists of PPAR-gamma
  申请人：Chiang Lillian W.

  公开号：US20100076037A1

  公开（公告）日：2010-03-25

  Embodiments of the invention relate to the treatment of neuropathic pain in mammals. Embodiments of the invention include methods for treating neuropathic pain as well as methods for preparing medicaments used in the treatment of mammalian pain. Preferably, methods of the invention comprise the use of PPARgamma agonists for the treatment of mammalian pain.
• US7241780B2
  申请人：——

  公开号：US7241780B2

  公开（公告）日：2007-07-10