1-(1,2-二氧代-3,3-二甲基戊基)-L脯氨酸-(3-吡啶基)-丙酯 | 186452-09-5

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 脯氨酸类衍生物
• 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: 1-(1,2-二氧代-3,3-二甲基戊基)-L脯氨酸-(3-吡啶基)-丙酯
• 中文别名: (S)-3-(吡啶-3-基)丙基1-(3,3-二甲基-2-氧代戊酰基)吡咯烷-2-羧酸；1-(1,2-二氧代-3,3-二甲基戊基)-L-脯氨酸(3-吡啶基)丙酯；1-(1,2-二氧代-3,3-二甲基戊基)-L-脯氨酸 (3-吡啶基)丙酯
• 英文名称: 3-(3-pyridyl)-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidinecarboxylate
• 英文别名: GPI-1046；(S)-3-(Pyridin-3-yl)propyl 1-(3,3-dimethyl-2-oxopentanoyl)pyrrolidine-2-carboxylate；3-pyridin-3-ylpropyl (2S)-1-(3,3-dimethyl-2-oxopentanoyl)pyrrolidine-2-carboxylate
• CAS: 186452-09-5
• 化学式: C₂₀H₂₈N₂O₄
• 分子量: 360.453
• InChiKey: OQAHHWOPVDDWHD-INIZCTEOSA-N

物化性质

• 沸点：
  501.5±60.0 °C(Predicted)
• 密度：
  1.143±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  76.6
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090
• 储存条件：
  -20°C，密封保存，并保持干燥。

制备方法与用途

生物活性

GPI-1046 是一种不含抗生素作用的免疫亲和素配体，通过上调 PFC 和 NAc 核心中的谷氨酸转运蛋白 1 (GLT1) 来减少乙醇摄入。GPI-1046 类似于 FK506，在神经退行性疾病模型中显示出神经保护作用。GPI-1046 易穿过血脑屏障并促进中枢神经系统中多巴胺 (DA) 细胞的再生，这与啮齿动物模型中的功能恢复相关。此外，GPI-1046 还可改善 HIV 相关的周围神经损伤。

靶点

GLT1

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	2-(E)-ethyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidine-carboxylate	1233885-04-5	C14H23NO4	269.341
  (2S)-1-(1,2-二氧代-3,3-二甲基戊基)-2-吡咯烷甲酸	(2S)-1-(1,2-dioxo-3 3-dimethylpentyl)-2-pyrrolidinecarboxylic acid	186268-78-0	C12H19NO4	241.287

反应信息

• 作为产物：
  描述：

  2-(E)-ethyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidine-carboxylate 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 lithium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 1-(1,2-二氧代-3,3-二甲基戊基)-L脯氨酸-(3-吡啶基)-丙酯
  参考文献：
  名称：

  Evaluation of Synthetic FK506 Analogues as Ligands for the FK506-Binding Proteins 51 and 52

  摘要：

  The FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal transduction of steroid hormone receptors. Both proteins have been implicated in prostate cancer. Furthermore, single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products that bind to these proteins indiscriminately but with nanomolar affinity. We here report the cocrystal structure of FKBP51 with a simplified alpha-ketoamide analogue derived from FK506 and the first structure-activity relationship analysis for FKBP51 and FKBP52 based on this compound. In particular, the tert-pentyl group of this ligand was systematically replaced by a cyclohexyl ring system, which more closely resembles the pyranose ring in the high-affinity ligands rapamycin and FK506. The interaction with FKBPs was found to be surprisingly tolerant to the stereochemistry of the attached cyclohexyl substituents. The molecular basis for this tolerance was elucidated by X-ray cocrystallography.

  DOI：

  10.1021/jm201746x

文献信息

• Small molecule inhibitors of rotamase enzyme
  申请人：Guilford Pharmaceuticals Inc.

  公开号：US05614547A1

  公开（公告）日：1997-03-25

  This invention relates to neurotrophic compounds having an affinity for FKBP-type immunophilins, their preparation and use as inhibitors of the enzyme activity associated with immunophilin proteins, and particularly inhibitors of peptidyl-prolyl isomerase or rotamase enzyme activity.

  本发明涉及具有FKBP型免疫蛋白亲和力的神经营养因子化合物，它们的制备以及用作免疫蛋白蛋白酶酶活性抑制剂的用途，特别是用作肽基-脯氨酸异构酶或转轮酶酶活性的抑制剂。
• Compounds for treating inflammatory disorders, demyelinating disdorders and cancers
  申请人：Ajami M. Alfred

  公开号：US20080108641A1

  公开（公告）日：2008-05-08

  Compounds of formula (I) and a method of treating a patient suffering from an inflammatory and/or demyelinating disorders, comprising administering to said patient a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. Definitions for the variables are provided therein.

  公式（I）的化合物及治疗患有炎症和/或脱髓鞘性疾病的患者的方法，包括向该患者施用公式（I）的化合物或其药学上可接受的盐的治疗有效量。其中提供了变量的定义。
• Indazole Compounds for Treating Inflammatory Disorders, Demyelinating Disorders and Cancers
  申请人：Ajami Alfred M.

  公开号：US20100292231A1

  公开（公告）日：2010-11-18

  Compounds of formula (I) or formula (Ia) and a method of treating a patient suffering from certain inflammatory disorders, demyelinating disorders, FLT3-mediated disorders, CSF-1R-mediated disorders, cancers and leukemias, comprising administering to said patient a therapeutically effective amount of a compound of formula (I) or formula (Ia) or a pharmaceutically acceptable salt thereof. Definitions for the variables are provided herein.

  本发明涉及具有公式（I）或公式（Ia）的化合物以及治疗患有某些炎症性疾病、脱髓鞘性疾病、FLT3介导的疾病、CSF-1R介导的疾病、癌症和白血病的患者的方法，包括向该患者施用公式（I）或公式（Ia）的化合物或其药学上可接受的盐的治疗有效量。变量的定义在此提供。
• BRIDGED HETEROCYCLIC DERIVATIVES
  申请人：GPI NIL Holdings, Inc.

  公开号：EP1127049A1

  公开（公告）日：2001-08-29
• NEUROPHILIN LIGANDS FOR TREATING OCULAR CONDITIONS
  申请人：Alcon, Inc

  公开号：EP1227859A2

  公开（公告）日：2002-08-07