(S)-tert-butyl 1-(2-chloroacetyl)pyrrolidine-2-carboxylate | 197453-33-1

• 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
• 英文名称: (S)-tert-butyl 1-(2-chloroacetyl)pyrrolidine-2-carboxylate
• 英文别名: Tert-butyl (2S)-1-(2-chloroacetyl)pyrrolidine-2-carboxylate
• CAS: 197453-33-1
• 化学式: C₁₁H₁₈ClNO₃
• 分子量: 247.722
• InChiKey: PRRTURZXKQELNR-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 1-(2-chloroacetyl)pyrrolidine-2-carboxylate 在 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 12.25h， 生成 (S)-1-[2-((3S,6R,7aR)-3-Carbamoyl-5-oxo-hexahydro-pyrrolo[2,1-b]thiazol-6-ylamino)-acetyl]-pyrrolidine-2-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Design, Synthesis, and Dopamine Receptor Modulating Activity of Diketopiperazine Peptidomimetics of l-Prolyl-l-leucylglycinamide

  摘要：

  The diketopiperazine ''C5'' conformational mimic has been incorporated into the L-prolyl-L-leucylglycinamide (PLG,1) structure and into the bicyclic lactam PLG peptidomimetic structure 3 to give compounds 5 and 6, respectively. These analogues were designed to explore the idea that the N-terminal ''C5'' conformation, which was found in the crystal structure of 2 and which was mimicked in 4 by the diketopiperazine function, was a factor in the high potency of these two agents. Through the use of the [H-3]spiroperidol/N-propylnorapomorphine (NPA) D-2 receptor competitive binding assay, both 5 and 6 were found to increase the affinity of the dopamine receptor for agonists and both were found to increase the percentage of D-2 receptors which existed in the high-affinity state. These effects were observed when Gpp(NH)p was either absent or present, and they were analogous to the effects observed previously for PLG and the PLG peptidomimetics 2 and 4. However, the potency seen with 5 and 6 was less than that seen for 2 and 4, suggesting that while the N-terminal ''C5'' conformation may play a role in the potency of the gamma-lactam peptidomimetics of PLG, it does not appear to be the primary factor. In the 6-hydroxydopamine-lesioned animal model of Parkinson's disease, 5 altered apomorphine-induced rotational behavior in a dose-dependent manner. The maximum effect occurred at a dose of 0.01 mg/kg ip and resulted in a 52.27 +/- 13.96% (p < 0.001, n = 7) increase in rotations compared to apomorphine administered alone.

  DOI：

  10.1021/jm970328b
• 作为产物：
  描述：

  N-Cbz-L-脯氨酸叔丁酯 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 25.0 ℃ 、275.79 kPa 条件下， 反应 6.0h， 生成 (S)-tert-butyl 1-(2-chloroacetyl)pyrrolidine-2-carboxylate
  参考文献：
  名称：

  Design, Synthesis, and Dopamine Receptor Modulating Activity of Diketopiperazine Peptidomimetics of l-Prolyl-l-leucylglycinamide

  摘要：

  The diketopiperazine ''C5'' conformational mimic has been incorporated into the L-prolyl-L-leucylglycinamide (PLG,1) structure and into the bicyclic lactam PLG peptidomimetic structure 3 to give compounds 5 and 6, respectively. These analogues were designed to explore the idea that the N-terminal ''C5'' conformation, which was found in the crystal structure of 2 and which was mimicked in 4 by the diketopiperazine function, was a factor in the high potency of these two agents. Through the use of the [H-3]spiroperidol/N-propylnorapomorphine (NPA) D-2 receptor competitive binding assay, both 5 and 6 were found to increase the affinity of the dopamine receptor for agonists and both were found to increase the percentage of D-2 receptors which existed in the high-affinity state. These effects were observed when Gpp(NH)p was either absent or present, and they were analogous to the effects observed previously for PLG and the PLG peptidomimetics 2 and 4. However, the potency seen with 5 and 6 was less than that seen for 2 and 4, suggesting that while the N-terminal ''C5'' conformation may play a role in the potency of the gamma-lactam peptidomimetics of PLG, it does not appear to be the primary factor. In the 6-hydroxydopamine-lesioned animal model of Parkinson's disease, 5 altered apomorphine-induced rotational behavior in a dose-dependent manner. The maximum effect occurred at a dose of 0.01 mg/kg ip and resulted in a 52.27 +/- 13.96% (p < 0.001, n = 7) increase in rotations compared to apomorphine administered alone.

  DOI：

  10.1021/jm970328b

文献信息

• [EN] SUBSTITUTED PIPERIDIN-4-AMINO-TYPE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS DE TYPE PIPÉRIDINE-4-AMINO SUBSTITUÉE ET LEURS UTILISATIONS
  申请人：PURDUE PHARMA LP

  公开号：WO2014102590A1

  公开（公告）日：2014-07-03

  The disclosure relates to Substituted Piperidin-4-amino-Type Compounds of Formula (I) and pharmaceutically acceptable salts and solvates thereof wherein R1, R2, R3, Q1, Q2, E1, E2, A, B, D, W, Z, a, b, n, and x are as defined herein, compositions comprising an effective amount of a Substituted Piperidin-4-amino-Type Compound, and methods to treat or prevent a condition, such as pain, comprising administering to an animal in need thereof an effective amount of a Substituted Piperidin-4-amino-Type Compound.

  本发明涉及式(I)的取代哌啶-4-氨基型化合物及其药物可接受的盐和溶剂化物，其中R1，R2，R3，Q1，Q2，E1，E2，A，B，D，W，Z，a，b，n和x按本文定义，包含有效量的取代哌啶-4-氨基型化合物的组合物，以及治疗或预防诸如疼痛等症状的方法，包括向需要的动物施用有效量的取代哌啶-4-氨基型化合物。
• 1-[[(3-Hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(<i>S</i>)-pyrrolidine:  A Potent, Selective, and Orally Bioavailable Dipeptidyl Peptidase IV Inhibitor with Antihyperglycemic Properties
  作者：Edwin B. Villhauer、John A. Brinkman、Goli B. Naderi、Bryan F. Burkey、Beth E. Dunning、Kapa Prasad、Bonnie L. Mangold、Mary E. Russell、Thomas E. Hughes

  DOI：10.1021/jm030091l

  日期：2003.6.1

  Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. The synthesis and structure-activity relationship of a new DPP-IV inhibitor class, N-substituted-glycyl-2-cyanopyrrolidines, are described as well as the path that led from clinical development compound 1-[2-[5-cyanopyridin-2-yl)amino]ethylamino]acetyl-2-cyano-(S)-pyrrolidine (NVP-DPP728

  抑制二肽基肽酶IV（DPP-IV）可能成为2型糖尿病的有价值的治疗方法。描述了新型DPP-IV抑制剂类N-取代的甘氨酰-2-氰基吡咯烷类化合物的合成与构效关系，以及从临床开发化合物1- [2- [5-氰基吡啶-2]开始的途径-基）氨基]乙基氨基]乙酰基-2-氰基-（S）-吡咯烷（NVP-DPP728，8c）进行后续研究，[1-[[（（3-羟基-1-金刚烷基）氨基]乙酰基] -2 -氰基-（S）-吡咯烷（NVP-LAF237，12j）。讨论了肥胖Zucker fa / fa大鼠中12j的药理学特征以及正常食蟹猴中8c和12j的药代动力学特征。结果表明12j是有效，稳定，
• PRODRUGS OF METHYL HYDROGEN FUMARATE, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USE
  申请人：Gangakhedkar Archana

  公开号：US20100048651A1

  公开（公告）日：2010-02-25

  Prodrugs of methyl hydrogen fumarate, pharmaceutical compositions comprising prodrugs of methyl hydrogen fumarate, and methods of using prodrugs of methyl hydrogen fumarate and pharmaceutical compositions thereof for treating diseases such as psoriasis, asthma, multiple sclerosis, inflammatory bowel disease, and arthritis are disclosed.

  本文披露了甲基氢富马酸的前药、包含甲基氢富马酸前药的药物组合物，以及使用甲基氢富马酸前药和药物组合物治疗诸如牛皮癣、哮喘、多发性硬化症、炎症性肠病和关节炎等疾病的方法。
• METHODS OF USING PRODRUGS OF METHYL HYDROGEN FUMARATE AND PHARMACEUTICAL COMPOSITIONS THEREOF
  申请人：Gangakhedkar Archana

  公开号：US20120095003A1

  公开（公告）日：2012-04-19

  Prodrugs of methyl hydrogen fumarate, pharmaceutical compositions comprising prodrugs of methyl hydrogen fumarate, and methods of using prodrugs of methyl hydrogen fumarate and pharmaceutical compositions thereof for treating diseases such as psoriasis, asthma, multiple sclerosis, inflammatory bowel disease, and arthritis are disclosed.

  本发明涉及甲基氢富马酸的前药、包含甲基氢富马酸前药的制药组合物以及使用甲基氢富马酸前药和制药组合物治疗诸如银屑病、哮喘、多发性硬化症、炎症性肠病和关节炎等疾病的方法。
• Prodrugs of methyl hydrogen fumarate, pharmaceutical compositions thereof, and methods of use
  申请人：XenoPort, Inc.

  公开号：US08148414B2

  公开（公告）日：2012-04-03

  Prodrugs of methyl hydrogen fumarate, pharmaceutical compositions comprising prodrugs of methyl hydrogen fumarate, and methods of using prodrugs of methyl hydrogen fumarate and pharmaceutical compositions thereof for treating diseases such as psoriasis, asthma, multiple sclerosis, inflammatory bowel disease, and arthritis are disclosed.

  本发明涉及甲基氢富马酸的前药、包含甲基氢富马酸前药的制剂，以及使用甲基氢富马酸前药和制剂治疗诸如牛皮癣、哮喘、多发性硬化症、炎症性肠病和关节炎等疾病的方法。