(S)-1-tert-butyl 2-methyl 4-(cyanomethylene)pyrrolidine-1,2-dicarboxylate | 364077-86-1

• 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)-1-tert-butyl 2-methyl 4-(cyanomethylene)pyrrolidine-1,2-dicarboxylate
• 英文别名: N-tert-butyloxycarbonyl-4-(cyanomethylen)-L-proline methyl ester；1-O-tert-butyl 2-O-methyl (2S)-4-(cyanomethylidene)pyrrolidine-1,2-dicarboxylate
• CAS: 364077-86-1
• 化学式: C₁₃H₁₈N₂O₄
• 分子量: 266.297
• InChiKey: XQKKHGKWYQBEPH-JTQLQIEISA-N

物化性质

• 沸点：
  383.7±42.0 °C(Predicted)
• 密度：
  1.237±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  79.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-1-tert-butyl 2-methyl 4-(cyanomethylene)pyrrolidine-1,2-dicarboxylate 在 platinum(IV) oxide 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 氯仿 为溶剂， 反应 21.0h， 生成 (4S)-(2-N-allyloxycarbonylaminoethyl)-L-proline methyl ester hydrotrifluoroacetate
  参考文献：
  名称：

  酰基蛋白硫酯酶1（APT1）抑制剂的合成和评估。

  摘要：

  脂质修饰的蛋白质在重要的生物学过程中起着决定性作用，例如信号转导，细胞骨架的组织和囊泡转运。这些蛋白质的脂化对于正确的生物学功能是必不可少的。在脂质修饰中，烯丙基化和肉豆蔻酰基化是众所周知的。但是，棕榈酰化的机制仍在研究中。最近，纯化了一种可能在H-Ras和G蛋白α亚基的棕榈酰化循环中起调节作用的酰基蛋白硫酯酶1（APT1）酶。受这项工作的启发，设计，合成了多种APT1抑制剂，并对其进行了生物学评估，从而产生了高活性的化合物。

  DOI：

  10.1002/chem.200501128
• 作为产物：
  描述：

  Boc-L-羟脯氨酸 在 sodium hydride 、 caesium carbonate 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.5h， 生成 (S)-1-tert-butyl 2-methyl 4-(cyanomethylene)pyrrolidine-1,2-dicarboxylate
  参考文献：
  名称：

  酰基蛋白硫酯酶1（APT1）抑制剂的合成和评估。

  摘要：

  脂质修饰的蛋白质在重要的生物学过程中起着决定性作用，例如信号转导，细胞骨架的组织和囊泡转运。这些蛋白质的脂化对于正确的生物学功能是必不可少的。在脂质修饰中，烯丙基化和肉豆蔻酰基化是众所周知的。但是，棕榈酰化的机制仍在研究中。最近，纯化了一种可能在H-Ras和G蛋白α亚基的棕榈酰化循环中起调节作用的酰基蛋白硫酯酶1（APT1）酶。受这项工作的启发，设计，合成了多种APT1抑制剂，并对其进行了生物学评估，从而产生了高活性的化合物。

  DOI：

  10.1002/chem.200501128

文献信息

• Pharmaceutically active pyrrolidine derivatives as bax inhibitors
  申请人：——

  公开号：US20030171309A1

  公开（公告）日：2003-09-11

  The present invention is related to new substituted pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of neurodegenerative disorders, diseases associated with polygultamine tracts, epilepsy, ischemia, infertility, cardiovascular disorders renal hypoxia, hepatitis and AIDS. Said pyrrolidine derivatives display a modulatory and most notably a down-regulating-up to an inhibitory-activity with respect to the cellular death agonist Bax and/or the activation pathways leading to Bax and allows therefore to block the release of cytochrome (c). The present invention is furthermore related to novel pharmaceutically activity substituted pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of O, S, CR<6>R<7>, NOR<6>, NNR<6>R<7>; A is selected from the group consisting of —(C═O)—, —(C═O)—O—, —C(═NH)—, —(C═O)—NH—, —(C═S)—NH, —SO2-, —SO2NH—; —CH2-; B is either a group —(C═O)—NR<8>R<9> or represents a heterocyclic residue having the formula (II) wherein Q is NR<10>, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring.

  本发明涉及公式（I）的新取代吡咯烷衍生物。这些化合物通常用作药物活性化合物。具体来说，公式（I）的吡咯烷衍生物在神经退行性疾病、与多谷氨酸肽段相关的疾病、癫痫、缺血、不孕症、心血管疾病、肾脏缺氧、肝炎和艾滋病的治疗和/或预防中有用。所述吡咯烷衍生物显示出调节性，特别是对细胞死亡促进剂Bax和/或导致Bax激活途径的下调-直至抑制活性，并因此允许阻止细胞色素（c）的释放。本发明还涉及新的具有药物活性的取代吡咯烷衍生物以及它们的制备方法，其中X选择自O、S、CR <6> R <7>、NOR <6>、NNR <6> R <7>的群；A选择自-（C═O）-、-（C═O）-O-、-C（═NH）-、-（C═O）-NH-、-（C═S）-NH、-SO2-、-SO2NH-；-CH2-；B是一个组-（C═O）-NR <8> R <9>或代表具有公式（II）的杂环残基，其中Q是NR <10>、O或S；n是选择的整数0、1或2；Y、Z和E与它们连接的2个碳一起形成一个5-6成员芳香族或杂芳族环。
• Pyrrolidine ester derivatives with oxytocin modulating activity
  申请人：——

  公开号：US20040147511A1

  公开（公告）日：2004-07-29

  The present invention is related to the use of pyrrolidine esters of formula (I) for the treatment and/or prevention of premature labor, premature birth and dysmenorrhea. In particular, the present invention is related to the use of pyrrolidine esters of formula (I) to modulate, notably to antagonise the oxytocin receptor. The present invention is furthermore related to novel pyrrolidine esters. X is selected from the group consisting of CR 6 R 7 , NOR 6 , NNR 6 R 7 ;R is selected from the group comprising or consisting of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, saturated or unsaturated 3-8-membered cycloalkyl which may contain 1 to 3 heteroatoms selected of N, O, S, aryl, heteroaryl, C 1 -C 6 -alkyl aryl, C 1 -C 6 -alkyl heteroaryl. R 1 is selected from the group comprising or consisting of C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl, heteroaryl, 3-8-membered cycloalkyl, acyl, C 1 -C 6 -alkyl aryl, C 1 -C 6 -alkyl heteroaryl, said cycloalkyl or aryl or heteroaryl groups may be fused with 1-2 further cycloalkyl or aryl or heteroaryl group. 1

  本发明涉及使用式（I）的吡咯烷酯治疗和/或预防早产、早产和痛经。特别是，本发明涉及使用式（I）的吡咯烷酯来调节，尤其是拮抗催产素受体。本发明还涉及新型吡咯烷酯。其中，X选自CR6R7、NOR6、NNR6R7组成的群；R选自C1-C6烷基、C2-C6烯基、C2-C6炔基、饱和或不饱和的含1到3个N、O、S杂原子的3-8环脂肪环烷基、芳基、杂环芳基、C1-C6烷基芳基、C1-C6烷基杂环芳基组成的群；R1选自C1-C6烷基、C2-C6烯基、C2-C6炔基、芳基、杂环芳基、3-8环脂肪环烷基、酰基、C1-C6烷基芳基、C1-C6烷基杂环芳基，所述环烷基或芳基或杂环芳基基团可以与1-2个进一步的环烷基或芳基或杂环芳基基团融合。
• PHARMACEUTICALLY ACTIVE PYRROLIDINE ESTER DERIVATIVES
  申请人：Schwarz Matthias

  公开号：US20070129381A1

  公开（公告）日：2007-06-07

  The present invention is related to the use of pyrrolidine esters of formula (I) for the treatment and/or prevention of premature labor, premature birth and dysmenorrhea. In particular, the present invention is related to the use of pyrrolidine esters of formula (I) to modulate, notably to antagonise the oxytocin receptor. The present invention is furthermore related to novel pyrrolidine esters. X is selected from the group consisting of CR 6 R 7 , NOR 6 , NNR 6 R 7 ; R is selected from the group comprising or consisting of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, saturated or unsaturated 3-8-membered cycloalkyl which may contain 1 to 3 heteroatoms selected of N, O, S, aryl, heteroaryl, C 1 -C 6 -alkyl aryl, C 1 -C 6 -alkyl heteroaryl. R 1 is selected from the group comprising or consisting of C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl, heteroaryl, 3-8-membered cycloalkyl, acyl, C 1 -C 6 -alkyl aryl, C 1 -C 6 -alkyl heteroaryl, said cycloalkyl or aryl or heteroaryl groups may be fused with 1-2 further cycloalkyl or aryl or heteroaryl group.

  本发明涉及使用式（I）的吡咯烷酯治疗和/或预防早产、早产和痛经。特别地，本发明涉及使用式（I）的吡咯烷酯来调节，特别是拮抗催产素受体。本发明还涉及新型吡咯烷酯。其中，X选自CR6R7、NOR6、NNR6R7组成的群；R选自C1-C6烷基、C2-C6烯基、C2-C6炔基、饱和或不饱和的3-8环成员的环烷基，可含1-3个选自N、O、S、芳基、杂芳基、C1-C6烷基芳基、C1-C6烷基杂芳基的杂原子；R1选自C1-C6烷基、C2-C6烯基、C2-C6炔基、芳基、杂芳基、3-8环成员的环烷基、酰基、C1-C6烷基芳基、C1-C6烷基杂芳基，所述环烷基或芳基或杂芳基基团可以与1-2个进一步的环烷基或芳基或杂芳基基团融合。
• Pharmaceutically active pyrrolidine derivatives
  申请人：Applied Research Systems Ars Holding N.V.

  公开号：US07211601B2

  公开（公告）日：2007-05-01

  The present invention is related to pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of premature labor, premature birth and dysmenorrhea. In particular, the present invention is related to pyrrolidine derivatives displaying a substantial modulatory, notably an antagonist activity of the oxytocin receptor. More preferably, said compounds are useful in the treatment and/or prevention of disease states mediated by oxytocin, including premature labor, premature birth and dysmenorrhea. The present invention is furthermore related to novel pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of CR6R7, NOR6, NNR6R7; A is selected from the group consisting of —(C═O)—, —(C═O)—O—, —C(═NH)—, —(C═O)—NH—, —(C═S)—NH, —SO22-, —SO2NH—, —CH2-, B is either a group —(C═O)—NR8R9 or represents a heterocyclic residue having the formula (a) wherein Q is NR10, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5–6 membered aryl or heteroaryl ring.

  本发明涉及式(I)的吡咯烷衍生物。所述化合物优选用作药物活性化合物。具体而言，式(I)的吡咯烷衍生物在治疗和/或预防早产、早产和痛经方面是有用的。特别地，本发明涉及显示出 oxytocin 受体的显著调节作用，特别是拮抗剂活性的吡咯烷衍生物。更优选地，所述化合物在治疗和/或预防由 oxytocin 介导的疾病状态，包括早产、早产和痛经方面是有用的。本发明还涉及新的吡咯烷衍生物以及它们的制备方法，其中 X 从 CR6R7、NOR6、NNR6R7 组中选择；A 从 —(C═O)—、—(C═O)—O—、—C(═NH)—、—(C═O)—NH—、—(C═S)—NH、—SO22-、—SO2NH—、—CH2- 组中选择；B 要么是一个 —(C═O)—NR8R9 组，要么表示具有式(a)的杂环残基，其中 Q 是 NR10、O 或 S；n 是选择的整数 0、1 或 2；Y、Z 和 E 与它们附着的 2 个碳一起形成一个 5-6 个成员的芳基或杂芳基环。
• TRANSGLUTAMINASE TG2 INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF
  申请人：DOMINGUEZ Celia

  公开号：US20150232420A1

  公开（公告）日：2015-08-20

  Certain compounds and pharmaceutically acceptable salts are provided herein. Also provided are pharmaceutical compositions comprising at least one compound or pharmaceutically acceptable salt therein and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain disease states responsive to the inhibition of transglutaminase TG2 activity are described. These disease states include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one compound or pharmaceutically acceptable salt thereof as a single active agent or administering at least one compound or pharmaceutically acceptable salt thereof in combination with one or more other therapeutic agents.

  本文提供了某些化合物和药用可接受盐。还提供了包含至少一种化合物或药用可接受盐和一个或多个药用可接受载体的药物组合物。描述了治疗对抑制转谷氨酰胺酶TG2活性有响应的某些疾病状态的方法。这些疾病状态包括亨廷顿病等神经退行性疾病。还描述了治疗方法，包括单独使用至少一种化合物或药用可接受盐作为活性剂或与一个或多个其他治疗剂联合使用至少一种化合物或药用可接受盐。