(E)-ethyl 2-cyano-3-((cyanomethyl)(methoxycarbonyl)amino)acrylate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 乙烯基酰胺
• 英文名称: (E)-ethyl 2-cyano-3-((cyanomethyl)(methoxycarbonyl)amino)acrylate
• 英文别名: ethyl (E)-2-cyano-3-[cyanomethyl(methoxycarbonyl)amino]prop-2-enoate
• 化学式: C₁₀H₁₁N₃O₄
• 分子量: 237.215
• InChiKey: HHKQVPWMKCNMBM-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  103
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-ethyl 2-cyano-3-((cyanomethyl)(methoxycarbonyl)amino)acrylate 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 水 作用下， 以 二氯甲烷 、 甲醇 、 乙醇 为溶剂， 反应 2.25h， 生成 ethyl 4-amino-5-cyano-1H-pyrrole-3-carboxylate
  参考文献：
  名称：

  [EN] SALT AND POLYMORPHIC FORMS OF (3R,4S)-L-((4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)METHYL)-4(METHYLTHIOMETHYL)PYRODIN-3-OL(MTDIA)
  [FR] FORMES DE SEL ET FORMES POLYMORPHES DE (3R,4S)-1-((4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)METHYL)-4-(METHYLTHIOMETHYL)PYRROLIDIN-3-OL (MTDIA)

  摘要：

  该发明涉及(3R,4S)-1-((4-氨基-5H-吡咯并[3,2-d]嘧啶-7-基)甲基)-4-(甲硫甲基)吡咯烷-3-醇的盐形式，以及盐的多形式。该发明还涉及制备盐形式的过程，以及在治疗需要抑制5'-甲硫腺苷磷酸化酶（MTAP）的疾病和疾病时使用盐形式。

  公开号：

  WO2014073989A1
• 作为产物：
  描述：

  2-氰基-3-乙氧基丙烯酸乙酯 在 sodium acetate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 1.5h， 生成 (E)-ethyl 2-cyano-3-((cyanomethyl)(methoxycarbonyl)amino)acrylate
  参考文献：
  名称：

  Tight binding enantiomers of pre-clinical drug candidates

  摘要：

  MTDIA is a picomolar transition state analogue inhibitor of human methylthioadenosine phosphorylase and a femtomolar inhibitor of Escherichia coli methylthioadenosine nucleosidase. MTDIA has proven to be a non-toxic, orally available pre-clinical drug candidate with remarkable anti-tumour activity against a variety of human cancers in mouse xenografts. The structurally similar compound MTDIH is a potent inhibitor of human and malarial purine nucleoside phosphorylase (PNP) as well as the newly discovered enzyme, methylthioinosine phosphorylase, isolated from Pseudomonas aeruginosa. Since the enantiomers of some pharmaceuticals have revealed surprising biological activities, the enantiomers of MTDIH and MTDIA, compounds 1 and 2, respectively, were prepared and their enzyme binding properties studied. Despite binding less tightly to their target enzymes than their enantiomers compounds 1 and 2 are nanomolar inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.059

文献信息

• [EN] SALT AND POLYMORPHIC FORMS OF (3R,4S)-L-((4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)METHYL)-4(METHYLTHIOMETHYL)PYRODIN-3-OL(MTDIA)<br/>[FR] FORMES DE SEL ET FORMES POLYMORPHES DE (3R,4S)-1-((4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)METHYL)-4-(METHYLTHIOMETHYL)PYRROLIDIN-3-OL (MTDIA)
  申请人：CALLAGHAN INNOVATION RES LTD

  公开号：WO2014073989A1

  公开（公告）日：2014-05-15

  The invention relates to salt forms of (3R,4S)-1-((4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl)-4-(methylthiomethyl)pyrrolidin-3-ol, as well as polymorphic forms of the salts. The invention further relates to processes for preparing the salt forms and to the use of the salt forms in the treatment of diseases and disorders where it is desirable to inhibit 5'-methylthioadenosine phosphorylase (MTAP).

  该发明涉及(3R,4S)-1-((4-氨基-5H-吡咯并[3,2-d]嘧啶-7-基)甲基)-4-(甲硫甲基)吡咯烷-3-醇的盐形式，以及盐的多形式。该发明还涉及制备盐形式的过程，以及在治疗需要抑制5'-甲硫腺苷磷酸化酶（MTAP）的疾病和疾病时使用盐形式。
• SALT AND POLYMORPHIC FORMS OF (3R,4S)-L-((4-AMINO-5H-PYRROLO[3,2,-D]PYRIMIDIN-7-YL)METHYL)-4(METHYLTHIOMETHYL)PYRODIN-3-OL(MTDIA)
  申请人：Victoria Link Limited

  公开号：US20150274741A1

  公开（公告）日：2015-10-01

  The invention relates to salt forms of (3R,4S)-1-((4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl)-4-(methyl-thiomethyl)pyrrolidin-3-ol, as well as polymorphic forms of the salts. The invention further relates to processes for preparing the salt forms and to the use of the salt forms in the treatment of diseases and disorders where it is desirable to inhibit 5′-methylthioadenosine phosphorylase (MTAP).

  本发明涉及（3R，4S）-1-（（4-氨基-5H-吡咯并[3,2-d]嘧啶-7-基）甲基）-4-（甲硫甲基）吡咯烷-3-醇的盐形式，以及盐的多形式。本发明还涉及制备盐形式的过程，并且涉及在治疗希望抑制5'-甲基硫腺苷磷酸化酶（MTAP）的疾病和疾病中使用盐形式。
• SALT AND POLYMORPHIC FORMS OF (3R,4S)-L-((4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)METHYL)-4(METHYLTHIOMETHYL)PYRROLIDIN-3-OL(MTDIA)
  申请人：Victoria Link Limited

  公开号：EP3527554A2

  公开（公告）日：2019-08-21

  The invention relates to a process for the preparation of the phosphate salt of (3R,4S)-1-((4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl)-4-(methylthiomethyl)pyrrolidin-3-ol (MTDIA), and to processes for making certain intermediate compounds which are used therein.

  本发明涉及一种制备(3R,4S)-1-((4-氨基-5H-吡咯并[3,2-d]嘧啶-7-基)甲基)-4-(甲硫基甲基)吡咯烷-3-醇（MTDIA）的磷酸酯盐的工艺，以及制备其中使用的某些中间体化合物的工艺。
• Salt and polymorphic forms of (3R,4S)-L-((4-amino-5H-pyrrolo[3,2,-D]pyrimidin-7-yl)methyl)-4(methylthiomethyl)pyrodin-3-ol(MTDIA)
  申请人：VICTORIA LINK LIMITED

  公开号：US10227351B2

  公开（公告）日：2019-03-12

  The invention relates to salt forms of (3R,4S)-1-((4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl)-4-(methyl-thiomethyl)pyrrolidin-3-ol, as well as polymorphic forms of the salts. The invention further relates to processes for preparing the salt forms and to the use of the salt forms in the treatment of diseases and disorders where it is desirable to inhibit 5′-methylthioadenosine phosphorylase (MTAP).

  本发明涉及(3R,4S)-1-((4-氨基-5H-吡咯并[3,2-d]嘧啶-7-基)甲基)-4-(甲硫基甲基)吡咯烷-3-醇的盐形式以及这些盐的多晶型形式。本发明进一步涉及制备盐形式的工艺以及盐形式在治疗希望抑制 5′-甲硫基腺苷磷酸化酶（MTAP）的疾病和失调中的用途。
• US9994574B2
  申请人：——

  公开号：US9994574B2

  公开（公告）日：2018-06-12