α-Acetylen-α,δ-diaminovaleriansaeure | 67605-54-3

• 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: α-Acetylen-α,δ-diaminovaleriansaeure
• 英文别名: 2-ethynyl-2-amino-5-aminopentanoic acid；2,5-diamino-2-(ethynyl)pentanoic acid；alpha-Ethynyl-alpha,delta-diaminovaleric acid；2,5-diamino-2-ethynylpentanoic acid
• CAS: 67605-54-3；111656-45-2；111714-49-9
• 化学式: C₇H₁₂N₂O₂
• 分子量: 156.184
• InChiKey: JWWZUFCRQMJENK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  89.3
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 sodium hydroxide 、 碘代三甲硅烷 、 三乙胺 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 13.0h， 生成 α-Acetylen-α,δ-diaminovaleriansaeure
  参考文献：
  名称：

  .alpha.-Ethynyl and .alpha.-vinyl analogs of ornithine as enzyme-activated inhibitors of mammalian ornithine decarboxylase

  摘要：

  alpha-Ethynyl- and alpha-vinylornithine were designed and synthesized as potential enzyme-activated inhibitors of mammalian ornithine decarboxylase. These two new inhibitors produce both immediate and time-dependent inhibition of rat liver ornithine decarboxylase in vitro. The inhibitions exhibition saturation kinetics. The apparent dissociation constants (KI) are 10 and 810 microM, and the times of half-inactivation at infinite concentration of inhibitor (t1/2) are 8.5 and 27 min, respectively, for alpha-ethynyl- and alpha-vinylornithine. In rats, alpha-ethynylornithine causes a rapid dose-dependent decrease of ornithine decarboxylase activity in prostate and, to a lesser extent, in thymus and testis.

  DOI：

  10.1021/jm00133a005

文献信息

• S-Adenosylmethionine decarboxylase inhibitors
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：EP0351475A1

  公开（公告）日：1990-01-24

  This invention relates to novel chemical compounds useful as S-adenosylmethionine decarboxylase inhibitors, of the formula H₂N-Q--Al wherein Al represents 5'-deoxyadenosyl.      represents adenosinyl, R represents H, methyl or ethyl and Q represents moieties of formulae Ia to If depicted as follows: wherein R₁ is H or F, n is 1 or 2, V₁ is H or CH₃, V₂ is H or COOH, and each of W, X, Y, and Z are H, F, Cl or Br. To the processes useful for their preperation and to their use in the treatment of a variety of condition and disease states associated with a rapid proliferation of cell growth.

  这项发明涉及一种新型化合物，可用作S-腺苷甲硫氨酸脱羧酶抑制剂，其化学式为H₂N-Q--Al，其中Al代表5'-去氧腺苷基。     代表腺苷基，R代表H、甲基或乙基，Q代表如下所示的化学式Ia至If的基团：其中R₁为H或F，n为1或2，V₁为H或CH₃，V₂为H或COOH，而W、X、Y和Z中的每一个均为H、F、Cl或Br。还涉及用于其制备的方法以及它们在治疗与细胞增殖快速增加相关的各种疾病和病症中的应用。
• Renal-selective prodrugs for control of renal sympathetic nerve activity in the treatment of hypertension
  申请人：G.D. Searle & Co.

  公开号：US20030220521A1

  公开（公告）日：2003-11-27

  Renal-selective prodrugs are described which are preferentially converted in the kidney to compounds capable of inhibiting synthesis of catecholamine-type neurotransmitters involved in renal sympathetic nerve activity. The prodrugs described herein are derived from inhibitor compounds capable of inhibiting one or more of the enzymes involved in catecholamine synthesis, such compounds being classifiable as tyrosine hydroxylase inhibitors, or as dopa-decarboxylase inhibitors, or as dopamine-&bgr;-hydroxylase inhibitors. These inhibitor compounds are linked to a chemical moiety, such as a glutamic acid derivative, by a cleavable bond which is recognized selectively by enzymes located predominantly in the kidney. The liberated inhibitor compound is then available in the kidney to inhibit one or more of the enzymes involved in catecholamine synthesis. Inhibition of renal catecholamine synthesis can suppress heightened renal nerve activity associated with sodium-retention related disorders such as hypertension. Conjugates of particular interest are glutamyl derivatives of dopamine-&bgr;-hydroxylase inhibitors, of which N-acetyl-&ggr;-glutamyl fusaric acid hydrazide (shown below) is preferred. 1

  本文描述了一种肾选择性的前药，其在肾脏中优先转化为能够抑制参与肾交感神经活动的儿茶酚型神经递质合成的化合物。本文所描述的前药来源于能够抑制儿茶酚合成中的一个或多个酶的抑制剂化合物，这些化合物可分类为酪氨酸羟化酶抑制剂，多巴脱羧酶抑制剂或多巴胺-&bgr;-羟化酶抑制剂。这些抑制剂化合物通过可被肾脏中大量存在的酶选择性识别的可裂解键与化学基团（如谷氨酸衍生物）连接。释放的抑制剂化合物然后可在肾脏中用于抑制儿茶酚合成中的一个或多个酶。抑制肾脏儿茶酚合成可抑制与钠潴留相关的疾病（如高血压）相关的增强肾脏神经活动。特别感兴趣的共轭物是多巴胺-&bgr;-羟化酶抑制剂的谷氨酰衍生物，其中N-乙酰-&ggr;-谷氨酰富萨酸肼（如下图所示）是首选。1
• Renal-selective prodrugs for control of renal smpathetic nerve activity in the treatment of hypertension
  申请人：G.D. Searle & Co.

  公开号：US20040101523A1

  公开（公告）日：2004-05-27

  Renal-selective prodrugs are described which are preferentially converted in the kidney to compounds capable of inhibiting synthesis of catecholamine-type neurotransmitters involved in renal sympathetic nerve activity. The prodrugs described herein are derived from inhibitor compounds capable of inhibiting one or more of the enzymes involved in catecholamine synthesis, such compounds being classifiable as tyrosine hydroxylase inhibitors, or as dopa-decarboxylase inhibitors, or as dopamine-&bgr;-hydroxylase inhibitors. These inhibitor compounds are linked to a chemical moiety, such as a glutamic acid derivative, by a cleavable bond which is recognized selectively by enzymes located predominantly in the kidney. The liberated inhibitor compound is then available in the kidney to inhibit one or more of the enzymes involved in catecholamine synthesis. Inhibition of renal catecholamine synthesis can suppress heightened renal nerve activity associated with sodium-retention related disorders such as hypertension. Conjugates of particular interest are glutamyl derivatives of dopamine-&bgr;-hydroxylase inhibitors, of which N-acetyl-&ggr;-glutamyl fusaric acid hydrazide (shown below) is preferred. 1

  本文描述了肾脏选择性前药，这些前药被优先转化为能够抑制与肾脏交感神经活动相关的儿茶酚类神经递质合成的化合物。所述前药源自能够抑制儿茶酚类合成中涉及的一个或多个酶的抑制剂化合物，这些化合物可分类为酪氨酸羟化酶抑制剂，或多巴脱羧酶抑制剂，或是多巴胺-β-羟化酶抑制剂。这些抑制剂化合物与化学基团（例如谷氨酸衍生物）通过可被肾脏内的酶特异性识别的可切断键连接。被释放的抑制剂化合物随后可在肾脏中抑制一个或多个涉及儿茶酚类合成的酶。抑制肾脏儿茶酚类合成可以抑制与钠潴留相关的疾病（如高血压）所伴随的过度肾脏神经活动。特别感兴趣的结合物是多巴胺-β-羟化酶抑制剂的谷氨酰衍生物，其中N-乙酰-γ-谷氨酰菌核酸酸肼（如下图所示）是首选。1
• Method of inhibiting algae
  申请人：Merrell Dow Pharmaceuticals Inc.

  公开号：US04336054A1

  公开（公告）日：1982-06-22

  .alpha.-Substituted amines and .alpha.-substituted-.alpha.-amino acids are described which are useful in controlling the growth of algae.

  本文描述了有用于控制藻类生长的.alpha.-取代胺和.alpha.-取代-.alpha.-氨基酸。
• D-enantiomer of DFMO and methods of use therefor
  申请人：ILEX Oncology, Inc.

  公开号：US20020045663A1

  公开（公告）日：2002-04-18

  The present invention concerns a method for preventing and/or treating cancer in a patient comprising administering an effective amount of substantially purified D enantiomer of difluoromethylornithine (D-DFMO) or an analog of D-DFMO to the patient. D-DFMO or an analog thereof is administered at a dose of about 0.05 to about 20.0 gm/M 2 /day. D-DFMO or an analog thereof may be administered more than once for the treatment and/or prevention of cancer. Methods of administration as well as compositions and formulations of substantially purified D-DFMO and analogs of D-DFMO are described.

  本发明涉及一种预防和/或治疗患者癌症的方法，包括向患者施用有效量的基本纯化的二氟甲基鸟氨酸D对映体（D-DFMO）或D-DFMO类似物。D-DFMO或其类似物的给药剂量约为0.05至约20.0 gm/M 2 /天。D-DFMO或其类似物可多次给药，用于治疗和/或预防癌症。本文描述了基本纯化的 D-DFMO 和 D-DFMO 类似物的给药方法以及组合物和制剂。