4-<<<3-hydroxy-2-methyl-5-<(phosphonooxy)methyl>-4-pyridynyl>methyl>amino>butanoic acid | 22342-63-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-<<<3-hydroxy-2-methyl-5-<(phosphonooxy)methyl>-4-pyridynyl>methyl>amino>butanoic acid
• 英文别名: 4-[({3-Hydroxy-2-Methyl-5-[(Phosphonooxy)methyl]pyridin-4-Yl}methyl)amino]butanoic Acid；4-[[3-hydroxy-2-methyl-5-(phosphonooxymethyl)pyridin-4-yl]methylamino]butanoic acid
• CAS: 22342-63-8
• 化学式: C₁₂H₁₉N₂O₇P
• 分子量: 334.266
• InChiKey: DOHWOHSLOVXAFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.6
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  149
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 4-<<<3-hydroxy-2-methyl-5-<(phosphonooxy)methyl>-4-pyridynyl>methyl>amino>butanoic acid 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以85%的产率得到4-(8-methyl-5-phosphonooxy)methyl-3,4-(dihydropyrido<4,3-e>-1,3-oxazin-3-yl)butanoic acid
  参考文献：
  名称：

  Transition-state analogues as inhibitors for GABA-aminotransferase

  摘要：

  Our previous calculations on the reaction catalysed by GABA-aminotransferase (GABA-T) have been utilized in this work in order to synthesize a series of reversible inhibitors of this enzyme. The synthesized transition-state analogues and their precursors inhibited GABA-T competitively in both the holoenzyme and apoenzyme at 10(-3) and 10(-5) M, respectively. In the case of the holoenzyme, the transition-state analogue series (the conformationally restricted series) gave a significant increase in inhibition values over the open (less conformationally restricted) series.

  DOI：

  10.1016/0223-5234(91)90022-f
• 作为产物：
  描述：

  磷酸吡哆醛 在 氢氧化钾 、 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.67h， 生成 4-<<<3-hydroxy-2-methyl-5-<(phosphonooxy)methyl>-4-pyridynyl>methyl>amino>butanoic acid
  参考文献：
  名称：

  Transition-state analogues as inhibitors for GABA-aminotransferase

  摘要：

  Our previous calculations on the reaction catalysed by GABA-aminotransferase (GABA-T) have been utilized in this work in order to synthesize a series of reversible inhibitors of this enzyme. The synthesized transition-state analogues and their precursors inhibited GABA-T competitively in both the holoenzyme and apoenzyme at 10(-3) and 10(-5) M, respectively. In the case of the holoenzyme, the transition-state analogue series (the conformationally restricted series) gave a significant increase in inhibition values over the open (less conformationally restricted) series.

  DOI：

  10.1016/0223-5234(91)90022-f

文献信息

• Preparation of prodrugs for selective drug delivery
  申请人：Mills L. Randell

  公开号：US20050080260A1

  公开（公告）日：2005-04-14

  Synthesis of a chemical compound having the formula A-B-C that may serve for applications such as drug delivery where A is a chemiluminescent, moiety, B is a photochromic moiety, and C is a biologically active moiety where A-B-C may serve as a prodrug. Novel synthetic methods of the present invention to form the prodrug comprised the steps of (1) forming a benzophenone, (2) forming a diaryl ethylene, (3) attaching a phthalimide moiety to at least one of the aryl groups of the ethylene to form a phthalimide-ethylene conjugate, (4) condensing two ethylene-phthalimide conjugates to form a phthalimide-pentadiene conjugate, (5) converting the phthalimide to the phthalhydrazide by reaction with hydrazine to form a carrier compound according to the present invention, and (6) reacting the carrier compound with an nucleophilic moiety of the drug to form the corresponding prodrug. Alternatively the carrier can be prepared by using the halo-substituted diaryl ethylene to make the corresponding cationic leuco dye-like compound with known methods. The cationic compound then is protected by reacting with a nucleophile and coupled with the aminophathalimide by palladium-catalyzed amination to form the protected phthalimide-pentadiene conjugate. The latter is refluxed with hydrazine to convert its phthalimide to the phthalhydrazide and acidified to give the carrier. An additional aspect of the present invention relates to the use of these compounds as antiviral agents for the treatment of viral infections such as HIV and as anticancer agents for the treatment of cancers such as bowel, lung, and breast cancer.

  合成具有A-B-C化学式的化合物，可用于药物传递等应用，其中A是化学发光基团，B是光致变色基团，C是生物活性基团，其中A-B-C可作为前药。本发明的新型合成方法用于形成前药，包括以下步骤：(1)形成苯酮，(2)形成二芳基乙烯，(3)将邻苯二甲酰亚胺基团连接到乙烯的至少一个芳基上，形成邻苯二甲酰亚胺-乙烯共轭物，(4)缩合两个乙烯-邻苯二甲酰亚胺共轭物，形成邻苯二甲酰亚胺-戊二烯共轭物，(5)通过与肼反应将邻苯二甲酰亚胺转化为邻苯二酰肼，形成本发明的载体化合物，(6)将载体化合物与药物的亲核基团反应，形成相应的前药。另外，可以通过使用卤代二芳基乙烯制备相应的阳离子类似的类似类似染料化合物。然后，通过与亲核试剂反应保护阳离子类似化合物，并通过钯催化的胺化与氨基邻苯二甲酰亚胺偶联，形成保护的邻苯二甲酰亚胺-戊二烯共轭物。后者与肼回流，将其邻苯二甲酰亚胺转化为邻苯二酰肼，并酸化以得到载体。本发明的另一个方面涉及将这些化合物用作抗病毒剂，用于治疗病毒感染，如HIV，以及用作抗癌剂，用于治疗结肠癌、肺癌和乳腺癌等癌症。
• Pro drugs for selective drug delivery
  申请人：——

  公开号：US20030228644A1

  公开（公告）日：2003-12-11

  Prodrug compounds capable of permeating a desired biological compartment and releasing a biologically active molecule in active form to effect a therapeutic functional change in the compartment to which it is introduced.

  原药化合物，能够渗透所需的生物区室，并以活性形式释放出生物活性分子，从而对所进入的生物区室产生治疗功能变化。
• [EN] LUMINIDE AND MACROLUMINIDE CLASS OF PHARMACEUTICALS
  申请人：MILLS, Randell, L.

  公开号：WO1989009833A1

  公开（公告）日：1989-10-19

  (EN) A broad class of pharmaceutical agents which react directly with electron carriers or with reactive species produced by electron transport to release a pharmacologically active molecule to effect a therapeutic functional change in the organism by a receptor or nonreceptor mediated action.(FR) On a mis au point une large catégorie d'agents pharmaceutiques réagissant directement avec des porteurs d'électrons ou avec des espèces réactives produites par transport d'électrons, pour libérer une molécule pharmacologiquement active, afin d'effectuer un changement fonctionnel thérapeutique dans l'organisme par une action provoquée par un récepteur ou sans récepteur.

  广泛的药用化学剂，它们直接与电子传递中的电子载体或与其他电子传递中产生的反应性物种相互作用，从而释放活性药物分子，以通过受体或非受体介导的方式在物体中产生治疗作用功能的治疗功能变化。(FR) 已开发并开始应用的一类广泛药物，它们可以直接与电子载体或与其他电子传递中产生的反应性物种相互作用，从而释放活性药物分子，以通过受体或非受体介导的方式在物体中产生治疗功能变化。
• EP0414730A4
  申请人：——

  公开号：EP0414730A4

  公开（公告）日：1993-06-16
• LUMINIDE AND MACROLUMINIDE CLASS OF PHARMACEUTICALS
  申请人：Mills, Randell L.

  公开号：EP0414730A1

  公开（公告）日：1991-03-06