Coformycin | 11033-22-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Coformycin
• 英文别名: (2R,3R,4S,5R)-2-[(8R)-8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 11033-22-0
• 化学式: C₁₁H₁₆N₄O₅
• 分子量: 284.27
• InChiKey: YOOVTUPUBVHMPG-LODYRLCVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  132
• 氢给体数：
  5
• 氢受体数：
  7

制备方法与用途

生物活性

Coformycin 是一种核苷类抗生素，是腺苷脱氨酶 (adenosine deaminase, ADA) 的抑制剂。它具有抗肿瘤和抗菌活性。

体内研究

Coformycin 在每天腹腔注射 0.2 mg/kg 后，能够抑制多种组织的腺苷脱氨酶活性，包括大脑、心脏、肾脏和肝脏等。

实验结果如下：

• 动物模型: Swiss-Webster 小鼠
• 剂量: 0.2 mg/kg
• 给药方式: 每天腹腔注射
• 结果: 抑制了多种组织的腺苷脱氨酶活性

反应信息

• 作为反应物：
  描述：

  Coformycin 、 5-amino-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)imidazole-4-carboxylic acid 以to produce 3-(β-D-ribofuranosyl)-6,7-dihydroimidazo[4,5-d][1,3]diazepin-8(3H)-one as an intermediate的产率得到Dehydrocoformycin
  参考文献：
  名称：

  Process for the preparation of 2'-deoxy-2'-halocoformycins or

  摘要：

  本发明的目的是提供一种新型合成2'-脱氧-2'-卤代甲霉素的方法，其在实际上具有高收率的抑制腺苷脱氨酶的活性。因此，提供了一种包括多级反应的过程，使用tert-丁基1-（3,5-二-O-酰基-2-脱氧-2-卤代-β-D-核糖或阿拉伯核糖）-5-氨基咪唑-4-羧酸酯（式（II））作为起始中间体，从而产生2'-脱氧-2'-卤代甲霉素或2'-脱氧-2'-表-2'-卤代甲霉素（式（I-a））以及2'-脱氧-8-表-2'-卤代甲霉素或2'-脱氧-8,2'-二表-2'-卤代甲霉素（式（I-b））的方法。预计2'-脱氧-2'-卤代甲霉素及其表异构体可用作淋巴细胞白血病药物以及各种由腺苷脱氨酶作用引起的疾病的药物。

  公开号：

  US05831072A1

文献信息

• INDAZOLE DERIVATIVES AS ADENOSINE MONOPHOSPHATE DEAMINASE (AMPD) INHIBITORS FOR USE IN DIABETES AND RELATED DISEASES OF METABOLIC SYNDROME
  申请人：Ochs Raymond S.

  公开号：US20120130078A1

  公开（公告）日：2012-05-24

  Herein, we describe a method for treatment of diabetes and other disorders classified as Metabolic Syndrome. The invention provides novel AMP Deaminase (AMPD) inhibitors comprising novel indazole and benzotriazole derivatives including a phosphorous containing derivative, a carboxylic acid, or an amino acid ester prodrug. The invention also provides support for a novel mechanism of action for the existing drug metformin: direct inhibition of the enzyme AMPD. The inhibition of AMPD in turn activates AMP Kinase, known to be linked to the action of metformin. The invention also makes novel use of a double inhibitor assay allowing identification of selective AMPD inhibitors over ADA inhibitors. The new inhibitors, structurally distinct from metformin, offer selectivity that may obviate side effects known for metformin itself, providing new benefits for diabetes and Metabolic Syndrome.

  在这里，我们描述了一种治疗糖尿病和其他归类为代谢综合征的疾病的方法。该发明提供了一种新型的AMP脱氨酶（AMPD）抑制剂，包括新型的吲唑和苯并三唑衍生物，其中包括含磷衍生物、羧酸或氨基酸酯前药。该发明还支持现有药物二甲双胍的一种新颖作用机制：直接抑制AMPD酶。抑制AMPD反过来激活AMP激酶，已知与二甲双胍的作用有关。该发明还首次使用了一种双重抑制剂分析，允许识别对ADA抑制剂具有选择性的AMPD抑制剂。这些新抑制剂在结构上与二甲双胍不同，提供的选择性可能消除二甲双胍本身已知的副作用，为糖尿病和代谢综合征带来新的益处。
• Stem Cell Culture Methods
  申请人：Adams David Roger

  公开号：US20120202287A1

  公开（公告）日：2012-08-09

  The invention provides methods for reversibly inhibiting stem cell differentiation wherein a compound of formula (I) is contacted with a stem cell. The invention further provides a method for preparing a culture medium, a culture medium supplement and a composition comprising a compound of formula (I).

  该发明提供了一种可逆抑制干细胞分化的方法，其中将式(I)的化合物与干细胞接触。该发明还提供了一种制备培养基、培养基添加剂和包含式(I)化合物的组合物的方法。
• Process for the production of pentostatin aglycone and pentostatin
  申请人：——

  公开号：US20040181052A1

  公开（公告）日：2004-09-16

  A novel, scaleable and improved process for preparing pentostatin and its analogs is disclosed. The method comprises the diastereospecific synthesis of the nucleobase from commercially available L-Dialkyl tartarates.

  揭示了一种用于制备戊糖核苷和其类似物的新型、可扩展和改进的工艺。该方法包括从市售的L-二烷基酒石酸盐合成核碱的对映体特异性合成。
• 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。
• [EN] ANTI-VIRAL AND HEPATIC-TARGETED DRUGS<br/>[FR] MÉDICAMENTS ANTIVIRAUX ET CIBLÉS SUR LE FOIE
  申请人：AI BIOPHARMA

  公开号：WO2021074443A1

  公开（公告）日：2021-04-22

  Disclosed herein are identified compound fragments, compounds and their pharmaceutically acceptable salts, isotopes or solvates, useful as antiviral drug and/or as a hepatic-targeted drug, such as for the treatment of HBV, HDV and/or HIV. Formula (I).

  本文揭示了被识别的化合物片段、化合物及其药学上可接受的盐、同位素或溶剂化合物，用作抗病毒药物和/或肝靶向药物，例如用于治疗HBV、HDV和/或HIV。公式（I）。