7-methoxycarbonylpterin | 31010-69-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 英文名称: 7-methoxycarbonylpterin
• 英文别名: methyl 2-amino-4-oxo-3H-pteridine-7-carboxylate
• CAS: 31010-69-2
• 化学式: C₈H₇N₅O₃
• 分子量: 221.175
• InChiKey: RTDPOAURCGIJLL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-methoxycarbonylpterin 在 copper(ll) sulfate pentahydrate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 sodium ascorbate 作用下， 以 甲醇 、 水 、 叔丁醇 为溶剂， 反应 48.0h， 生成 N-((1-(naphthalen-1-ylmethyl)-1H-1,2,3-triazol-4-yl)methyl)pterin-7-carboxamide
  参考文献：
  名称：

  Optimized 5-Membered Heterocycle-Linked Pterins for the Inhibition of Ricin Toxin A

  摘要：

  The optimization of a series of pterin amides for use as Ricin Toxin A (RTA) inhibitors is reported. On the basis of crystallographic data of a previous furan-linked pterin, various expanded furans were synthesized, linked to the pterin, and tested for inhibition. Concurrently, heteroanalogues of furan were explored, leading to the discovery of more potent triazole-linked pterins. Additionally, we discuss a dramatic improvement in the synthesis of these pterin amides via a dual role by diazabicycloundecene (DBU). This synthetic enhancement facilitates rapid diversification of the previously challenging pterin heterocycle, potentially aiding future medicinal research involving this structure.

  DOI：

  10.1021/ml300099t
• 作为产物：
  描述：

  丙酮酸甲酯 、 2-氨基-4-羟基蝶啶 在 硫酸 、 双氧水 作用下， 以 水 为溶剂， 生成 7-methoxycarbonylpterin
  参考文献：
  名称：

  Pterin-7-羧酰胺类是新型的醛糖还原酶抑制剂

  摘要：

  醛糖还原酶与糖尿病并发症如神经病变，视网膜病变，血管病变等的发生和发展有关：因此，能够抑制该酶的分子是治疗糖尿病并发症的潜在药物。Epalrestat是临床上唯一的醛糖还原酶抑制剂，但仍存在一些缺点。因此，仍然需要开发新的醛糖还原酶抑制剂。我们已经合成了一系列新的pterin-7-羧酰胺，并评估了它们对人醛糖还原酶的体外抑制活性。所有新合成的化合物均表现出抑制活性。其中1a具有甘氨酸侧链的具有最高活性的可与山梨醇（一种高活性的醛糖还原酶抑制剂）相媲美。1a在酶的活性位点上的分子对接表明该化合物与对该酶特异并与抑制副作用有关的氨基酸残基相互作用。根据这些结果，我们证明了perin-7-羧酰胺是一类新型的醛糖还原酶抑制剂，尤其是化合物1a被认为是治疗糖尿病并发症副作用少的药物，是进行进一步生物学研究的良好候选者。

  DOI：

  10.1016/j.bmcl.2016.09.033

文献信息

• Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin
  作者：Anna R Bockman、Jeffrey M Pruet

  DOI：10.3762/bjoc.16.46

  日期：——

  medicinally relevant pteridine derivatives. Reactions which expedite the development of new pterins are thus of great importance. Through a dual role of diazabicycloundecene (DBU), 7-carboxymethylpterin is converted to the soluble DBU salt, with additional DBU promoting an ester-to-amide transformation. We have explored this reaction to assess its scope and identify structural features in the amines

  蝶呤的合成效用常常受到该杂环臭名昭著的不溶性的阻碍，从而减缓了与医学相关的蝶啶衍生物的开发。因此，加速新蝶呤开发的反应非常重要。通过二氮杂双环十一碳烯（DBU）的双重作用，将7-羧甲基蝶呤转化为可溶性DBU盐，另外的DBU促进了酯到酰胺的转化。我们已经研究了该反应以评估其范围并确定对胺有重大影响的结构特征，使用拟一级动力学模型监控了反应动力学，并进一步调整了反应条件以使产物形成少至5分钟，收率通常> 80％。
• Pterin-based small molecule inhibitor capable of binding to the secondary pocket in the active site of ricin-toxin A chain
  作者：Ryota Saito、Masaru Goto、Shun Katakura、Taro Ohba、Rena Kawata、Kazuki Nagatsu、Shoko Higashi、Kaede Kurisu、Kaori Matsumoto、Kouta Ohtsuka

  DOI：10.1371/journal.pone.0277770

  日期：——

  adenine base at a specific region of the ribosome leading to death, has two adjacent specificity pockets in its active site. Based on this structural information, many attempts have been made to develop small-molecule RTA inhibitors that simultaneously block the two pockets. However, no attempt has been successful. In the present study, we synthesized pterin-7-carboxamides with tripeptide pendants and found

  蓖麻毒素 A 链 (RTA) 在核糖体特定区域的腺嘌呤碱基脱嘌呤并导致死亡，其活性位点有两个相邻的特异性口袋。基于这一结构信息，人们进行了许多尝试来开发同时阻断两个口袋的小分子 RTA 抑制剂。然而，没有任何尝试成功。在本研究中，我们合成了带有三肽悬挂物的蝶呤-7-甲酰胺，发现其中之一同时与两个口袋相互作用，表现出良好的RTA抑制活性。对含有新型抑制剂的 RTA 晶体进行 X 射线晶体分析表明，Tyr80 的构象变化是抑制剂同时堵塞两个口袋的重要因素。
• Sulfur incorporation generally improves Ricin inhibition in pterin-appended glycine-phenylalanine dipeptide mimics
  作者：Paul A. Wiget、Lawrence A. Manzano、Jeff M. Pruet、Grace Gao、Ryota Saito、Arthur F. Monzingo、Karl R. Jasheway、Jon D. Robertus、Eric V. Anslyn

  DOI：10.1016/j.bmcl.2013.10.017

  日期：2013.12

  Several 7-aminoamido-pterins were synthesized to evaluate the electronic and biochemical subtleties observed in the 'linker space' when N-N-(pterin-7-yl)carbonylglycyl}-l-phenylalanine 1 was bound to the active site of RTA. The gylcine-phenylalanine dipeptide analogs included both amides and thioamides. Decarboxy gly-phe analog 2 showed a 6.4-fold decrease in potency (IC50 = 128 μM), yet the analogous thioamide 7 recovered the lost activity and performed similarly to the parent inhibitor (IC50 = 29 μM). Thiourea 12 exhibited an IC50 nearly six times lower than the oxo analog 13. All inhibitors showed the pterin head-group firmly bound in their X-ray structures yet the pendants were not fully resolved suggesting that all pendants are not firmly bound in the RTA linker space. Calculated log P values do not correlate to the increase in bioactivity suggesting other factors dominate.
• 7-Substituted pterins provide a new direction for ricin A chain inhibitors
  作者：Jeff M. Pruet、Karl R. Jasheway、Lawrence A. Manzano、Yan Bai、Eric V. Anslyn、Jon D. Robertus

  DOI：10.1016/j.ejmech.2011.05.025

  日期：2011.9

  Ricin is a potent toxin found in castor seeds. The A chain, RTA, enzymaticlly depurinates a specific adenosine in ribosomal RNA, inhibiting protein synthesis. Ricin is a known chemical weapons threat having no effective antidote. This makes the discovery of new inhibitors of great importance. We have previously used 6-substituted pterins, such as pteroic acid, as an inhibitor platform with moderate success. We now report the success of 7-carboxy pterin (7CP) as an RTA inhibitor; its binding has been monitored using both kinetic and temperature shift assays and by X-ray crystallography. We also discuss the synthesis of various derivatives of 7CP, and their binding affinity and inhibitory effects, as part of a program to make effective RTA inhibitors. Published by Elsevier Masson SAS.
• Peptide-Conjugated Pterins as Inhibitors of Ricin Toxin A
  作者：Ryota Saito、Jeff M. Pruet、Lawrence A. Manzano、Karl Jasheway、Arthur F. Monzingo、Paul A. Wiget、Ishan Kamat、Eric V. Anslyn、Jon D. Robertus

  DOI：10.1021/jm3016393

  日期：2013.1.10

  Several 7-peptide-substituted pterins were synthesized and tested as competitive active-site inhibitors of ricin toxin A (RTA). Focus began on dipeptide conjugates, and these results further guided the construction of several tripeptide conjugates. The binding of these compounds to RTA was studied via a luminescence-based kinetic assay, as well as through X-ray crystallography. Despite the relatively polar, solvent exposed active site, several hydrophobic interactions, most commonly π-interactions not predicted by modeling programs, were identified in all of the best-performing inhibitors. Nearly all of these compounds provide IC₅₀ values in the low micromolar range.